Teza - Modelling and Control of The Human

Master Thesis
Modelling and control of the human

cardiovascular system
Stefan Gisler
Advisers
Martin Wieser and Dr. Heike Vallery
and
Prof. Dr. Robert Riener
Sensory Motor Systems Lab (SMS)
Swiss Federal Institute of Technology Zurich (ETH)
Submission: April 2011

Contents
1 Introduction 1
2 Human cardiovascular system 5

2.1 Hemodynamic system . . . . . . . . . . . . . . . . . . . . . . . 5
2.2 Blood pressure regulation . . . . . . . . . . . . . . . . . . . . 7
2.3 Orthostatic reaction and muscle pump . . . . . . . . . . . . . 9
2.4 Cardiovascular pathology . . . . . . . . . . . . . . . . . . . . . 10
2.5 Literature review . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.5.1 Cardiovascular responses to passive tilting . . . . . . . 11
2.5.2 Cardiovascular modelling . . . . . . . . . . . . . . . . . 13
3 Cardiovascular model 15
3.1 Hemodynamic system . . . . . . . . . . . . . . . . . . . . . . . 16
3.2 Blood pressure regulation . . . . . . . . . . . . . . . . . . . . 18
3.3 Influence of gravity . . . . . . . . . . . . . . . . . . . . . . . . 21
3.4 Influence of stepping . . . . . . . . . . . . . . . . . . . . . . . 22
3.5 Model simulations . . . . . . . . . . . . . . . . . . . . . . . . . 24
3.5.1 Fast tilt-up and tilt-down . . . . . . . . . . . . . . . . 24
3.5.2 Stepping . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.5.3 Quasi-static . . . . . . . . . . . . . . . . . . . . . . . . 26
3.6 Model validation . . . . . . . . . . . . . . . . . . . . . . . . . 33
4 Control design 37
4.1 Model predictive control (MPC) design . . . . . . . . . . . . . 37
4.2 Simulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
5 Methods 49
5.1 Healthy subjects . . . . . . . . . . . . . . . . . . . . . . . . . 49
5.1.1 Implementation . . . . . . . . . . . . . . . . . . . . . . 49
5.1.2 Blood pressure recording . . . . . . . . . . . . . . . . . 49
5.1.3 Experimental design . . . . . . . . . . . . . . . . . . . 50
i
5.2 Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
5.2.1 Implementation . . . . . . . . . . . . . . . . . . . . . . 53
5.2.2 Blood pressure recording . . . . . . . . . . . . . . . . . 53
5.2.3 Experimental design . . . . . . . . . . . . . . . . . . . 54
6 Results 55
6.1 Healthy subjects . . . . . . . . . . . . . . . . . . . . . . . . . 55
6.1.1 Heart rate control . . . . . . . . . . . . . . . . . . . . . 55
6.1.2 Blood pressure control . . . . . . . . . . . . . . . . . . 55
6.1.3 Combined heart rate and blood pressure control . . . . 56
6.2 Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
6.3 Controller performance . . . . . . . . . . . . . . . . . . . . . . 60
7 Discussion 61
8 Conclusion and Outlook 65
A Model summary 73
A.1 List of variables . . . . . . . . . . . . . . . . . . . . . . . . . . 75
A.2 List of parameters . . . . . . . . . . . . . . . . . . . . . . . . . 76
A.3 Model equations in non-linear state-space form . . . . . . . . . 78
A.4 Steady-state equations in non-linear state-space form . . . . . 80
A.5 Parameter identification . . . . . . . . . . . . . . . . . . . . . 82
A.6 Model constraints . . . . . . . . . . . . . . . . . . . . . . . . . 85
B Summarised results 87
References 95
ii
Abstract
Bed-rest leads to cardiovascular deconditioning and may induce a decline in
stroke volume, cardiac output and oxygen uptake. Further, it increases the
risk of orthostatic intolerance. In an early phase of rehabilitation, it is there-
fore important to prevent the development of cardiovascular deconditioning
which can be done by verticalisation and mobilisation. In the future, the
enhanced ERIGO tilt-table will be able to control physiological signals and
hence, stabilise the patients cardiovascular system.
This thesis focuses on the control of heart rate and blood pressure by means
of verticalisation (tilting) and mobilisation (stepping). In a first step, a car-
diovascular non-linear model with two inputs (tilting and stepping) and three
outputs (heart rate, systolic and diastolic blood pressure) is developed based
on physiological principles and existing work. The model is then used for
designing a model predictive controller which was found well suited for the
given control problem.
Five healthy subjects have been tested with three different configurations:
isolated heart rate control, isolated blood pressure control and combined
control. One patient has been tested with blood pressure control which yiel-
ded promising results.
Keywords Orthostatic intolerance, cardiovascular modelling, model pre-

dictive control
iii
Acknowledgements
First, I want to thank Prof. Dr. Riener for being accepted to do this thesis at
the Sensory-Motor Systems Lab. Then I want to thank my advisers Martin
Wieser and Dr. Heike Vallery for their valuable support during the work.
Special thanks go to Martin Wieser for his great efforts while testing and
debugging the system.
This thesis would not have been possible without the probands and patients.
A big thanks goes to all the probands, the Z urcher Hohenklinik in Wald,
and all the patients that participated in this study. At this point, I also want
to thank Rafael R ust and Lilith Butler for their support during the patient
measurements in Wald.
Last but not least, I want to thank all the students in the student room for
the nice and inspiring atmosphere.
iv
Chapter 1
Introduction
One major problem with neurological patients suffering from stroke, trau-
matic brain injury or paraplegia is the long bed rest after the accident. It
leads to deconditioning of the patients cardiovascular system and evokes
secondary complications such as orthostatic intolerance. Further complica-
tions can include venous thrombosis, muscle atrophy, joint contractures and
osteoporosis [1], [2]. Therefore, early mobilisation of the patient is crucial as
it can reduce the risk of cardiovascular deconditiong and improves the state
of health.
This thesis focuses on the cardiovascular aspects of bed-ridden patients, i.e.

how the cardiovascular system can be prevented from deconditioning and be-
coming unstable. Prolonged bed rest leads to a decrease in circulating blood
volume, a decrease in stroke volume and pulse pressure, and an increased
heart rate. A direct result of these indications is the inability of the patients
cardiovascular system to regulate blood pressure when standing up (ortho-
static intolerance). In the upright position, the patient suddenly starts to
feel dizzy or even faints due to excessive blood pooling in the lower extre-
mities and reduced blood perfusion of the upper body. However, orthostatic
intolerance is not only caused by prolonged bedrest but can also be a conse-
quence of an impaired vegetative nervous system. In paraplegia patients,
the sympathetic effector nerves to the heart and the smooth musculature are
disrupted or even broken. This leads to a malfunction of the baroreflex which
is responsible for regulating arterial blood pressure (see chapters 2.2, 2.4).
As a consequence, the sudden decrease in arterial blood pressure cannot be
regulated and the patient faints.
A tilt-table therapy is aimed at reconditioning the patients cardiovascular

system by verticalising to an angle of about 80 degrees. Additional leg mo-
1
vements which can include stepping or cycling movements increase venous
return due to the effects of the muscle pump and improve orthostatic tole-
rance. The ERIGO device which has been used at the institute since the
beginning of the AwaCon project combines these therapies and allows for an
optimal treatment of patients with neurological disorders (Figure 1.1). More
information about the ERIGO device can be found on the homepage of HO-
COMA AG 1 . On the ERIGO, physiological signals such as blood pressure,
Figure 1.1: Left: Schematic representation of the ERIGO device with the
three inputs. Right: ERIGO during therapy session.
heart rate, respiration frequency, skin conductance, oxygen saturation, EEG

and EMG can be recorded. However, for this thesis only blood pressure and
heart rate need to be recorded, where EMG recordings may be helpful to
analyse muscle activity during mobilisation.
The goal of the project is to control and stabilise the cardiovascular system
of patients with neurological disorders by verticalisation, mobilisation and
cyclic loading of the lower limbs (Figure 1.1). This will help to improve the
cardiovascular status of these patients and will have the potential to reduce
medication, enhance physiotherapy and shorten the duration of early reha-
bilitation [3]. Furthermore, the risk of deconditioning of the cardiovascular
system, and complications resulting from this, can be decreased. Additional
project information is available on the homepage of the SMS Lab 2 .
In earlier projects at the SMS, isolated control of heart rate and diastolic
1
http://www.hocoma.com/en/products/erigo/
2
http://www.sms.mavt.ethz.ch/research/projects/awacon
2
blood pressure with the inclination angle as the only control input has
been done [4], [5]. In a next step, combined control of heart rate and dias-
tolic blood pressure has been succesfully tested with healthy subjects [6].
This latest version also contained another technical innovation: the idea was
to not only use as a control input, but also the stepping frequency fstep
which enables the controller to operate over an enlarged bandwith. For this
project, the described line of innovation is continued: the goal of this thesis
is to control heart rate, systolic and diastolic blood pressure with the two
control inputs and fstep . It is a fact, that the control strategy from the
isolated control problem, which consisted of an ordinary PI controller can not
be adopted for the new more complex control problem. The challenge is that
with an increasing number of inputs and outputs, there are more couplings
inside the system and PI control is not suitable anymore. For a multi-input
multi-output (MIMO) system, other control strategies have to be applied.
The first step consists of developing a cardiovascular model which is the topic
of chapter 3 which directly follows after the subsequent chapter about human
cardiovascular physiology (chapter 2). Chapter 4 continues with the control
design, followed by the results, the discussion and the conclusion (chapters 6,
7 and 8).
3
4
Chapter 2
Human cardiovascular system
This chapter will give a short introduction to physiology and pathophysio-

logy of the human cardiovascular system and summarises some results from
literature.
2.1 Hemodynamic system
Head
Right lung Left lung
Right Left heart

heart
Splanchnic &
renal circulation
Legs
Figure 2.1: Schematic representation of the human circulatory system. Adap-

ted from: http://www.ionwave.ca
The major task of the hemodynamic system is to supply every single cell
5
of the organsim with oxygen and nutrients and carry away carbon dioxide
(CO2 ) as well as metabolic waste products. In the circulation, the heart acts
as a pump which produces a pressure gradient between arterial and venous
circulation. Driven by this pressure gradient, deoxygenated blood from the
venous circulation flows back to the right heart where it is pumped through
the lung. In the lung the blood is enriched with oxygen and reenters systemic
circulation when pumped into the aorta by the left ventricle. The arterial
tree then supplies the whole body with oxygen and nutrients. From the
peripheral regions, where the oxygen and the nutrients are used, the blood
returns to the right heart and the circulation is closed (Figure 2.1).
Flows and pressures within the human hemodynamic system are characteri-
sed by the following list of hemodynamic variables:
Stroke volume (SV ) defines the amount of blood pumped into the aorta
within one beat.
Cardiac output (CO) is calculated as the product of stroke volume and

heart rate (HR)
CO = SV HR
Systolic blood pressure (sBP ) is the maximal blood pressure that oc-
curs during the contracting heart phase (systole).
Diastolic blood pressure (dBP ) is the minimal blood pressure that

occurs during the filling period of the heart, when the ventricles are
relaxed (diastole).
Mean arterial pressure (M AP ) is defined as the integrated blood pres-

sure over one heart period divided by the time of one heart period.
R t+tRR
t
BP (t)dt
M AP =
tRR
where BP (t) is the continuous blood pressure and tRR is the time of
one heart period (R-R interval). A common approximation is given as
1 2
M AP = sBP + dBP
3 3
Central venous pressure (CV P ) is the pressure in the intrathoracic

veins and the right atrium. Normal values range from 2 to 4 mmHG [7].
6
Total peripheral resistance (T P R) is a rather hypothetic measure of
vessel resistance in the systemic circulation. In duality to Ohms law
U = R I, total peripheral resistance is defined as
M AP CV P
TPR =
CO
M AP
CV P is usually neglected in this calculation and we get T P R = CO
.
2.2 Blood pressure regulation

Regulation mechanisms in the cardiovascular system are responsible for adap-
ting the hemodynamic variables such as blood pressure and cardiac output
according to the body needs. During exercise for example, cardiac output
is strongly increased in order to cover the high oxygen need in the skeletal
muscles. Another situation where these regulation mechanisms are active is
when the body adapts to changes in environmental conditions such as tem-
perature differences. And last, these mechanisms are also active in response
to orthostatic stress what will be of interest for blood pressure and heart rate
control on the ERIGO.
Hemodynamic variables can be influenced in several ways. Natural control
mechanisms include neurogenic (over the vegetative nervous sytem), hormo-
nal (over circulating hormones), humoral (with locally formed substances)
or myogenic regulation (vasoconstriction with smooth musculature). For
short-term regulation the neurogenic mechanisms which include baroreflex,
cardiopulmonary reflex and chemoreceptor reflex are most important. These
three types of neurogenic blood pressure regulation will now be described in
more detail:
The baroreflex plays a central role in short-term blood pressure regulation.
The baroreceptors which are located in the aortic arch and the carotid sinus
are the sensors in this reflex mechanism. They transmit neural signals to the
central nervous system or more precisely to the cardiovascular centre in the
medulla oblongata. The impulse frequency of the afferent neurons is determi-
ned by the course of the arterial blood pressure: Low arterial blood pressure
leads to a high impulse frequency. However, impulse frequency is not only
determined by absolute value of the arterial blood pressure but also by its
time rate of change. This proportional-derivative (PD) sensor characteristics
enable the baroreceptors to send all relevant information about heart func-
tion to the central nervous system. In the medulla oblongata the information
from the baroreceptors is transmitted to the efferent vegetative nervous sys-
tem which determines heart rate, heart contractility and vasoconstriction of
7
peripheral blood vessels, closing the reflex arch. It has to be added that an
inhibitory interneuron in the medulla provokes negative feedback which is
essential for regulating and stabilising arterial blood pressure.
Head
Baroreceptors Cardiovascular
centre
Right lung Left lung
Regulate heart rate & Baro-

cardiac contractility reflex
Right
heart Left heart
Splanchnic &
renal circulation
Regulate peripheral resistance
Legs
Figure 2.2: Blood pressure regulation with the baroreflex loop.
The cardiopulmonary reflex is another blood pressure regulating mechanism

that works synergistically with the baroreflex. The cardiopulmonary recep-
tors are located in the venous system, more precisely in the atria and A.
pulmonalis. However, cardiopulmonary receptors are not only responsible
for blood pressure regulation but also for volume regulation. Stimulation of
the receptors by dilated atria leads to an inhibited production of the anti-
diuretic hormone (ADH). As a consequence, urine secretion is increased and
the circulating blood volume can be reduced. Furthermore, activation of the
cardiopulmonary receptors decreases sympathetic activity and inhibits Renin
production in the kidneys. Renin promotes the formation of Angiotensin II
which has a direct vasoconstrictive effect on the smooth musculature in the
vessels. Moreover, Angiotensin II stimulates the production of Aldosterone
in the kidneys which increases reabsorption of sodium and water. In the long
term, this leads to a higher blood volume and an increased blood pressure.
Hence, the Renin-Angiotensin-Aldosterone system (RAAS) is capable of in-
creasing arterial blood pressure by the vasoconstrictive effect of Angiotensin
II and the volume retention caused by Aldosterone. Note that volume re-
gulation is a long-term regulation because it includes hormonal mechanisms
8
and because it takes some time until body fluids have diffused through the
capillary walls.
The chemoreceptor reflex is mainly responsible for respiration control, but
can also influence cardiovascular regulation if partial pressure of oxygen in
the blood decreases [7]. The reflex mechanism particularly becomes active
if blood pressure falls below 80 mmHg and once active, it acts in the same
feedback structure as the baroreflex. As a result, arterial blood pressure is
increased.
In detail, myogenic regulation is also a kind of neural regulation mechanism
if we consider the sympathetic effected vasoconstriction in the peripheral ar-
terioles. However, there is also a mechanism called autoregulation that is
attributed to myogenic regulation. Autoregulation is the ability of a blood
vessel to keep the blood flow constant under changing perfusion pressures.
When perfusion pressures are increased, the smooth musculature is activa-
ted and prohibits further expansion of the vessel walls (myogenic reaction:
Bayliss effect).
2.3 Orthostatic reaction and muscle pump

