Environmental Variables vs.

Physiological Control
• Environmental variables
– Pressure (760 mm-Hg)
• Hyperbaric vs. Hypobaric
– Temperature (22°C)
• Hypothermic vs. Hyperthermic
– Gas composition (78% N2, 21% O2)
• Hypoxic vs. hyperoxia
• Nitrogen saturation
– Gravity (1 x G = 9.8 m/s2)
• Hypogravity vs. hypergravity

1
2
High Altitude and Hypoxia
• Oxygen availability drops with
altitude
– 21% of absolute pressure
– O2 concentration in alveoli is what
counts
• Water vapor remains constant at 47 mm-Hg
• CO2 partial pressure drops with increased
respiration rates
• CO2 and H20 partially displace O2

3
4
 Compensation
Mechanisms
• System control – keep arterial O2
high
• Acute compensation for low PO2
– Hypoxic stimulation of arterial
chemoreceptors increases respiration
rate (i.e., breath faster)

5
 Compensation
Mechanisms
• Long-term compensation for low PO 2
– Chemoreceptor mechanism further
increases due to decrease in blood pH (days)
– Increased hematocrit and blood volume
(weeks)
• RBC production increases via erythropoietin
– PO2 sensed
– produced in kidneys
– acts on hematopoietic stem cells
• Blood volume under hormonal control of kidneys

6
7
8
9
10
11
 Compensation
Mechanisms
• Long-term compensation for low PO 2
– Increased diffusion capacity of lungs
• Increased capillary volume
• Increased lung volume
• Increased pulmonary pressure
– Increased capillarity in tissues
• Stimulate angiogenesis – growth of new
capillaries
– Feedback