Everybody knows the dizzy feeling after standing up too fast in the morning.
The bodys internal regulation mechanisms are strongly challenged in such si-
tuations. Normally, the neural regulation mechanisms as discussed above are
able to maintain homeostasis quite fast. Nevertheless, there might be situa-
tions where the regulation is incapable of keeping arterial blood pressure and
cerebral perfusion at a safe level. Low blood volume or high temperatures
for example are conditions that increase the risk of defective homeostasis.
This can lead to a syncope which can be rather dangerous when the fainting
person falls down on the floor or hits a hard object.
One cause of such a syncope is the venous blood pooling in the legs. In a heal-
thy person, up to half a litre of blood is shifted from the upper body to the
lower extremities [7]. Arterial blood pressure falls immediately and the reflex
mechanisms are activated. However, peripheral vasoconstriction caused by
sympathetic regulation is usually too weak in order to lower venous blood
pooling effectively. Fortunately, there is another mechanism besides the neu-
ral regulation which is capable of stabilising the cardiovascular system. The
principle behind this mechansim is that the contraction of the skeletal leg
muscles efficiently compresses the venous compartments, decreases venous
pooling and increases venous return to the heart. Because the venous valves
are closed, backflow is not possible and the blood is forced to return back to
the heart (figure 2.3). This muscle pump is always active when the skeletal
9
leg musculature is active, for example during walking.
Figure 2.3: The muscle pump mechanism stabilises the cardiovascular system
by efficiently reducing venous blood pooling and increasing venous return by
repeated contractions of the skeletal leg musculature. Source: University of
Minnesota
2.4 Cardiovascular pathology

Cardiovascular instability and orthostatic hypotension are common deficits
in bed-ridden patients [1], [2]. In spinal cord injury (SCI) patients, for
example, one reason for these deficits are the disrupted efferent sympathetic
pathways regulating heart rate, heart contractility and peripheral vasocons-
triction. Therefore, neural regulation mechanisms can not work properly
and blood pressure often drops dramatically in reaction to orthostatic stress.
The disturbed balance between sympathicus and parasympathicus leads to
an exaggerated increase in heart rate as a compensatory reaction to the blood
pressure decrease. This happens because parasympathetic heart rate regu-
lation is still intact in SCI patients as efferent parasympathetic nerves are
connected to the Vagus nerve and not to the spine. Naturally, sympathetic
nervous system disfunction is not the only reason for orthostatic intolerance
in neurological patients. Claydon et al. [8] summarise these factors for SCI
patients as follows:
10
Sympathetic nervous system disfunction
Altered baroreceptor sensitivity
Lack of skeletal muscle pump
Cardiovascular deconditioning
Altered salt and water balance
Baroreceptor sensitivity which is typically reduced in SCI patients is in tight

connection with the sympathetic nervous system disfunction. As explained
above, baroreflex regulation is severly damaged because of an impaired sym-
pathetic nervous system.
The lack of the skeletal muscle pump together with immobilisation and pro-
longed bed-rest are the reason for cardiovascular deconditioning which in
turn negatively affects the overall recovery. Lastly, Claydon et al. report
evidence that SCI patients have a decreased plasma volume as a result of an
impaired salt and water balance. This leads to problems in volume regula-
tion, i.e. hypovolemia and low resting blood pressure with a predisposition
to orthostatic intolerance.
2.5 Literature review

2.5.1 Cardiovascular responses to passive tilting
Passive tilting leads to an immediate increase of blood volume in the leg
veins of about half a liter [7]. Venous return is decreased and because of the
Frank-Starling mechanism stroke volume and pulse pressure are diminished
as well. To counter the blood pressure drop, neural reflexes are instantly
activated and sympathetic action is increased. This has two consequences:
Firstly, heart rate rises by approximately 20 % [7] and secondly, diastolic
blood pressure rises because of increased peripheral resistance. In contrast,
systolic blood pressure is normally rather constant [7], [9].
The above description is considered the healthy cardiovascular response to
passive tilting according to standard physiological work of reference such
as [7]. Table 2.1 lists the outcome of several studies about cardiovascular
responses to passive tilting involving healthy subjects. Note that most of
these experimental results conform with the standard physiological res-
ponse.
As the aim of the thesis and the whole project is to enhance therapy of neu-
rological patients, a quick survey of typical pathophysiological cardiovascular
11
year HR sBP dBP MAP
Hainsworth and Al-Shamma [10] 1988
Mukai et al. [11] 1995
Tanaka et al. [12] 1996
Cooke et al. [13] 1999
Yokoi and Aoki [14] 1999
Petersen et al. [15] 2000
Tulppo et al. [16] 2000
Toska and Walloe [17] 2002 n/a n/a
Heldt et al. [18, 19] 2003/04
Colombo et al. [20] 2005 n/a
Masuki et al. [21, 22] 2007
Chi et al. [23] 2008
Ramirez et al. [24] 2008
Table 2.1: Literature summary. means no significant change, means

significant increase, means significant decrease. (Adapted and completed
with HR from [5])
responses will be done. Table 2.2 presents standard cardiovascular responses

of SCI patients. All of these studies conform with the normal pathological
reaction to orthostatic stress in SCI patients as described in section 2.4. In
addition, on the basis of the work of Houtman [25] and Legramante [26] it
can be stated that the higher the lesion the bigger are the implications on
the cardiovascular system and the cardiovascular regulation.
year aetiology HR sBP dBP MAP

Corbett et al. [27] 1971 Tetrapl.
Houtman et al. [25] 2000 Normal n/a n/a
Parapl. n/a n/a
Tetrapl. n/a n/a
Legramante et al. [26] 2001 Normal
Parapl.
Tetrapl.
Table 2.2: Literature summary. means no significant change, means

significant increase and means significant decrease
12
2.5.2 Cardiovascular modelling
Computational models of the human cardiovascular system have been deve-
loped for many different purposes. An elaborate cardiovascular model can
be used to identify aetiologies of cardiovascular diseases such as orthostatic
intolerance (OI). Heldt et al. [28] have presented a complex mathematical mo-
del which reproduces cardiovascular responses to orthostatic stress. In their
study the model was used to investigate the mechanisms that cause postspa-
ceflight OI. Leaning et al. [29] formulated a detailed model intended to study
and predict the overall effects of an injected drug. However, a cardiovascular
model can also be used to examine specific aspects of the cardiovascular sys-
tem such as blood-pressure fluctuations and heart-rate variability [30], [31].
Most of these models are aimed at explaining a certain cardiovascular phe-
nomenon and are usually rather complex with a high model order. They are
normally based on a large number of compartments representing the different
parts of the circulation (heart chambers, ventricles, venous and arterial seg-
ments). Each compartment or reservoir has a certain pressure Pj and volume
Vj
Vj Vj0
Pj = (2.1)
Cj
where Cj is the compliance and Vj0 the unstressed or zero-pressure volume.
Most models that describe the overall cardiovascular system incorporate some
elements of nervous system regulation. The baroreflex plays an essential role
because it governs the short-term dynamics of blood pressure and heart rate.
Long-term dynamics are most often less important than short-term effects
and can be neglected in the model description. Therefore, blood pressure
regulation mechanisms such as RAAS do not need to be modelled.
There are hardly any cardiovascular models in literature which incorporate
an orthostatic component and are kept simple. One exception is in the work
of Akkerman [32] who presented a mathematical beat-to-beat model designed
for tilt-table experiments. He analysed the dynamics of cardiovascular signals
after fast tilt-up and tilt-down. The model forms the basis of the whole
controller design and will be explained in detail in the following section.
13
14
Chapter 3
Cardiovascular model1
In order to control physiological quantities such as blood pressure and heart

rate, an appropriate model of the cardiovascular system is needed. This
model should have two inputs, namely the inclination angle of the ERIGO
device and the stepping frequency fstep . Based on these inputs the model
should output heart rate, systolic and diastolic blood pressure (Figure 3.1).
HR

u = y = PS
f step P
D
Cardiovascular model
Figure 3.1: Inputs and outputs of the cardiovascular model
In order to develop a mathematical model of the human cardiovascular sys-

tem for blood pressure regulation, the following two assumptions are made:
For the internal blood pressure regulation, only the baroreflex is taken
into account. Other mechanisms such as the cardiopulmonary reflex
and the RAAS system are not needed to explain the main blood pres-
sure characteristics in tilt-up and tilt-down because they govern the
long-term dynamics.
1
The material in this chapter is closely related to Akkermans work [32]
15
The blood volume is constant and fluid movements through the capil-
lary walls are not considered.
So the model only contains the most important elements that are needed to
simulate orthostatic reactions, namely a closed hemodynamic system, a kind
of internal blood pressure regulation system and the influence of gravity and
stepping (Figure 3.2). These parts will be explained in detail in the following
sections.
3.1 Hemodynamic system

The hemodynamic system as explained in section 2.1 can be modelled as a
connected system of pipes representing blood vessels. The heart acts as a
pump, maintains systemic blood pressure and transports oxygen-poor blood
to the lung. The microcirculation in the peripheral parts of the body is the
bottleneck in the pipe system and is therefore also called the peripheral re-
sistance. The fact that blood vessels are not stiff tubes but compliant vessels
is accounted for by introducing a venous and an arterial reservoir which is
common engineering practice. In fact, the flattening effect that arterial com-
pliance has on the systolic blood pressure peaks is called the Windkessel
effect which is in accordance with the above mentioned engineering principle
of introducing reservoirs for the modelling of compliant tubes.
In Akkermans model, only the lung, the arteries and the veins are modelled
as proper compartments as defined by Equation 2.1. The volumes of these
compartments are denoted by VP , VA and VV respectively. In addition, each
of these compartments is attributed a compliance (CP , CA and CV ) and a
zero-pressure volume (VP 0 , VA0 and VV 0 ). According to Equation 2.1 the
compartment pressures at heart beat k + 1 can then be expressed as:
VV (k) VV 0
PR (k + 1) = (3.1)
CV
VP (k) VP 0
PL (k + 1) = (3.2)
CP
VA (k) VA0
PD (k + 1) = (3.3)
CA
where PR (k) is the right atrial pressure, PL (k) the left atrial pressure and
PD (k) the diastolic blood pressure which directly depends on the arterial
blood volume.
The flow between these three reservoirs is characterised by the following set
of equations where VP P (k) describes the volume in the pulmonary pipeline
16
Head
Cardiovascular
Lung Baroreceptors centre
B
VP , CP
Windkessel
Right VA , C A
PR
heart
QR
I Baro-
PL , QL reflex
Left heart PS , PD
VV , PV , CV
Venous reservoir
QW R
Peripheral circulation
Figure 3.2: Simplified representation of the human cardiovascular system

used for model synthesis. Adapted from [32]
which is needed to model the delay between right and left atrium. P denotes
the number of right stroke volumes that are in the pulmonary pipeline.
VP (k) = VP (k 1) + QR (k P ) QL (k) (3.4)

VA (k) = VA (k 1) + QL (k) QW (k) (3.5)
VV (k) = VV (k 1) + QW (k) QR (k) (3.6)
VP P (k) = VP P (k 1) + QR (k) QR (k P ) (3.7)
Based on the Frank-Starling law and the restitution properties of ventricular

myocardium, the left and right stroke volumes QL (k) and QR (k) depend on
the preload and the length of the previous R-R interval I(k 1). Akkerman
17
adapted these findings from [33]:
QR (k) = R PR (k)I(k 1) (3.8)

QL (k) = L PL (k)I(k 1) (3.9)
where R and L are constant factors called Starling factors. The periphe-
ral flow QW (k) depends on the peripheral resistance R(k) and the pressure
difference between the arterial and the venous segment.

I(k)
QW (k) = CA (PS (k) PV (k)) 1 exp (3.10)
R(k)CA
where PV (k) denotes venous pressure evaluated just after systole when the
right stroke volume has been ejected into the pulmonary pipeline:
VV (k 1) VV 0 QR (k)
PV (k) = (3.11)
CV
The equations for pulse pressure PP (k) and systolic blood pressure PS (k)
complete the hemodynamic system:
QL (k)
PP (k) = (3.12)
CA
PS (k) = PD (k) + PP (k) (3.13)
All the introduced variables are beat-to-beat variables which means that they
are updated at each heart beat. It is not clear, however, at which instant
of the heart beat these variables are refreshed. The systolic blood pressure
PS (k) for example is updated during the systole when the continuous blood
pressure curve peaks at its maximum value. In contrast, the diastolic blood
pressure PD (k) is updated at the end of the diastole. Each hemodynamic
variable has its natural physiological sampling instant. Another example are
the right and the left stroke volumes QR (k) and QL (k). These variables are
updated at the beginning of the systole when the stroke volumes are ejected
into the pulmonary pipeline and the aorta respectively. Figure 3.3 graphically
summarises the sampling instants of the introduced hemodynamic variables.
3.2 Blood pressure regulation

Blood pressure regulation is performed by different body mechanisms. There
are short-term regulations (minutes, hours) and long-term regulations (days,
18
Figure 3.3: Hemodynamic timetable describing at which moment of the heart
beat each hemodynamic variable is evaluated. Source: Akkerman [32]
weeks 2 ) as mentioned above. For the purpose of blood pressure and heart
rate control, only the short-term regulations have to be considered. There-
fore, the modeling will focus on the baroreflex mechanism. Katona et al. [34]
have developed a baroreflex model which is composed of a sympathetic and
a parasympathetic branch (Figure 3.4) which is widely used in computatio-
nal modelling of the human cardiovascular system. Based on a hypothetic
barosignal which is a function of arterial blood pressure and pulse pressure,
the model outputs the heart period. The model is split in two parts because
sympathetic and parasympathetic dynamics are rather different. Parasym-
pathetic activity leads to a fast decrease of heart rate which can be shown by
electrical stimulation of the Vagus nerve. In contrast, the sympathetic contri-
bution on heart rate is slower. In Katonas model there is a fixed boundary
between sympathetic and parasympathetic regulation. Of course, in reality
there is a smooth transition between these two types of blood pressure regu-
lation. However, it is not needed to map this behaviour to the model and this
intuitive simplification is very well applicable. It is even the case, that for
applications where these subtle dynamics are of minor importance, Katonas
baroreflex model can be further simplified. In this thesis, the two branches
are merged to one neglecting the different dynamics of sympathetic and pa-
rasympathetic regulation. More important is the extension of the model by
2
Time specifications: http://homepages.uel.ac.uk/M.S.Meah/bs250page4clec3.
htm
19
Figure 3.4: Katonas baroreflex model for heart rate regulation [34]. The
neural input signal f (t) is divided in a sympathetic (bottom) and parasym-
pathetic part (top) where defines the borderline between sympathetic and
parasympathetic regulation.
a branch for regulation of the peripheral resistance as proposed by Akker-

man [32]. This regulation is based on the sympathetic part of the hypothetic
neural barosignal and the implementation is straightforward (Figure 3.5).
Put in equations, the baroreflex model can be stated as follows:
scaling
B
PT1 + I

Bc +
out scaling
BS
PT1 -
in
+ R
Bc Bc +
RP +
Figure 3.5: Simplified baroreflex model (based on Katona [34] and Akker-
man [32]): the two branches regulating heart rate have been merged to one,
a second branch has been added for regulation of peripheral resistance.
20
B(k) = PB (k) + kP PP (k) kB (3.14)
1 2
= PS (k) + PD (k) B sin (k) + kP PP (k) kB (3.15)
3 3
BS (k) = min(B(k), Bc ) (3.16)
1 1

JBI (k) = e BI JBI (k 1) + 1 e BI B(k) (3.17)
1 1

JBR (k) = e BR
JBR (k 1) + 1 e BR
BS (k) (3.18)
I(k) = (JBI (k) + Bc ) (3.19)
R(k) = (Bc JBR (k)) + RP (3.20)
Please note, that this baroreflex model is a simplification of Akkermans
model. Please refer to Akkerman [32] for the original work.
3.3 Influence of gravity

The modelling of the orthostatic component describes how the angle of the
tilt-table influences the cardiovascular system and the physiological variables.
We are only interested in the gravity component Fg along the body axis which
is
Fg = g sin . (3.21)
Based on that, the first model input u1 (k) can be stated as follows:
u1 (k) = sin (3.22)
Gravity acts on every single blood vessel in the cardiovascular system and
creates rather large hydrostatic pressure differences in a standing human.
Arterial pressure is decreased by 25 mmHG at head level and increased by
95 mmHG at leg level [7]. The question arises how gravitational forces can be
integrated into the existing hemodynamic model. It is chosen to let gravity
directly affect the right and left atrial pressures PR (k) and PL (k) which is
a mathematically convenient alternative to modelling the whole hydrostatic
column [32]. The atrial pressures then depend on the gravity factors R (k)
and L (k):
(VV (k 1) VV 0 )R (k)
PR (k) = (3.23)
CV
(VP (k 1) VP 0 )L (k)
PL (k) = (3.24)
CP
R (k) = 1 R sin (k) (3.25)
L (k) = 1 + L sin (k) (3.26)
21
Besides the atrial pressures, also the mean arterial pressure at the level of
the baroreceptors PB (k) has to be corrected for the gravity influence. The
reason is the height difference between the baroreceptors and the heart, where
arterial pressure is evaluated.
1 2
PB (k) = PS (k) + PD (k) B sin (k) (3.27)
3 3
3.4 Influence of stepping

Akkermans model does not contain a component which describes the effects
of the muscle pump when the stepping mechanism is activated. Therefore,
these effects were analysed and subsequently added to the model.
The stepping mechanism acts on the cardiovascular system by activating the

muscle pump through continuous leg movements. This has the following
three immediate effects:
Compression of the venous leg compartments leads to an increase of

peripheral resistance.
The contracting skeletal muscles decrease expandability of the venous

vessels and hence, venous compliance is decreased.
The muscle pump alters the functionality of the baroreflex mechanism.

Similar to the situation of exercise, a resetting takes place and the
hypothetic pressure level at which neural regulation is switched from
parasympathetic to sympathetic action is increased.
Although the stepping mechanism moves the legs passively and we can only
speak of a passive muscle pump, the stabilising effects on the cardiovascular
system are still present, although diminished. Czell et al. [35] have conclu-
ded after their pilot study with healthy adults, that passive leg movements
stabilises blood circulation and prevents from syncopes. So fortunately, the
stabilising effects on the cardiovascular system are still there and can be ex-
ploited in the early rehabilitation process of neurological patients.
The above listed effects are transformed to mathematical equations so that
they can take influence on the existing cardiovascular model of Akkerman.
As stepping is the second input after the inclination angle, u2 (k) will be the
expression for the normalised stepping frequency:
fstep (k)
u2 (k) = (3.28)
fstep,max
22
where fstep,max is normally 48 steps
min
. As it takes some time for the cardiovas-
cular system to adapt to the stepping movements, u2 (k) has to be modelled
as a first-order system with the time constant step which is usually chosen
around 40 beats. In addition, the stepping influence at supine position has
experimentally been found to be very low (figure 3.11, first 10 minutes).
Thus, it is easiest to make u2 (k) linearly dependent on u1 (k). The adapted
stepping input is denoted as (k):
1 1
(k + 1) = e step (k) + 1 e step u2 (k)u1 (k) (3.29)
(k) now operates in an additive nature on peripheral resistance, venous

compliance and the neural barosignal:
R(k) = (Bc BS (k)) + RP + kSR (k) (3.30)

CV (k) = CV + kSC (k) (3.31)
B(k) = PB (k) + kP PP (k) kB kSB (k)
1 2
= PS (k) + PD (k) B sin (k) + kP PP (k) kB kSB (k)
3 3
(3.32)
23
3.5 Model simulations
The cardiovascular model can now be used to simulate and analyse heart rate
and blood pressure in response to various inputs. In addition, it is possible
to investigate other cardiovascular signals such as stroke volume, peripheral
resistance or cardiac output. In order to get an idea for what happens in the
body during a tilt manoeuvre, a standard fast tilt-up and tilt-down should
be examined first. Simulations have been done with standard steady-state
values as given in table 3.1. These values were used in combination with a set
of fixed parameters (table A.2) for identification of the unknown parameters
(appendix A.5).
Table 3.1: Standard steady-state values used for the model simulations:
stands for supine position ( = 0 , fstep = 0); + stands for tilted position
( = 76 , fstep = 0); s stands for stepping ( = 76 , fstep = fstep,max )
Steady-state value

HR 65
HR+ 80
PS 120
PS+ 125
PD 80
PD+ 95
HRs 75
PSs 130
PDs 95
3.5.1 Fast tilt-up and tilt-down

The adjective fast refers to the fact that the tilt-table angle changes from
the minimal angle of zero degrees to the maximal angle of 76 degrees in two
or three heart beats (vice versa for tilt-down). Of course, this is not feasible
in reality where a full tilt may take up to 30 seconds. However, it is a good
way to analyse the dynamics of such a fast tilt, which probably would not
be that pronounced when tilting at a slower rate.
Fast tilt-up
Model responses with the most important physiological variables are depicted
in Figure 3.6. It can be seen that these responses are in accordance with the
standard physiological response of tilt-up. Details about the dynamic cha-
24
racteristics will be explained in the following paragraph about fast tilt-down
simulation. The reason is that tilt-down responses are usually much faster
than tilt-up responses and that the dynamic features are easier to identify
and explain.
Fast tilt-down
When a person is tilted from the initial upright position back to the supine
position, blood is shifted in the body under the influence of gravity. This has
two immediate effects:
Blood in the pulmonal pathways is shifted into the lung reservoir cau-
sing a lack of blood in the left atrium.
Blood from the venous reservoir is forced back to the right atrium and
venous return is increasing rapidly.
The first effect leads to a fast decrease in arterial blood pressure and left
stroke volume. As the blood supply in the left atrium is abruptly dimi-
nished, the left stroke volume is immediately decreased according to the
Frank-Starling law. This process is visible in the simulated model responses
as the initial negative peak in blood pressure, left stroke volume and left
atrial pressure.
The second effect causes an immediate rise of right stroke volume in response
to the increased venous return. After some time, this extra blood volume
has made its way through the pulmonal pathways and ends up in the left
atrium. This in turn causes the left stroke volume to rise again and leads
to the positive blood pressure peak 7 to 8 seconds after the start of the tilt
manoeuvre.
In a third phase the phyisological signals settle to their steady-state values
which is the case after approximately 20 seconds. Left and right stroke
volume are balanced and the above description nicely shows how the Frank-
Starling mechanism enables the adjustment of left and right stroke volume
according to respective ventricle load.
3.5.2 Stepping
As the stepping influence on the cardiovascular system is biggest when the
table is fully tilted, only the simulation results for = 76 are shown (Fi-
gure 3.8). The heart rate shows the expected non-minimum phase behaviour
as described by [6], the diastolic blood pressure is hardly influenced and the
25
systolic blood pressure rises, as described by [5]. The barosignal shows the in-
verse behaviour of the heart rate, which makes perfect sense as the barosignal
directly determines heart rate. Peripheral resistance is decreased when step-
ping is activated which can be compared to the adaptation of the peripheral
resistance to exercise. The increase of the stroke volumes and the pulse pres-
sure point out the stabilising effect of stepping on the cardiovascular system.
3.5.3 Quasi-static
The reason for a quasi-static simulation of the cardiovascular model is the
analysis of the steady-state behaviour of heart rate and blood pressure at
all angles in the admitted range. Only the angle input is considered for
this simulation because the stepping acts smoothly on the outputs whereas
the system is expected to show rather different behaviour in the sympathetic
and the parasympathetic region respectively. Remember that although the
baroreflex regulation on heart rate is active over the whole range, periphe-
ral resistance is only influenced by sympathetic regulation (see section 3.2).
Figure 3.9 depicts the dependencies of the relevant cardiovascular variables
on the inclination angle . The following observations can be made:
Heart rate strictly increases with and shows an S shape:
The heart rate characteristics directly follow from the baroreceptor
signal which is based on the arterial pressure at the level of the baro-
receptors.
Systolic blood pressure both increases and decreases at lower angles,
and strictly increases at higher angles:
Systolic blood pressure PS is calculated as the sum of diastolic blood
pressure PD and pulse pressure PP . At small angles, stroke volumes
dont change much, but PD is increased. This leads to the increase
in PS at small angles. However, as soon as the stroke volumes and
subsequently the pulse pressure is decreased, PS is decreased as well.
In the sympathetic regulation domain, PS strictly increases because PD
grows faster than PP declines.
Diastolic blood pressure strictly increases with , but at a lower rate
at lower angles:
The reason is that at higher angles peripheral resistance is increased
by the baroreflex which leads to higher arterial pressures.
Peripheral resistance by design only increases at higher angles, when
sympathetic regulation becomes active.
26
Stroke volumes are diminished when tilting.
Figure 3.10 compares the results from the quasi-static simulation with results
from Hainsworth [10], Matalon [36], Heldt [28], Fisler [37] and Nguyen [5].
It can be deduced that the accordance of the model results with literature
studies and previous work at SMS is satisfying.
27
90
80
Heart rate
60 80
Angle
[bpm]
[deg]
40
70
20
0 60
0 50 100 0 50 100
Heart beats Heart beats
140 90
Blood pressure
120
Barosignal 80
[mmHG]
P
S
[mmHG]
P 70
100 D
60
80
50
0 50 100 0 50 100
5
Stroke volumes
Atrial pressures
P 80 QL
L
[mmHG]
4
[ml]
60
P
3 R QR
40
2
0 50 100 0 50 100
Peripheral resistance
5.5
1600
[mmHG ms/ml]
Cardiac output
5
[l/min]
1400
4.5
1200 4
1000 3.5
0 50 100 0 50 100
Figure 3.6: Simulation of a fast tilt-up without stepping
28
90
80
Heart rate
60 80
Angle
[bpm]
[deg]
40
70
20
0 60
0 50 100 0 50 100
140 90
Blood pressure
80
Barosignal
120
[mmHG]
[mmHG]
P
S
70
100
P
D 60
80
50
0 50 100 0 50 100
5
Stroke volumes
Atrial pressures
P 80 Q
L R
[mmHG]
4
[ml]
60
QL
3 P
R
40
2
0 50 100 0 50 100
5.5
1600
[mmHG ms/ml]
Cardiac output
5
[l/min]
1400
4.5
1200 4
1000 3.5
0 50 100 0 50 100
Figure 3.7: Simulation of a fast tilt-down without stepping
29
82
80
[steps/min]
40
Heart rate
Stepping
[bpm]
78
20
76
0 74
0 50 100 150 0 50 100 150
Systolic blood pressure
132 65
130 Barosignal
[mmHG]
[mmHG] 60
128
55
126
124 50
0 50 100 150 0 50 100 150
Diastolic blood pressure
100 65
Stroke volumes
[mmHG]
60
[ml]
95
55
90 50
0 50 100 150 0 50 100 150
1550 4.6
[mmHG ms/ml]
Cardiac output
1500 4.4
[l/min]
1450 4.2
1400 4
0 50 100 150 0 50 100 150
Figure 3.8: Simulation of an activation of the stepping mechanism ( = 76 )
30
80 80
Heart rate
60 75
Angle
[bpm]
[deg]
40
70
20
65
0
0 500 1000 1500 0 500 1000 1500
Systolic blood pressure
100
126
Barosignal
[mmHG]
[mmHG]
124 80
122
60
120
118 40
0 500 1000 1500 0 500 1000 1500
Diastolic blood pressure
100 80
Stroke volumes
[mmHG]
90 70
[ml]
80 60
70 50
0 500 1000 1500 0 500 1000 1500
4.8
1500
[mmHG ms/ml]
Cardiac output
4.6
[l/min]
1400
4.4
1300 4.2
1200 4
0 500 1000 1500 0 500 1000 1500
Figure 3.9: Quasi static simulation without stepping
31
20 20
Hainsworth Hainsworth
Matalon Smith
18 18
Fisler Model
Model
16 16
14 14
12 12
dBP [mmHG]
HR [bpm]
10 10
8 8
6 6
4 4
2 2
0 0
2 2
0 20 40 60 80 0 20 40 60 80
Angle [deg] Angle [deg]
Figure 3.10: Comparison of steady-state behaviour. Left: HR as a function

of . Right: Diastolic BP as a function of
32
3.6 Model validation
The step of model validation will be performed using measurements from
three healthy subjects (see chapter 5.1.3). Evaluation will be done in a
qualitative way analysing each measurement separately. Although averaging
over all subjects would probably yield better agreement between the model
simulation and the measurement, interesting details from the individual cases
would be lost.
The measurement was divided into an identification and a validation part.
The according measurement protocol is illustrated in the lowermost plot of
figure 3.11. Note that between the identification and the validation there was
a recalibration of the blood pressure measurement device. This can introduce
offsets in some cases whereas diastolic blood pressure seems to be affected
the most. In figure 3.11 for example, this offset amounted to about 4 mmHg
and has been corrected accordingly.
Validation results for the first subject (MW) are satisfying and it demons-
trates that it is possible to simulate or predict heart rate and blood pressure
dynamics.
HR [bpm]
80
60
0 10 20 30 40 50 60 70
Time [min]
120
sBP [mmHG]
100
80
0 10 20 30 40 50 60 70
Time [min]
dBP [mmHG]
80
60
40
0 10 20 30 40 50 60 70
Time [min]
fstep [steps/min]
fstep
[deg] /
50
0
0 10 20 30 40 50 60 70
Time [min]
Figure 3.11: Model validation with subject MW
33
However, the identified models for the other two subjects deviate more from
the measured signal than it was the case for the first subject. This should be
analysed in more detail: For the second subject (figure 3.12) it can be said
that heart rate and diastolic blood pressure were well reproduced by the mo-
del. Systolic blood pressure, however, did not show clear trends: During the
identification phase, systolic blood pressure stayed constant when tilting but
increased in the end of the experiment during the slow ramp of the inclina-
tion angle. Another issue are the calibration offsets, that have already been
mentioned above. For the second subject, diastolic blood pressure jumped
by about 10 mmHg which has been corrected for in the modelled diastolic
blood pressure curve. Already the low values of about 40 mmHg after 17
minutes are unrealistic compared to the baseline values at the beginning of
the experiment which were around 55 mmHg. The worse thing however is
that after the recalibration the value is not set back to 55 mmHg but is even
increased to about 65 mmHg. These huge jumps in the measured signals
are physiologically improbable in such a short timespan and it unveils the
weaknesses of the blood pressure measurement device.
90
HR [bpm]
80
70
60
50
0 10 20 30 40 50 60 70
Time [min]
120
sBP [mmHG]
100
80
0 10 20 30 40 50 60 70
Time [min]
dBP [mmHG]
80
60
40
0 10 20 30 40 50 60 70
Time [min]
fstep [steps/min]
fstep
[deg] /
50
0
0 10 20 30 40 50 60 70
Time [min]
Figure 3.12: Model validation with subject MSW
34
The validation measurement for the third subject emphasises the above men-
tioned problems: First, systolic blood pressure is hard to reproduce or model.
Second, diastolic blood pressure measurement is tampered with calibration
offsets. However, it has to be added that the last measurement is an extreme
example for what can happen with physiological signals.
100
HR [bpm]
80
60
0 10 20 30 40 50 60 70
Time [min]
180
sBP [mmHG]
160
140
120
100
80
0 10 20 30 40 50 60 70
Time [min]
dBP [mmHG]
80
60
0 10 20 30 40 50 60 70
Time [min]
fstep [steps/min]
fstep
[deg] /
50
0
0 10 20 30 40 50 60 70
Time [min]
Figure 3.13: Model validation with subject DH
Generally, it can be concluded that the model reproduces heart rate and
diastolic blood pressure with a satisfying accuracy. Problems occur, if repro-
ducibility is not given, i.e. if the subject responds differently for the same
inputs. However, this is a more general issue as any deterministic model
would struggle with low reproducibility.
In contrast to heart rate and diastolic blood pressure, systolic blood pressure
is more difficult to predict and model for healthy subjects. Still, we decided
to go on with the strategy of controlling all three variables, because in the
end, the system will be used with patients. Patients usually react much bet-
ter with systolic blood pressure to verticalisation because neural regulation
is impaired.
To counter the problem with calibration offsets, it will be important not to
35
do a calibration between identification and control or to reidentify the model
when a calibration is necessary. If the offset is only small, it may not be nee-
ded to reidentify the model because for control only the relative responses
are important. However, if the offset is too high and the new values are
out of the identified range, it gets impossible to start the control experiment
without adapting the model.
36
Chapter 4
Control design
Starting from the non-linear MIMO system derived in the previous chapter,
an appropriate controller will now be developed. This controller has to be
able to keep heart rate and blood pressure within reasonable bounds and
minimise fluctuations by adjusting the inclination angle and the stepping
frequency. For the given MIMO system which is apparently strongly coupled,
a SISO approach trying to control each output in an isolated manner seems
infeasible. The fact that the system has less inputs than outputs makes it
even harder to do so. It is therefore advisable to choose a control strategy
which can handle these issues. A linear optimal control approach is frequently
used in advanced control applications, and has been chosen for this thesis as
well. Two controllers have been developed, implemented and tested: a Linear
Quadratic Regulator (LQR) and a Model Predictive Controller (MPC).
The LQ controller which was augmented by an integral part in order to
eliminate steady-state control errors was experimentally found to be very
hard to tune. The reason is that the system is likely to operate near or on the
constraints boundaries for the control inputs. As a result, control inputs are
often saturated and anti-windup strategies are therefore necessary. However,
for a true MIMO system with strong couplings as has been developed in the
previous chapter it is difficult to apply standard anti-windup techniques. It is
therefore desirable to have a technique which intrinsically accounts for input
constraints. This explains why Model Predictive Control (MPC) is suited for
the application at hand and why it is to prefer to a common LQ regulator.
4.1 Model predictive control (MPC) design

The advantages of Model Predictive Control are manifold. Two of the most
important features are that MPC takes account of actuator limitations and
37
that it is suited for multivariable control problems. The principle behind
MPC is as follows: based on the system model the controller predicts future
outputs and finds the optimal control inputs by minimising a certain cost
function. An intuitive analogon for MPC is driving a car [38]. Imagine
that the reference path is the lane, the plant is the car and the controller is
represented by the driver. The control objective is to keep the car on the
lane, while steering as little as possible, keeping a certain distance to the
kurbs, obey speed limitations and so on. The driver now has an internal
belief or model of how the car reacts to his inputs. He uses this knowledge
to predict future behaviour of the car and give according control inputs in
order to stay on the reference path, minimise steering effort and meeting all
given constraints.
This control problem can generally be formulated with a cost function and
according constraints [39].
min J = (rs yp )T Q(rs yp ) + uT Ru (4.1)

u
Mu (4.2)
where u(mNc 1) is the control input, yp (pNp 1) the predicted output,

rs (pNp 1) the reference, Q(pNp pNp ) the output weighting matrix and
R(mNc mNc ) the control input weighting matrix. The matrix M(4mNc
mNc ) and the vector (4mNc 1) define the constraints. The scalars n,
m and p are the number of states, the number of inputs and the number of
outputs of the MIMO system. The control horizon is denoted as Nc . Table 4.1
summarises these notations. As we will only need constraints on the control
inputs, state and output constraints are neglected in this formulation. Note
that the vectors rs and yp contain Np discrete samples over the prediction
horizon and the vector u contains Nc discrete samples over the control
horizon:
T
u = u(k) u(k + 1) u(k + 2) u(k + Nc 1) (4.3)
T
yp = yp (k + 1) yp (k + 2) yp (k + 3) yp (k + Np ) (4.4)
T
rs = rs (k + 1) rs (k + 2) rs (k + 3) rs (k + Np ) (4.5)
Based on the above given description, a model predictive controller will now
be developed for the given nonlinear cardiovascular model of chapter 3. Fi-
gure 4.1 sketches the signal flows of the control system and shows the two
major parts of the controller which are the optimisation routine and the state
observer.
38
Table 4.1: MPC glossary.
Variable Value Description

Np 5 Prediction horizon
Nc 2 Control horizon
Tu 20 s Controller sample time
Nu - Number of heart beats in Tu
n 10 Number of states
m 2 Number of inputs
p 3 Number of outputs
r - Reference signal
Q Eq. 4.20 Weighting matrix for states
R Eq. 4.21 Weighting matrix for control actions
x, y, u - Non-linear state, output, input
xlin , ylin , ulin - State, output, input of linearised model
x
, y, u - State, output, input of augmented linearised model
State observer
The state observer is needed because with the exception of the heart inter-
val the system states are not measurable. The states are updated in each
time step with the non-linear cardiovascular model equations and are then
corrected in a second step based on the error between the observed and mea-
sured outputs. Basically, this is nothing else than a traditional Kalman filter
doing first a prediction update followed by a measurement update. The only
difference is that the states are updated in a non-linear way. Algorithm 1
describes the state observer in pseudo code.
Algorithm 1 State observer

1: if x
is not defined (start of control experiment) then
2: x
= baseline values
3: end if
4: Save previous state estimate x old = x
5: Nonlinear prediction update: [ y x ] = f (
x, u)
6: Measurement update: x =x + Kob (y y)
7: Output x=x x old
The baseline values x

describe the system state at the supine position without
stepping (u = (0 0)T ). x is calculated during parameter identification as
a byproduct (appendix A.5). f ( x, u) denotes the non-linear cardiovascular
39
model (appendix A.3).
The observer gain Kob is calculated in a stochastically optimal way based on
the linearisation about the current set-point where w(k) is the process noise
and v(k) the measurement noise (eq. 4.6).
xlin (k + 1) = Alin xlin (k) + Blin (ulin (k) + w(k)) (4.6)

ylin (k) = Clin xlin (k) + v(k)
Values for the entries of the diagonal covariance matrices W = E(wwT )

and V = E(vv T ) are given in Table 4.2. Measurement noise was calculated
based on the assumption that each output (HR, PS , PD ) has a standard
deviation of 2 bpm or 2 mmHg respectively. Process noise was set based
on experimental findings, such that the estimated outputs converged to the
measured outputs and noise rejection was satisfying. Note that the high value
of V(1, 1) is explained by the fact that the first component of ylin is the R-R
interval which has much higher nominal values than the other components
of ylin .
Table 4.2: Entries of covariance matrices W and V
Entry Value
V(1, 1) 0.03252
V(2, 2) 0.01672
V(3, 3) 0.02502
W(1, 1) 0.042
W(2, 2) 0.042
Minimise cost
rS function
u y
+ - x
Observer
MPC Cardiovascular model
Figure 4.1: MPC overview
40
Optimisation routine
The prediction or the optimisation is based on system 4.6 without noise:
xlin (k + 1) = Alin xlin (k) + Blin ulin (k) (4.7)

ylin (k) = Clin xlin (k)
However, instead of equations 4.7 an augmented state-space model, contai-

ning an additional integrator, will be used for the prediction (equations 4.8).
This has the advantage that the current control error ylin (k) is included in
the description which penalises deviations from the set-point.
Augmented state-space model:

xlin (k + 1) Alin 0nm xlin (k) Blin
= +
u(k)
ylin (k + 1) Clin Alin Ip ylin (k) Clin Blin
| {z } | {z }
=:A =:B
(4.8)

xlin (k)
y(k) = 0pn Ip
| {z } ylin (k)
=:C | {z }
=:
x(k)
where I denotes the identity matrix and 0 the null matrix. We will now derive
the elements of equation 4.1 based on Wang [39]: The state x (k) develops
according to the augmented state-space model. Note that u(k) = u(k).
x
(k + 1) = Ax(k) + Bu(k) (4.9)
x
(k + 2) = Ax(k + 1) + Bu(k + 1) (4.10)
= A2 x
(k) + ABu(k) + Bu(k) (4.11)
..
.
(k) + ANp 1 Bu(k) + ANp 2 Bu(k + 1) + . . . (4.12)
(k + Np ) = ANp x
x
+ ANp Nc Bu(k) (4.13)
The output at time instant k + i then is:
y(k + i) = CAi x
(k) + CAi1 Bu(k) + CAi2 Bu(k + 1) + . . . (4.14)
+ CAiNc Bu(k), i = 1, . . . , Np
The predicted output y(pNp 1) can be written in vector form using F(pNp
41
n) and (pNp mNc ):

y(k + 1)
y(k + 2)
y = = F
x(k) + u (4.15)

..
.
y(k + Np )
where
CA
CA2
F = .. (4.16)

.
CANp

CB 0 0 0 0

CAB CB 0 0
0
=
CA2 B CAB CB 0
0
.. .. .. .. ... ..
. . . . .
CANp 1 B CANp 2 B CANp 3 B CANp 4 B CA Np Nc
B
(4.17)
The cost function at time instant k can now be written as follows:
J(k) = yT Q
y + uT Ru (4.18)
T T
= (F
x(k) + u) Q(F
x(k) + u) + u Ru (4.19)
The weighting matrices Q(pNp pNp ) and R(mNc mNc ) are defined based
on the maximal input and output values (umax , ymax ):

q1 0 0 0 0 0
.. . . . . .. ..
. . .. .. . .

0 0 qp 0 0 0

0 0 0 q1 0 0

Q=
. (4.20)
.. .. .. .. . . .
. . . . ..
0 0 0 0 0 q
p
.. .. .. .. .. .. ..
. . . . . . .
42

r1 0 0 0 0 0
.. . . . .. .. ..
. . .. . . .

0 0 rm 0 0 0

0 0 0 r1 0 0

R=
. (4.21)
.. .. .. .. . . .
. . . . ..
0 0 0 0 0 r
m
.. .. .. .. .. .. ..
. . . . . . .
where
1
qi = 2
i = 1, . . . , p (4.22)
yi,max
1
rj = j = 1, . . . , m (4.23)
u2j,max
The above mentioned cost function (eq. 4.18) has to be minimised under
some constraints on u(k) and u
(k).
umin <= u(k) <= umax (4.24)

umin <= u
(k) <= u
max (4.25)
These constraints can also be written in matrix form as a function of the

optimisation vector u:

M1 N1
u (4.26)
M2 N2
where M1 (2mNc mNc ) and N1 (mNc 1) define the constraints on the

amplitude of the control signal:
Im 0m 0m 0m

Im Im 0m 0m
.. .. .. .. ..

. .

. . .
m m m m m
I I I I I
M1 = m (4.27)

I 0m 0m 0m

m
I Im 0m 0m

. .. .. .. ..
.. . . . .
Im Im Im Im Im
43
max u (k 1)

u
max u
u (k 1)

..
.

N1 = (4.28)

umin + u (k 1)

umin + u (k 1)

..
.
M2 (2mNc mNc ) and N2 (2mNc 1) define the constraints on the difference
of the control signal and can be written down similarly:
mN
I c
M2 = (4.29)
ImNc

umax
umax
..
.

N2 = (4.30)

umin

umin

..
.
Finally the objective is to minimise the cost function J(k) subject to the
given constraints:
min J(k) = (F x(k) + u) + uT Ru
x(k) + u)T Q(F (4.31)
u

M1 N1
u
M2 N2
In order to incorporate anticipative action or look-ahead functionality in
the MPC design, the objective can be reformulated:
min J(k) = (rs (F x(k) + u + ys )) + uT Ru
x(k) + u + ys ))T Q(rs (F
u
(4.32)

M1 N1
u
M2 N2
where ys (pNp 1) denotes the non-linear output at the setpoint:

ys (k)
ys (k)
ys = .. (4.33)

.
ys (k)
44
Note that the reference rs is also given with real physiological values for the
R-R interval, systolic and diastolic blood pressure.
The minimisation can be done by standard quadratic programming routines.

Note that such routines generally assume the quadratic programming pro-
blem in the form of equation 4.34. It is left to the reader to verify that
equation 4.32 can be reformulated to equation 4.35 in order to meet this
requirement.
1
min J = uHu + f T u (4.34)
u 2
Mu
1
min J(k) = u(T Q + R)u + (T Qrs + T QF
x(k) + T Qys )u
u 2
(4.35)

M1 N1
u
M2 N2
Adaptations for controller sample time
If the calculated control action is not sent to the plant in every time step, but
only every Nu time steps, the optimisation problem has to be reformulated.
This is the case for our plant, where the subject on the ERIGO would feel
uncomfortable if control commands were sent in every heart beat. Further,
two much motion of both the tilt-table and the stepping mechanism would
needlessly activate the cardiovascular system. It is therefore necessary to
choose a controller sample time Tu which is higher than the time needed for
one time step of the augmented system 4.8 (i.e. one heart beat). Note, that
this change does not influence the observer, which still runs at the original
sample time.
The optimisation vector u now has the form

u(k)
u(k + Nu )

u = (4.36)

..
.
u(k + Np Nu )
45
The objective is the same as before (equation 4.32), but the prediction ma-
trices and the reference vector rs change:

CANu
CA2Nu
F= (4.37)

..
.
CANp Nu
PNc Nu i

i=1 CA B 0 0
Nc CA2Nu i B
P PNc Nu i

i=1 CA B 0
Pi=1
Nc CA3Nu i B P Nc 2Nu i

= i=1 i=1 CA B 0

.
.. .
.. .. ..
. .
PNc NP Nu i Nc (NP 1)Nu i
PNc
CA(NP Nc +1)Nu i B
P
i=1 CA B i=1 CA B i=1
(4.38)

rs (k)
rs (k + Nu )
rs = (4.39)

..
.
rs (k + Np Nu )
Note that Nu is calculated at the beginning of the MPC calculation every Tu
seconds based on the current heart rate, i.e. the current R-R interval y1 in
milliseconds:
1000 Tu
Nu = (4.40)
y1
4.2 Simulation
In order to test the controller behaviour a simple test case has been set up.
The cardiovascular model has been identified with the standard steady-state
values from table 3.1. Two setpoints around = 60 and = 30 with
deactived stepping have then been calculated. Linearisations and Kalman
observers were obtained around these setpoints and have then been used for
the controller.
Now, the first part of the simulation consists of a reference step from the
first setpoint ( = 60 ) to the second setpoint ( = 30 ). The controller
anticipates the step as soon as it is included in the prediction horizon which
is 100 s (Np = 5, Controller sample time = 20 s). It can be seen that not only
the angle is lowered, but also the stepping mechanism is activated because it
quickly decreases heart rate.
46
The second part of the simulation depicts the reaction of the controller to a
disturbance on the outputs: heart rate is suddenly increased by four beats
per minute, and systolic blood pressure is decreased by four mmHg. The
controller reacts by activating the stepping mechanism which is capable to
compensate such a disturbance. As a consequence, the outputs are regulated
back to the reference values.
80
[bpm]
HR
75
0 1 2 3 4 5 6 7 8
Time [min]
125
Systolic BP
[mmHG]
120
115
0 1 2 3 4 5 6 7 8
Time [min]
95
Diastolic BP
[mmHG]
90
85
80
0 1 2 3 4 5 6 7 8
Time [min]
fstep [steps/min]
f
[deg] /
50 step
0
0 1 2 3 4 5 6 7 8
Time [min]
Figure 4.2: Controller simulation: The first part depicts the system response
to a step at minute 2. The second part shows the system response to a
disturbance in heart rate and systolic blood pressure at minute 5.
47
48
Chapter 5
Methods
5.1 Healthy subjects

5.1.1 Implementation
The healthy subjects were measured at the SMS lab, where the ERIGO device
has been customised for easy interfacing and data recording. No changes had
to be done on the hardware side. As for the software, the controller could be
implemented into an existing Matlab/Simulink environment that interfaces
with the ERIGO via an xPC target machine. From Matlab, the model is
transformed to C code, compiled and loaded on to the target machine. This
requires all code in the model to be written in EML-code, which is basically
Matlab m-code with some restrictions. The restrictions are such, that only C
compatible code is allowed, which means that variable sizes need to be clearly
defined in advance for example. Furthermore, not all Matlab functions are
available including the quadratic programming solver quadprog and all
control system related functions such as ss or kalman that are needed
for control design. The model predictive controller, which needs a quadratic
programming solver in order to do the optimisation, has thus been realised
with the open-source C++ implementation qpOASES 1 which is based on
the active-set strategy [40]. Control design has been done offline.
5.1.2 Blood pressure recording

Continuous blood pressure recording was done with the non-invasive CNAPTM Monitor
500 2 (Figure 5.1). The CNAPTM Monitor outputs the raw blood pressure
1
http://www.kuleuven.be/optec/software/qpOASES
2
http://www.cnsystems.at/product-line/cnap-monitor-500/
49
wave as an analog signal which is fed over a galvanic separation to the xPC
target. Setting up the measurement system takes a few minutes: when the
arm and finger cuffs are adjusted properly, the device is ready to use after
a short calibration phase. The device has to be recalibrated after one hour
of measurement, so that accuracy is warranted. Please refer to Kupke [6]
(p.5-6) for more details about the CNAPTM Monitor specifications.
Figure 5.1: CNAPTM Monitor 500 with arm and finger cuffs: non-invasive
continuous blood pressure measurement device used for all measurements
and control experiments.
As the CNAP device only outputs the raw blood pressure signal, the systolic
and the diastolic blood pressure have to be extracted separately. This is done
with an online peak detection routine extracting maxima (systolic blood
pressure) and minima (diastolic blood pressure) [6]. Once the peaks are
identified, heart rate calculation is performed.
5.1.3 Experimental design

Model validation
Three subjects (2 female, 1 male) aged between 20 and 35 years were measu-
red in total for model validation (table 5.1). The measurement protocol was
defined as illustrated in Figure 3.11. The identification part was designed
such that both the influence of stepping and the influence of tilting could
be analysed in supine as well as in tilted position. Note that that when the
stepping is activated or deactivated, the waiting time is not only 3 but 5
minutes. This is because of the slower dynamics of heart rate and blood
pressure in response to stepping.
50
Table 5.1: Healthy subjects participating in the model validation
MW MSW DH
Sex m f f
Weight 68 55 58
Control experiments
Five subjects (3 female, 2 male) aged between 20 and 35 years were measured
in total (table 5.2). For each of the five subjects three control experiments,
lasting 20 minutes each, were done. The first experiment was isolated heart
rate control, the second was blood pressure control (systolic and diastolic),
and the last experiment was combined control of all three physiological si-
gnals. The control experiments were preceded by an identification phase in
order to identify the unknown parameters and fit the model to the subject.
Table 5.2: Healthy subjects participating in the control experiments
PB MW LB RR ME
Sex m m f f f
Weight 90 68 65 63 62
This is done with an shortened identification measurement compared to mo-

del validation which lasts 11 minutes in total. First, the baseline values at
the supine position are calculated which is done by taking the average over
the last two minutes before the tilt. Similarly, the steady-state values for the
tilted position ( = 76 ) are calculated by taking the mean value of minutes 5
and 6 to account for the transient behaviour. Finally, the steady-state values
for the stepping are calculated by taking the mean of minutes 10 and 11. The
reason for the longer duration of the stepping part is the slower dynamics of
heart rate and blood pressure in response to stepping, i.e. it takes more time
to reach the steady-state. The identified values can be stated as follows
T
y = I PS PD (5.1)
+ T
y + = I + PS+ PD

(5.2)
T
y s = I s PSs PDs (5.3)
Figure 5.2 exemplifies the identification protocol in the lowermost plot and
the measured signals together with the simulated model response for subject
PB in the upper three plots.
51
90
HR [bpm]
80
70
60
0 2 4 6 8 10 12 14
Time [min]
160
sBP [mmHG]
140
120
0 2 4 6 8 10 12 14
Time [min]
dBP [mmHG]
80
60
0 2 4 6 8 10 12 14
Time [min]
fstep [steps/min]
[deg] /
50
0
0 2 4 6 8 10 12 14
Time [min]
Figure 5.2: Model identification (subject PB). The lowermost plot shows the
identification protocol. The upper three plots depict the measured signals
(green) together with the simulated model responses (blue).
52
5.2 Patients
5.2.1 Implementation
As the measurements were done at the hospital, the implementation had to
be adapted to local conditions. The ERIGO at the hospital, which is the
standard version delivered by HOCOMA, did not contain the same inter-
faces as the ERIGO at the SMS lab. So, one major issue was that control
commands had to be given by hand following the numbers on the Matlab
display. The inclination angle was set using a water-level and the stepping
frequency was adjusted using the ERIGO touchscreen. Transferring the cus-
tomised ERIGO from the SMS lab at ETH Zurich to Wald would probably
have been possible, but was not an option due to ethical reasons. In addition,
the manual control worked well and no further actions had to be taken.
The controller was implemented using a Simulink model reading raw blood
pressure data, extracting the physiological signals, and displaying the com-
puted control inputs on the laptop screen.
5.2.2 Blood pressure recording

Blood pressure recording was also done with the CNAPTM monitor just as it
was the case with healthy subjects. However, the blood pressure signal was
fed to a biosignal amplifier (USBamp from g.tec 3 : figure 5.3), from where it
could be routed to the laptop over a standard USB connection.
Figure 5.3: Biosignal amplifier USBamp from g.tec.
3
http://www.gtec.at
53
5.2.3 Experimental design
One patient was measured at the Z urcher Hohenklinik in Wald. Just like
with the healthy subjects, the unknown model parameters had to be calcula-
ted after the initial identification phase. Afterwards, isolated control of either
heart rate or blood pressure has been done. Different from the measurements
with healthy subjects, control with patients was done with only one setpoint.
One reason is that patients usually have large drifts in physiological values
and the model has to be readjusted every now and then. Another reason is
that two setpoints only make sense to test the step response of the control
system, but is meaningless for stabilising the cardiovascular system of a neu-
rological patient. From a clinical point of view, it is only important to control
to one setpoint which may be defined by the attending doctor. Furthermore,
the systems step response has already been tested with healthy subjects.
54
Chapter 6
Results
This chapter describes the results of the control experiments done at the
SMS lab with healthy people and with neurological patients at the Z
urcher
Hohenklinik in Wald.
6.1 Healthy subjects

6.1.1 Heart rate control
Figure 6.1 shows the results from the heart rate control experiment. The
subject showed the standard physiological reactions to tilting and stepping:
heart rate has risen with increasing tilt angle and decreased in the long
run with active stepping.
At the beginning it took some time until the heart rate had risen to the
desired value. This is not only because of the heart rate dynamics but also
because the controller increased the inclination angle rather slowly due to
high values in the weighting matrix R. The next interesting feature is the
activation of the stepping prior to the reference step. This happens because
of the anticipative nature of the model predictive controller which detects
the reference step in advance and includes it in the optimisation procedure.
When the step is there after 10 minutes, the controller switches the state-
space descriptions from the linearisation around the first set-point to the
linearisation around the second set-point. It is satisfying to see that the
controller is robust to this immediate switch.
6.1.2 Blood pressure control

The blood pressure control experiment that is plotted in Figure 6.2 has been
done with a different subject than the heart rate control. However, this sub-
55
85
HR [bpm] 80
75
70
65
60
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
fstep [steps/min]
60
[deg] /
40
fstep
20
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure 6.1: Healthy subjects (MW): heart rate control.
ject also showed the standard physiological reactions to tilting and stepping:
Systolic and diastolic blood pressure increased with the tilting angle, the
stepping mechanism mainly increased systolic blood pressure and had little
effect on diastolic blood pressure.
The slow rise of the tilting angle in the beginning of the experiment is analog
to the previous experiment with heart rate control. After 3 minutes, the
stepping was activated because systolic blood pressure was still too low and
the angle was already quite high. As a result, systolic blood pressure increa-
sed and reached the desired reference value. After 5 minutes, there was a
huge drop in systolic blood pressure which is probably due to a detection
error or a movement artefact 1 . It is good that the controller was robust to
this drop and did not produce severe counteractions. In the second part of
the experiment, control performance is very satisfying and combined control
of systolic and diastolic blood pressure seems feasible.
6.1.3 Combined heart rate and blood pressure control

Again, for the last experiment, a different subject has been chosen because
the according results nicely illustrates performance of combined control. The
subject showed normal physiological responses to tilting and stepping as it
1
The artefact has been cut off for calculation of mean and standard deviation.
56
140
sBP [mmHG]
120
100
0 2 4 6 8 10 12 14 16 18 20
Time [min]
dBP [mmHG]
80
70
60
50
0 2 4 6 8 10 12 14 16 18 20
Time [min]
fstep [steps/min]
80

[deg] /
60
40
fstep
20
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure 6.2: Healthy subjects (PB): blood pressure control.
has also been the case for the previous two subjects.
Figure 6.3 reveals that combined control of heart rate and blood pressure is
difficult. It can be seen that after a few minutes a quite stable situation has
been built up where the heart rate was too low and systolic blood pressure
was too high. Such a situation can not be handled by the controller. An
increase of the inclination angle would make sense for heart rate, but also
further increases systolic blood pressure. Similarly, a decrease of the angle
would not lower the errors, either. The angle therefore settles at a value
where the errors in heart rate and systolic blood pressure are minimal. An
increase of the stepping frequency makes even less sense because heart rate
would be further decreased and systolic blood pressure further increased.
6.2 Patients
One patient had the opportunity to experience the latest kind of ERIGO
therapy. Based on the above findings, priority was set to blood pressure
control because from a clinical point of view it is more important than heart
rate. Figure 6.4 shows a blood pressure control experiment of a neurological
patient lasting 30 minutes. The patient showed the standard pathophysio-
57
[bpm] 80
HR
60
0 2 4 6 8 10 12 14 16
Time [min]
150
[mmHG]
sBP
100
0 2 4 6 8 10 12 14 16
Time [min]
[mmHG]
80
dBP
60
0 2 4 6 8 10 12 14 16
Time [min]
fstep [steps/min]
[deg] /
fstep
50
0
0 2 4 6 8 10 12 14 16
Time [min]
Figure 6.3: Healthy subjects (ME): combined heart rate and blood pressure
control.
logical reaction which means that blood pressure dropped with increasing
tilting angle and rised with active stepping. These tendencies are visible in
figure 6.4 during the initial identification phase.
Already at the beginning of the experiment the tendency of the systolic blood
pressure to fall when tilting is clearly visible. The controller reacts to this
blood pressure drop by lowering the tilt angle and activating the stepping
mechanism. After 20 to 21 minutes, systolic blood pressure has been sta-
bilised again and even exceeds the reference value. That is the reason why
the stepping frequency is decreased a little in order to compensate for this.
As the experiment went on, stepping frequency was steadily increased which
indicates that the the patients cardiovascular system got more unstable over
time and blood pressure would have fallen without intervention. At the end
of the experiment, there is a sudden drop in blood pressure which is probably
because of the doctor and therapists that entered the room at that time and
set the patient under stress. The controller reacted accordingly and tried
to compensate this by increasing the stepping frequency and lowering the
tilting angle.
58
120
sBP [mmHG]
110
100
0 5 10 15 20 25 30 35 40 45
Time [min]
90
85
dBP [mmHG]
80
75
70
65
0 5 10 15 20 25 30 35 40 45
Time [min]
80
fstep [steps/min]

60
[deg] /
40
fstep
20
0
0 5 10 15 20 25 30 35 40 45
Time [min]
Figure 6.4: Patients: blood pressure control. The first 14 minutes depict the
identification phase. The control experiment starts at minute 15.
59
6.3 Controller performance
Table 6.1 summarises mean errors e and standard deviations for all control
experiments with healthy subjects and table 6.2 presents the results for the
measured patient.
Table 6.1: Healthy subjects: controller performance
Heart rate [bpm] Blood pressure [mmHg]

e sBP: e sBP: dBP: e sBP:
MW -0.61 3.05 -1.35 1.92 -2.17 2.11
PB -0.26 4.36 1.81 3.09 -0.98 3.15
LB 0.21 3.18 7.37 2.76 -2.12 2.98
RR -0.73 2.44 3.64 2.18 -2.26 2.44
ME -2.26 1.98 5.76 3.63 -3.19 2.01
Mean -0.73 3.00 3.45 2.72 -2.14 2.54
Table 6.2: Patients: controller performance
Blood pressure [mmHg]

sBP: e sBP: dBP: e dBP:
Patient -1.15 3.56 -2.53 2.73
60
Chapter 7
Discussion
The goal of this thesis was to develop a new physiological controller for heart
rate, systolic and diastolic blood pressure. This controller has been tested
in different configurations 1 with healthy subjects. However, the final goal is
to use it both for patients with orthostatic hypotension in order to stabilise
their cardiovascular system and minimally conscious patients in the context
of the AWACON project 2 . So, the first step consisted of developing a model
of the human cardiovascular system that is not only capable of capturing the
healthy physiological response to tilting and stepping, but also the patho-
physiological response. The pathophysiological response to tilting is usually
characterised by a systolic blood pressure decrease when tilting which can be
compensated for by activating the stepping mechanism. This behaviour is
compatible with the introduced model. However, there are responses where
the model can not be fitted to the identified steady-state values, not even by
adjusting the fixed parameters described in table A.2. One example is when
heart rate decreases with rising tilting angle. Such a cardio-inhibitory res-
ponse has indeed been measured with one of the patients, and consequently
it was not possible to fit the model and do a control experiment. No other
situations have been encountered where a model fit would not have been
possible. Nevertheless, in some cases the identified steady-state values had
to be slightly adjusted as not all model conditions (appendix A.6) were ful-
filled. In the development phase of the model, some efforts have been made
to better adapt the model to the pathophysiological tilt response. One idea
was to lessen or even cut the sympathetic influence in the baroreflex model
in order to account for the diminished sympathetic actions on the efferent
pathways. First simulation results were satisfying, but the idea was dropped
1
heart rate control; blood pressure control (systolic and diastolic); combined control of
heart rate and blood pressure
2
http://www.sms.mavt.ethz.ch/research/projects/awacon
61
for the sake of consistency and because the standard model already captured
the described pathophysiological response.
Based on the model, an appropriate controller has been developed. Only

linear control has been considered, although there has once been the idea of
linearising around the current state and not about the current setpoint which
would have been a kind of non-linear control (exact linearisation). Due to
stability reasons, this thought was not pursued. Furthermore, as the system
is expected to operate near the setpoint, the linearisation will not deviate
much from the non-linear model.
A more important issue is observer performance. It was experimentally found
that the observer reliably converges to the actual values of heart rate and
blood pressure. This has been verified by comparing the estimated out-
put values with the measured ones. Despite of that, problems can occur,
if one or more of the three output signals leave the identified range. Small
overshoots are tolerated. However, if these overshoots become too large the
non-linear model can become unstable and subsequently, the non-linear pre-
diction update of the observer diverges as well and can not be stabilised by
the measurement update anymore (see chapter 4.1). In order to avoid that
the simulations aborts, the estimated states are reset when the system moves
out of bounds. It is clear, however, that this does not prevent the system to
diverge again unless heart rate and blood pressure come back into the iden-
tified range. In addition, the state resetting can lead to jumps in the control
signals which is definitely unwanted. Thus, if the measured blood pressure
drifts away too much, the best thing to do is aborting the simulation, recali-
brating the blood pressure device and identify the model with new baseline
values. Note that the response, i.e. the difference between maximal and
minimal values, usually stays the same. So for the new model identification,
only the baseline values need to be updated.
The experiments with isolated control of heart rate yielded acceptable re-
sults based on the performance values in table 6.1 and visual inspection of
the results. Figure 6.1 shows that especially during the second part of the ex-
periment, controller performance for isolated heart rate control is satisfying
although the inclination angle was in average quite low and sometimes in
saturation. Still the controller was able to regulate the heart rate to the
desired value because the control bandwith is successively enlarged by the
stepping control input.
Based on the control experiment with subject PB (figure 6.2) it can be stated
that isolated blood pressure control worked well. However, the performance
values of table 6.1 reveal that in average the control performance was worse.
62
Still, it must not have been expected that systolic and diastolic blood pres-
sure control will work as the results from model validation, concluding that
systolic blood pressure is hard to predict and model, were not encouraging.
Fortunately, for most healthy subjects, there is a general increasing tendency
of systolic blood pressure in response to tilting and stepping. As long as these
tendencies stay the same during the control experiment and systolic blood
pressure stays in the identified range, blood pressure control seems possible
not only for patients but also for healthy subjects.
Combined control of all three physiological signals was shown to be diffi-
cult in the previous chapter. In our opinion, this is not believed to only
originate from the fact that systolic blood pressure is hard to model as full
blood pressure control has been shown to work properly. Rather, the pro-
blem must be attributed to the control system structure: the smaller the
input to output ratio, the harder it becomes to control the system. Imagine,
that if there was a third control input lowering systolic blood pressure for
example, combined control would be easier. Further, it has to be emphasised
that the plant is a biological system which is definitely subject to many more
influences than just tilting and stepping. A higher plant-model mismatch
must therefore be assumed in comparison to technical systems which behave
more deterministically. Hence, it actually had to be expected that for our
system the input to output ratio of 2 to 3 was already too small causing the
control system to struggle. As already mentioned above, control performance
could be improved by adding control inputs which ideally act separately on
the three outputs. It will have to be investigated to what extent heart rate
and blood pressure can be influenced by auditory, visual, gustatory and ol-
factory stimuli. A second idea is to control heart rate and mean arterial
pressure instead of all three physiological signals. Small adaptations of the
model will allow to test if such a control yields acceptable results. Thirdly,
as an alternative, only blood pressure can be controlled, whereas heart rate
is observed by the controller. Only if the heart rate goes beyond predefined
boundaries, the according control error is considered by the controller in the
optimisation function. This enhanced blood pressure control strategy would
probably yield better performance results compared to standard combined
control. Furthermore, it will still be guaranteed that heart rate is kept near
or inside the predefined safety band.
63
64
Chapter 8
Conclusion and Outlook
Based on the experimental results it can be stated that isolated control of

heart rate and blood pressure (systolic and diastolic) for healthy subjects is
possible. In addition, blood pressure control has also shown to be feasible
with neurological patients at the hospital. Combined control of heart rate and
blood pressure has been tested with healthy subjects, but did not produce
satisfying results. Further investigations have to be taken in order to see if
combined control of mean arterial blood pressure and heart rate is possible.
Another possibility would be to adapt the control strategy. One approach
for example is to only control blood pressure, but still monitor heart rate. If
heart rate then exceeds certain bounds, the controller will take appropriate
actions.
In the future, it is hoped, that an intelligent system capable of monitoring
and manipulating physiological signals will be realised. Such a system would
be helpful for stabilising the cardiovascular system of bed-ridden patients,
has the potential to reduce medication and improves the overall quality of
rehabilitation.
65
66
List of Figures
1.1 Left: Schematic representation of the ERIGO device with the

three inputs. Right: ERIGO during therapy session. . . . . . . 2
2.1 Schematic representation of the human circulatory system.

Adapted from: http://www.ionwave.ca . . . . . . . . . . . . 5
2.2 Blood pressure regulation with the baroreflex loop. . . . . . . 8
2.3 The muscle pump mechanism stabilises the cardiovascular sys-
tem by efficiently reducing venous blood pooling and increa-
sing venous return by repeated contractions of the skeletal leg
musculature. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3.1 Inputs and outputs of the cardiovascular model . . . . . . . . 15

3.2 Simplified representation of the human cardiovascular system
used for model synthesis. Adapted from [32] . . . . . . . . . . 17
3.3 Hemodynamic timetable describing at which moment of the
heart beat each hemodynamic variable is evaluated. Source:
Akkerman [32] . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.4 Katonas baroreflex model for heart rate regulation [34]. The
neural input signal f (t) is divided in a sympathetic (bottom)
and parasympathetic part (top) where defines the borderline
between sympathetic and parasympathetic regulation. . . . . . 20
3.5 Simplified baroreflex model (based on Katona [34] and Akker-
man [32]): the two branches regulating heart rate have been
merged to one, a second branch has been added for regulation
of peripheral resistance. . . . . . . . . . . . . . . . . . . . . . 20
3.6 Simulation of a fast tilt-up without stepping . . . . . . . . . . 28
3.7 Simulation of a fast tilt-down without stepping . . . . . . . . . 29
3.8 Simulation of an activation of the stepping mechanism ( = 76 ) 30
3.9 Quasi static simulation without stepping . . . . . . . . . . . . 31
3.10 Comparison of steady-state behaviour. Left: HR as a function
of . Right: Diastolic BP as a function of . . . . . . . . . . 32
3.11 Model validation with subject MW . . . . . . . . . . . . . . . 33
67
3.12 Model validation with subject MSW . . . . . . . . . . . . . . 34
3.13 Model validation with subject DH . . . . . . . . . . . . . . . . 35
4.1 MPC overview . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

4.2 Controller simulation: The first part depicts the system res-
ponse to a step at minute 2. The second part shows the sys-
tem response to a disturbance in heart rate and systolic blood
pressure at minute 5. . . . . . . . . . . . . . . . . . . . . . . . 47
5.1 CNAPTM Monitor 500 with arm and finger cuffs: non-invasive
continuous blood pressure measurement device used for all
measurements and control experiments. . . . . . . . . . . . . . 50
5.2 Model identification (subject PB). The lowermost plot shows
the identification protocol. The upper three plots depict the
measured signals (green) together with the simulated model
responses (blue). . . . . . . . . . . . . . . . . . . . . . . . . . 52
5.3 Biosignal amplifier USBamp from g.tec. . . . . . . . . . . . . . 53
6.1 Healthy subjects (MW): heart rate control. . . . . . . . . . . . 56

6.2 Healthy subjects (PB): blood pressure control. . . . . . . . . . 57
6.3 Healthy subjects (ME): combined heart rate and blood pres-
sure control. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
6.4 Patients: blood pressure control. The first 14 minutes depict
the identification phase. The control experiment starts at mi-
nute 15. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
B.1 Healthy subject MW: heart rate control . . . . . . . . . . . . . 87

B.2 Healthy subject PB: heart rate control . . . . . . . . . . . . . 88
B.3 Healthy subject LB: heart rate control . . . . . . . . . . . . . 88
B.4 Healthy subject RR: heart rate control . . . . . . . . . . . . . 89
B.5 Healthy subject ME: heart rate control . . . . . . . . . . . . . 89
B.6 Healthy subject MW: blood pressure control . . . . . . . . . . 90
B.7 Healthy subject PB: blood pressure control . . . . . . . . . . . 90
B.8 Healthy subject LB: blood pressure control . . . . . . . . . . . 91
B.9 Healthy subject RR: blood pressure control . . . . . . . . . . . 91
B.10 Healthy subject ME: blood pressure control . . . . . . . . . . 92
B.11 Healthy subject MW: combined heart rate and blood pressure
control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
B.12 Healthy subject PB: combined heart rate and blood pressure
control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
B.13 Healthy subject LB: combined heart rate and blood pressure
control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
68
B.14 Healthy subject RR: combined heart rate and blood pressure
control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
B.15 Healthy subject ME: combined heart rate and blood pressure
control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
69
70
List of Tables
2.1 Literature summary. means no significant change, means

significant increase, means significant decrease. (Adapted
and completed with HR from [5]) . . . . . . . . . . . . . . . . 12
2.2 Literature summary. means no significant change, means
significant increase and means significant decrease . . . . . . 12
3.1 Standard steady-state values used for the model simulations:

stands for supine position ( = 0 , fstep = 0); + stands
for tilted position ( = 76 , fstep = 0); s stands for stepping
( = 76 , fstep = fstep,max ) . . . . . . . . . . . . . . . . . . . . 24
4.1 MPC glossary. . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

4.2 Entries of covariance matrices W and V . . . . . . . . . . . . 40
5.1 Healthy subjects participating in the model validation . . . . . 51

5.2 Healthy subjects participating in the control experiments . . . 51
6.1 Healthy subjects: controller performance . . . . . . . . . . . . 60

6.2 Patients: controller performance . . . . . . . . . . . . . . . . . 60
A.1 Cardiovascular model variables. . . . . . . . . . . . . . . . . . 75

A.2 Fixed cardiovascular model parameters. . . . . . . . . . . . . . 76
A.3 Unknown cardiovascular model parameters. . . . . . . . . . . 77
71
72
73
Appendix A
Model summary
(VV (k 1) VV 0 )R (k)
PR (k) = (A.1)
CV + kSC (k)
(VP (k 1) VP 0 )L (k)
PL (k) = (A.2)
CP
VA (k 1) VA0
PD (n) = (A.3)
CA
VP (k) = VP (k 1) + QR (k P ) QL (k) (A.4)
VP P (k) = VP P (k 1) + QR (k) QR (k P ) (A.5)
VA (k) = VA (k 1) + QL (k) QW (k) (A.6)
VV (k) = VV (k 1) + QW (k) QR (k) (A.7)
VT = VP (k) + VP P (k) + VA (k) + VV (k) (A.8)
QR (k) = R PR (k)I(k 1) (A.9)
QL (k) = L PL (k)I(k 1) (A.10)

I(k)
QW (k) = CA (PS (k) PV (k)) 1 exp (A.11)
R(k)CA
VV (k 1) VV 0 QR (k)
PV (k) = (A.12)
CV + kSC (k)
QL (k)
PP (k) = (A.13)
CA
PS (k) = PD (k) + PP (k) (A.14)
R (k) = 1 R sin (k) (A.15)
1 1

L (k) = e L L (k) + 1 e L (1 + L sin (k)) (A.16)
1 2
PB (k) = PS (k) + PD (k) B sin (k) (A.17)
3 3
74
B(k) = PB (k) + kP PP (k) kB kSB (k) (A.18)
BS (k) = min(B(k), Bc ) (A.19)
1 1

JBI (k) = e BI JBI (k 1) + 1 e BI B(k) (A.20)
1 1

JBR (k) = e BR JBR (k 1) + 1 e BR BS (k) (A.21)
I(k) = (JBI (k) + Bc ) + kSR (k) (A.22)
R(k) = (Bc JBR (k)) + RP (A.23)
A.1 List of variables
Table A.1: Cardiovascular model variables.
Variable Unit Description

B(k) [mmHg] Barosignal
BS (k) [mmHg] Sympathetic barosignal
I(k) [ms] R-R interval
JBI [mmHg] Filtered barosignal for regulation of I(k)
JBR [mmHg] Filtered symp. barosignal for regulation of R(k)
PB (k) [mmHg] MAP at the level of the baroreceptors
PD (k) [mmHg] Diastolic blood pressure
PS (k) [mmHg] Systolic blood pressure
PP (k) [mmHg] Pulse pressure
PR (k) [mmHg] Right atrial pressure
PL (k) [mmHg] Left atrial pressure
PV (k) [mmHg] Venous pressure
QL (k) [ml] Left stroke volume
QR (k) [ml] Right stroke volume
QW (k) [ml] Transported blood volume in periphery
R(k) [mmHg ms/ml] Peripheral resistance
VA (k) [ml] Arterial blood volume
VP (k) [ml] Blood volume in the lung
VV (k) [ml] Venous blood volume
L (k) [-] Gravitational stress factor for PL
R (k) [-] Gravitational stress factor for PR
(k) [deg] Tilt angle
(k) [-] Influence of stepping
75
A.2 List of parameters
The values in table A.2 are adapted from Akkerman [32]. The following
adjustments with regard to Akkerman have been made:
70
1. Vact ,VV 0 ,VP 0 and VA0 are scaled by weight of the subject (kV = m 5105
65
for male subjects, kV = m 5105 for female subjects.
2. CV , CP and CA have been adjusted to scale stroke volumes, left atrial

pressure and right atrial pressure to normal physiological values based
on [7] (p.419, p.420) (Q
L = QR = 70 ml, PL = 4 mmHg and PR =

3 mmHg)
Table A.2: Fixed cardiovascular model parameters.
Parameter Value Unit Description

Vact 1500 kV [ml] Total active blood volume
VV 0 2950 kV [ml] Zero pressure volume of veins
VP 0 160 kV [ml] Zero pressure volume of lung
VA0 495 kV [ml] Zero pressure volume of arteries
CV 156.75 [ml/mmHg] Vein compliance
CP 174 [ml/mmHg] Lung compliance
CA 1.75 [ml/mmHg] Arteries compliance
P 2 [-] Stroke volumes in pulmonary pipeline
B 19 [mmHg] Grav. stress factor for PB
R 0.4 [-] Grav. influence on right atrial pressure
L 0.4 [-] Grav. influence on left atrial pressure
6 [ms/mmHg] Baroreflex sensitivity on R-R interval
Bcr , Bc 0.85 [-, mmHg] Baroreflex boundary
step 40 [heart beats] Time const.: stepping
L 6 [heart beats] Time const.: left atrium
BI 4 [heart beats] Time const.: B(k) I(k)
BR 3 [heart beats] Time const.: BS (k) R(k)
Table A.3 summarises the unknown parameters that are calculated during
model identification.
76
Table A.3: Unknown cardiovascular model parameters.
Parameter Unit Description

R [ml/(mmHg ms)] Starling factor right
L [ml/(mmHg ms)] Starling factor left
RP [mmHg ms/ml] R in parasympathetic region
[ms/ml] Baroreflex sensitivity on peripheral resist.
kP [-] Pulse pressure contribution to barosignal
kB [mmHg] Threshold value for barosignal
kSC [ml/mmHg] Stepping: venous compl.
kSR [mmHG ms/ml] Stepping: peripheral resist.
kSB [mmHg] Stepping: baroreflex resetting
77
A.3 Model equations in non-linear state-space
form
1 1
x1 (k + 1) = e x1 (k) + 1 e
step
u2 (k)u1 (k)
step
(A.24)
1 1

x2 (k + 1) = e L x2 (k) + 1 e L (1 + L u1 (k)) (A.25)
L
x3 (k + 1) = x3 (k) + x9 (k) x2 (k) (x3 (k) VP 0 ) x5 (k) (A.26)
CP
L
x4 (k + 1) = x4 (k) + x2 (k) (x3 (k) VP 0 ) x5 (k) QW (k) (A.27)
CP
x5 (k + 1) = x7 (k) + Bc (A.28)
R x5 (k)
x6 (k + 1) = x6 (k) + QW (k) (x6 (k) VV 0 )(1 R u1 (k))
CV + kSC x1 (k)
(A.29)
(
L x5 (k)
x7 (k + 1) = x7 (k)e1/BI + kP x2 (k)(x3 (k) VP 0 ) kB +
CP CA
(A.30)

1 L x5 (k) 1
x2 (k)(x3 (k) VP 0 ) + (x4 (k) VA0 ) +
3 CP CA CA
)
2 1
B u1 (k) kSB x1 (k) 1 e1/BI

(x4 (k) VA0 )
3 CA
(
1/SR L x5 (k)
x8 (k + 1) = x8 (k)e + kP x2 (k)(x3 (k) VP 0 ) kB +
CP CA
(A.31)

1 L x5 (k) 1
x2 (k)(x3 (k) VP 0 ) + (x4 (k) VA0 ) +
3 CP CA CA
)
2 1
B u1 (k) kSB x1 (k) 1 e1/SR

(x4 (k) VA0 )
3 CA
x9 (k + 1) = x10 (k) (A.32)
R x5 (k)
x10 (k + 1) = (x6 (k) VV 0 )(1 R u1 (k)) (A.33)
CV + kSC x1 (k)
78
The peripheral flow QW (k) is defined as follows:

x5 (k + 1)
QW (k) = {PS (k) PV (k)} CA 1 exp
R(k)CA

L 1
= x2 (k)x5 (k)(x3 (k) VP 0 ) + (x4 (k) VA0 )
CP CA CA

R x5 (k) 1
(x6 (k) VV 0 ) (x6 (k) VV 0 )(1 R u1 (k)) CA
CV + kSC x1 (k) CV + kSC x1 (k)
( )
x7 (k) Bc
1 exp
[(Bc x8 (k)) + RP + kSR x1 (k)] CA
(A.34)
Output equations:
y1 (k) = x5 (k) (A.35)

1 x2 (k) (x3 (k) VP 0 ) L x5 (k)
y2 (k) = + (x4 (k) VA0 ) (A.36)
CA CP
1
y3 (k) = (x4 (k) VA0 ) (A.37)
CA
79
A.4 Steady-state equations in non-linear state-
space form
!
Steady-state equations: xi (n + 1) = xi (n) = xi
x1 : x1 = u2 u1 (A.38)
x2 : x2 = 1 + L u1 (A.39)
L
x3 : 0 = x9 x2 (x3 VP 0 ) x5 (A.40)
CP
L
x4 : 0 = x2 (x3 VP 0 ) x5 QW (A.41)
CP
x5 : x5 = x7 + Bc (A.42)
R x5
x6 : 0 = QW (x6 VV 0 )(1 R u1 ) (A.43)
CV + kSC x1
(
L x5
x7 : x7 = kP x2 (x3 VP 0 ) kB +
CP CA

1 L x5 1
x2 (x3 VP 0 ) + (x4 VA0 ) +
3 CP CA CA
)
2 1
(x4 VA0 ) B u1 kSB x1 (A.44)
3 CA
x8 : x8 = min(Bc , x7 ) (A.45)
x9 : x9 = x10 (A.46)
R x5
x10 : x10 = (x6 VV 0 )(1 R u1 ) (A.47)
CV + kSC x1
Output steady-state equations:
y1 : y 1 = I = x5 (A.48)

1 L x5
y2 : y 2 = PS = x2 (x3 VP 0 ) + (x4 VA0 ) (A.49)
CA CP
1
y3 : y 3 = PD = (x4 VA0 ) (A.50)
CA
80
For x4 and x6 we define the peripheral flow QW :

x5
QW = P S P V CA 1 exp
RCA

L 1
= x2 x5 (x3 VP 0 ) + (x4 VA0 )
CP CA CA

R x5

1
(A.51)
(x6 VV 0 ) (x6 VV 0 )(1 R u1 ) CA
CV + kSC x1 CV + kSC x1
( )
x7 Bc
1 exp
[(Bc x8 ) + RP + kSR x1 ] CA
81
A.5 Parameter identification
Part A
Part A is implemented in Matlab as biq.m. Procedure is adapted from
Akkerman [32].
Vector of unknowns: z = [R L kB kP RP ]
The parameter vector z will be identified from two steady-state measure-
ments y + (tilted) and y (supine).
+/
R = 1 R sin(+/ ) (A.52)
+/
L = 1 + L sin(+/ ) (A.53)
+/ +/
VA = C A PD + VA0 (A.54)
+/ +/ +/
PP = PS PD (A.55)
+/ +/
QL = C A PP (A.56)
+/ +/
QL = C A PP (A.57)
! +/ +/ +/
Q+/ = QW = QR = QL (A.58)
Q+
LI

= (A.59)
Q
LI
+
+/ +/
VP P = P QR (A.60)
+/ +/
Now, determine VV and VP :

R
1 R+ 0 0 +
VV V V0 VV 0 +
R R

V

L L
0 0 1 + V+ = VP 0 VP 0 +

L V L (A.61)
1 0 1 0 P

Vtot VP+P VA+
VP
0 1 0 1 Vtot VPP VA
+/ +/
+/ (VV VV 0 )R
PR = (A.62)
CV
82
+/ +/
+/ (VP VP 0 )L
PL = (A.63)
CP
QR
R = (A.64)
PR I
QL
L = (A.65)
PL I
+/ +/
+/ (VV VV 0 QR )
PV = (A.66)
CV
+/ 1 +/ 2 +/
PB = PS + PD B sin(+/ ) (A.67)
3 3
Baroreflex:
I
B = (A.68)
(1 + Bcr )
Bc = Bcr B (A.69)
I+
B+ = Bc (A.70)

!1
+/
+/ I +/ QW
R = ln 1 +/ +/
(A.71)
CA CA (PS PV )
RP = R (A.72)
R+ RP
= (A.73)
Bc BS+
where BS+ = min(Bc , B + )
B + B PB+ + PB
kP = (A.74)
PP+ PP
kB = B + + PB+ + kP PP+ (A.75)
83
Part B
Part B is implemented in Matlab as id2.m. The procedure is based on the
non-linear steady-state equations (appendix A.4).
In part B, the stepping parameters kSC , kSR and kSB are identified. The
steady-state measurement of the output variable y s at maximum tilt angle
and with active stepping will be needed. First the steady-state variables x1 ,
x2 , x3 , x4 and x5 can directly be inferred from the inputs u = (sin(76 ) 1)T
and outputs y s .
x1 : x1 = us2 us1 (A.76)

x2 : x2 = 1 + L us1 (A.77)
y1 : x5 = y1s (A.78)
CA CP (y2s y3s )
y2 : x3 = + VP 0 (A.79)
(1 + L us1 )L y1s
y3 : x4 = CA y3s + VA0 (A.80)
The other steady-state variables and the unknown stepping parameters can
be calculated using the remaining steady-state equations and the total blood
volume constraint.
x3 : 0 = x9 CA (y2s y3s ) (A.81)
x4 : 0= CA (y2s
y3s )
QW (A.82)
s
x5 : y1 = x7 + Bc (A.83)
1 2
x7 : x7 = kP (y2s y3s ) kB + y2s + y3s B us1 kSB x1 (A.84)
3 3
x8 : x8 = min(Bc , x7 ) (A.85)
R y1s
x10 : x10 = (x6 VV 0 )(1 R us1 ) (A.86)
CV + kSC x1
Volume : Vtot = V V + V P + V P P + V A
= x6 + x3 + P x9 + x4 (A.87)
With the definition of QW (A.34), (A.82) becomes
(
R y1s

(y2 y3 ) = y2 (x6 VV 0 ) (x6 VV 0 )(1 R us1 )
s s s
CV + kSC x1
) ( )
1 x7 Bc
1 exp
CV + kSC x1 [(Bc x8 ) + RP + kSR x1 ] CA
(A.88)
84
The unknown stepping parameters can now easily be calculated from (A.84), (A.86)
and (A.88):

s s 1 s 2 s s 1
kSB = x7 + kP (y2 y3 ) kB + y2 + y3 B u1 (A.89)
3 3 x1
(x6 VV 0 )(1 R us1 )R y1s

1
kSC = CV (A.90)
x9 x1

x 7 B c 1
kSR = s s
((Bc x8 ) + RP ) (A.91)
(y y )
ln 1 2 3 C x1
y2s P V A
where

R x5 1
P V = (x6 VV 0 ) (x6 VV 0 )(1 R us1 )
CV + kSC x1 CV + kSC x1
(A.92)
A.6 Model constraints

The model only produces meaningful results if certain constraints on the
model parameters are fulfilled. A basic assumption for example is that heart
rate will always increase when tilting. The following conditions need to be
checked before doing any simulation or control experiment in order to avoid
unexpected results.
Constraint 1: R+ > R
The peripheral resistance is bigger in the tilted position than in the
supine position.
1Q
R+ I + ln C (P
A S PV )
= + >1 (A.93)
R 1Q
I ln C (P + +
P )
A S V
Constraint 2: kP > 0
Negative values for kP are unphysiological.
I I +

31 (PS PS+ ) 23 (PD PD+ ) B sin +
kP = >0 (A.94)
(PS PD ) (PS+ PD+ )
Constraint 3: B > Bc , B + < Bc and B + 0

The borderline for parasympathetic and sympathetic regulation Bc
85
must be between the extreme values B and B + .
Bcr < 1 (A.95)

+
I
Bcr > (A.96)
2I
I+
I+
Bcr (A.97)
I I+
+/ +/
Constraint 4: PR > 0 and PL >0
1 1
L > (A.98)
sin +
1 1
R > (A.99)
sin +
where
(PS+ PD+ )I (VT VP 0 VV 0 VA0 CA PD P CA (PS PD ))
1 =
(PS PD )I + (VT VP 0 VV 0 VA0 CA PD+ P CA (PS+ PD+ ))
(A.100)
Constraint 5: PR+ < PR and PL+ < PL

The atrial pressures are bigger in the tilted position than in the supine
position.
(PS+ PD+ )I
<1 (A.101)
(PS PD )I +
Constraint 6: > 0
Negative values for , the sympathetic sensitivity factor on peripheral
resistance, is unphysiological.
(R+ R )
>0 (A.102)
2Bc I +
86
Appendix B
Summarised results
90
HR [bpm]
80
70
60
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
fstep [steps/min]
60
[deg] /
40
fstep
20
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.1: Healthy subject MW: heart rate control
87
90
HR [bpm]
80
70
60
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
fstep [steps/min]

60
[deg] /
40
20 fstep
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.2: Healthy subject PB: heart rate control
80
HR [bpm]
70
60
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
fstep [steps/min]
60
[deg] /
40
fstep
20
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.3: Healthy subject LB: heart rate control
88
80
HR [bpm]
70
60
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
fstep [steps/min]

60
[deg] /
40 fstep
20
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.4: Healthy subject RR: heart rate control
80
HR [bpm]
70
60
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
fstep [steps/min]
60
[deg] /

40 fstep
20
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.5: Healthy subject ME: heart rate control
89
fstep [steps/min] dBP [mmHG] sBP [mmHG]
100
90
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
70
60
50
0 2 4 6 8 10 12 14 16 18 20
Time [min]
[deg] /
50 fstep
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.6: Healthy subject MW: blood pressure control

140
120
100
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
70
60
50
0 2 4 6 8 10 12 14 16 18 20
Time [min]
[deg] /

50 fstep
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.7: Healthy subject PB: blood pressure control
90
sBP [mmHG]
130
120
110
100
0 2 4 6 8 10 12 14 16 18 20
Time [min]
dBP [mmHG]
80
60
0 2 4 6 8 10 12 14 16 18 20
fstep [steps/min]
Time [min]
[deg] /
50 fstep
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.8: Healthy subject LB: blood pressure control

130
120
110
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
60
0 2 4 6 8 10 12 14 16 18 20
Time [min]
[deg] /
50
fstep
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.9: Healthy subject RR: blood pressure control
91
120
100
80
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
60
40
0 2 4 6 8 10 12 14 16 18 20
Time [min]
[deg] /
fstep
50
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.10: Healthy subject ME: blood pressure control
90
[bpm]
80
HR
70
60
0 2 4 6 8 10 12 14 16 18 20
Time [min]
110
[mmHG]
100
sBP
90
80
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
[mmHG]
70
dBP
60
50
0 2 4 6 8 10 12 14 16 18 20
fstep [steps/min]
Time [min]
fstep
[deg] /
50
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.11: Healthy subject MW: combined heart rate and blood pressure
control
92
90
[bpm]
80
HR
70
60
0 2 4 6 8 10 12 14 16 18 20
Time [min]
[mmHG]
140
sBP
120
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
[mmHG]
70
dBP
60
50
0 2 4 6 8 10 12 14 16 18 20
fstep [steps/min]
Time [min]
[deg] /
50
fstep
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.12: Healthy subject PB: combined heart rate and blood pressure
control
80
[bpm]
HR
70
60
0 2 4 6 8 10 12 14 16 18 20
Time [min]
130
[mmHG]
sBP
120
110
0 2 4 6 8 10 12 14 16 18 20
Time [min]
90
[mmHG]
dBP
80
70
60
0 2 4 6 8 10 12 14 16 18 20
fstep [steps/min]
Time [min]
[deg] /
50
fstep
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.13: Healthy subject LB: combined heart rate and blood pressure
control
93
[bpm] 80
70
HR
60
50
0 2 4 6 8 10 12 14 16 18 20
Time [min]
120
[mmHG]
110
sBP
100
90
0 2 4 6 8 10 12 14 16 18 20
Time [min]
80
[mmHG]
dBP
70
60
50
0 2 4 6 8 10 12 14 16 18 20
fstep [steps/min]
Time [min]
[deg] /
50
fstep
0
0 2 4 6 8 10 12 14 16 18 20
Time [min]
Figure B.14: Healthy subject RR: combined heart rate and blood pressure
control
[bpm]
80
HR
60
0 2 4 6 8 10 12 14 16
Time [min]
150
[mmHG]
sBP
100
0 2 4 6 8 10 12 14 16
Time [min]
[mmHG]
80
dBP
60
0 2 4 6 8 10 12 14 16
fstep [steps/min]
Time [min]
[deg] /
fstep
50
0
0 2 4 6 8 10 12 14 16
Time [min]
Figure B.15: Healthy subject ME: combined heart rate and blood pressure
control
94
Bibliography
[1] R. J. Corcoran. Use it or lose it - the hazards of bed rest and inactivity.
Rehabilitation Medicine, 154:536538, 1991.
[2] D. K. Dittmer and R. Teasell. Complications of immobilization and bed

rest. Canadian Family Physician, 39:14281437, 1993.
[3] M. Wieser. Multi-modal awakening control for low-responsive pa-

tients. http://www.sms.mavt.ethz.ch/research/projects/awacon,
2011. Last visited: 26.04.2011.
[4] M. Wieser, R. M. Ruest, L. B utler, and R. Riener. Response and

control of heart rate via posture and motion. In Third International
Joint Conference on Biomedical Engineering Systems and Technologies
(BIOSTEC), 2010.
[5] D. K. Nguyen. Blood pressure modeling and control via posture and
motion. Masters thesis, ETH Zurich, 2009.
[6] T. Kupke. Control of blood pressure and heart rate via verticalization
and mobilization. Masters thesis, ETH Zurich, 2010.
[7] P. Deetjen, E. J. Speckmann, and J. Hescheler. Physiologie. Elsevier,

Urban & Fischer Verlag, 2005.
[8] V. E. Claydon, J. D. Steeves, and A. Krassioukov. Orthostatic hypo-

tension following spinal cord injury: understanding clinical pathophy-
siology. Spinal Cord, 44:341351, 2006.
[9] R. Klinke, H. C. Pape, and S. Silbernagel. Physiologie. Thieme Verlag,

2005.
[10] R. Hainsworth and Y. M. Al-Shamma. Cardiovascular responses to

upright tilting in healthy subjects. Clinical Science, 74:1722, 1988.
95
[11] S. Mukai and J. Hayano. Heart rate and blood pressure variabilities
during graded head-up tilt. Journal of Applied Physiology, 78:212216,
1995.
[12] H. Tanaka, B. J. Sjoberg, and O. Thulesius. Cardiac output and blood

pressure during active and passive standing. Clinical Physiology, 16:157
170, 1996.
[13] W. H. Cooke, J. B. Hoag, A. A. Crossman, T. A. Kuusela, K. U. O. Tah-

venainen, and D. L. Eckberg. Human responses to upright tilt: a window
on central autonomic integration. Journal of Physiology, 517.2:617628,
1999.
[14] Y. Yokoi and K. Aoki. Relationship between blood pressure and

heart rate variability during graded head-up tilt. Acta Physiol. Scand.,
165:155161, 1999.
[15] M. E. V. Petersen, T. R. Williams, C. Gordon, R. Chamberlain-Webber,

and R. Sutton. The normal response to prolonged passive head up tilt
testing. Heart, 84:509514, 2000.
[16] M. P. Tulppo, R. L. Hughson, T. H. Makikallio, K. E. Juhani Airaksi-

nen, T. Seppanen, and H. V. Huikuri. Effects of exercise and passive
head-up tilt on fractal and complexity properties of heart rate dyna-
mics. American Journal of Physiology - Heart and Circulatory Physio-
logy, 280:10811087, 2000.
[17] K. Toska and L. Walloe. Dynamic time course of hemodynamic responses

after passive head-up tilt and tilt back to supine position. Journal of
Applied Physiology, 92:16711676, 2002.
[18] T. Heldt, M. B. Oefinger, M. Hoshiyama, and R. G. Mark. Circulatory

responses to upright tilting in healthy subjects. Computers in Cardio-
logy, 30:263266, 2003.
[19] T. Heldt. Computational Models of Cardiovascular Response to Ortho-

static Stress. PhD thesis, Harvard - MIT Division of Health Sciences
and Technology, 2004.
[20] G. Colombo, R. Schreier, A. Mayr, H. Plewa, and R. Rupp. Novel tilt

table with integrated robotic stepping mechanism: Design principles and
clinical application. In Proceedings of the 2005 IEEE 9th International
Conference on Rehabilitation Robotics, 2005.
96
[21] S. Masuki, J. H. Eisenach, W. G. Schrage, N. M. Dietz, C. P. Johnson,
B. W. Wilkins, R. A. Dierkhising, P. Sandroni, P. A. Low, and M. J. Joy-
ner. Arterial baroreflex control of heart rate during exercise in postural
tachycardia syndrome. Journal of Applied Physiology, 103:11361142,
2007.
[22] S. Masuki, J. H. Eisenach, W. G. Schrage, C. P. Johnson, N. M. Dietz,

B. W. Wilkins, P. Sandroni, P. A. Low, and M. J. Joyer. Reduced stroke
volume during exercise in postural tachycardia syndrome. Journal of
[23] L. Chi, K. Masani, M. Miyatani, T. A. Thrasher, K. W. Johnston,

A. Mardimae, C. Kessler, J. A. Fisher, and M. R. Popovic. Cardio-
vascular response to functional electrical stimulation and dynamic tilt
table therapy to improve orthostatic tolerance. Journal of Electromyo-
graphy and Kinesiology, 18:900907, 2008.
[24] F. A. Ramirez-Marrero, N. Charkoudian, E. C. Hart, D. Shroeder, and

L. Zhong. Cardiovascular dynamics in healthy subjects with differing
heart rate responses to tilt. Journal of Applied Physiology, 105:1448
1453, 2008.
[25] S. Houtman, B. Oeseburg, R. L. Hughson, and M. T. E. Hopman. Sym-

pathetic nervous system activity and cardiovascular homeostasis during
graded head-up tilt in patients with spinal cord injuries. Clinical Auto-
nomic Research, 10:207212, 2000.
[26] J. M. Legramante, G. Raimondi, M. Massaro, and F. Iellamo. Positive

and negative feedback mechanisms in the neural regulation of cardiovas-
cular function in healthy and spinal cord-injured humans. Circulation,
103:12501255, 2001.
[27] J. L. Corbett, H. L. Frankel, and P. J. Harris. Cardiovascular responses

to tilting in tetraplegic man. The Journal of Physiology, 215:411431,
1971.
[28] T. Heldt, E. B. Shim, R. D. Kamm, and R. G. Mark. Computational

modeling of cardiovascular response to orthostatic stress. Journal of
[29] M.S. Leaning, H.E. Pullen, E.R. Carson, M. Al-Dahan, N. Rajkumar,

and L. Finkelstein. Modelling a complex biological system: the human
cardiovascular system: Model validation, reduction and development.
97
Transactions of the Institute of Measurement and Control, 5(2):8798,
1983.
[30] R. W. de Boer and J. M. Karemaker. Relationships between short-term

blood-pressure fluctuations and heart-rate variability in resting subjects
I: a spectral analysis approach. Medical and Biological Engineering and
Computing, 23:352358, 1985.
[31] R. de Boer, J. Karemaker, and J. Strackee. Relationships between short-

term blood-pressure fluctuations and heart-rate variability in resting
subjects II: a simple model. Medical and Biological Engineering and
Computing, 23:359364, 1985.
[32] E. Akkerman. Dynamics of blood pressure regulation under influence of

gravity. Dissertation, University of Amsterdam, 1991.
[33] R. W. de Boer, J. M. Karemaker, and J. Strackee. Hemodynamic fluc-

tuations and baroreflex sensitivity in humans: a beat-to-beat model.
American Journal of Physiology - Heart and Circulatory Physiology,
253:680689, 1987.
[34] P. G. Katona, G. O. Barnett, and W. D. Jackson. Computer simulation

of the blood pressure control of the heart period. In P. Kezdi, edi-
tor, Baroreceptors and hypertension, pages 191199. Pergamon, Oxford,
1967.
[35] D. Czell, R. Schreier, R. Rupp, S. Eberhard, G. Colombo, and V. Dietz.

Influence of passive leg movements on blood circulation on the tilt table
in healthy adults. Journal of NeuroEngineering and Rehabilitation, 1:1
13, 2004.
[36] S. V. Matalon and L. E. Farhi. Cardiopulmonary readjustments in pas-

sive tilt. Journal of Applied Physiology, 47:503507, 1979.
[37] Jonas Fisler. Model and response of the cardiovascular system to tilt
and leg movement. Semester Thesis, ETH Zurich, 2007.
[38] J. Lofberg, H. Peyrl, M. Baric, I. Fotiou, and M. Morari. Model predic-

tive control. Course handout, ETH Zurich, 2010.
[39] L. Wang. Model Predictive Control System Design and Implementation

Using MATLAB. Springer-Verlag London Limited, 2009.
98
[40] H.J. Ferreau, H.G. Bock, and M. Diehl. An online active set strategy
to overcome the limitations of explicit mpc. International Journal of
Robust and Nonlinear Control, 18:816830, 2008.
99

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Master Thesis

Modelling and control of the human

Submission: April 2011

2 Human cardiovascular system 5

8 Conclusion and Outlook 65

Keywords Orthostatic intolerance, cardiovascular modelling, model pre-

This thesis focuses on the cardiovascular aspects of bed-ridden patients, i.e.

A tilt-table therapy is aimed at reconditioning the patients cardiovascular

heart rate, respiration frequency, skin conductance, oxygen saturation, EEG

Human cardiovascular system

This chapter will give a short introduction to physiology and pathophysio-

2.1 Hemodynamic system

Right lung Left lung

Right Left heart

Figure 2.1: Schematic representation of the human circulatory system. Adap-

Cardiac output (CO) is calculated as the product of stroke volume and

Diastolic blood pressure (dBP ) is the minimal blood pressure that

Mean arterial pressure (M AP ) is defined as the integrated blood pres-

Central venous pressure (CV P ) is the pressure in the intrathoracic

2.2 Blood pressure regulation

Right lung Left lung

Regulate heart rate & Baro-

Regulate peripheral resistance

Figure 2.2: Blood pressure regulation with the baroreflex loop.

The cardiopulmonary reflex is another blood pressure regulating mechanism

2.3 Orthostatic reaction and muscle pump

2.4 Cardiovascular pathology

Altered baroreceptor sensitivity

Lack of skeletal muscle pump

Altered salt and water balance

Baroreceptor sensitivity which is typically reduced in SCI patients is in tight

2.5 Literature review

Table 2.1: Literature summary. means no significant change, means

responses will be done. Table 2.2 presents standard cardiovascular responses

year aetiology HR sBP dBP MAP

Table 2.2: Literature summary. means no significant change, means

In order to control physiological quantities such as blood pressure and heart

Figure 3.1: Inputs and outputs of the cardiovascular model

In order to develop a mathematical model of the human cardiovascular sys-

3.1 Hemodynamic system

Figure 3.2: Simplified representation of the human cardiovascular system

VP (k) = VP (k 1) + QR (k P ) QL (k) (3.4)

Based on the Frank-Starling law and the restitution properties of ventricular

QR (k) = R PR (k)I(k 1) (3.8)

3.2 Blood pressure regulation

a branch for regulation of the peripheral resistance as proposed by Akker-

3.3 Influence of gravity

3.4 Influence of stepping

The stepping mechanism acts on the cardiovascular system by activating the

Compression of the venous leg compartments leads to an increase of

The contracting skeletal muscles decrease expandability of the venous

The muscle pump alters the functionality of the baroreflex mechanism.

(k) now operates in an additive nature on peripheral resistance, venous

R(k) = (Bc BS (k)) + RP + kSR (k) (3.30)

3.5.1 Fast tilt-up and tilt-down

Figure 3.6: Simulation of a fast tilt-up without stepping

Figure 3.7: Simulation of a fast tilt-down without stepping

Figure 3.8: Simulation of an activation of the stepping mechanism ( = 76 )

Figure 3.9: Quasi static simulation without stepping

Figure 3.10: Comparison of steady-state behaviour. Left: HR as a function

Figure 3.11: Model validation with subject MW

Figure 3.12: Model validation with subject MSW

Figure 3.13: Model validation with subject DH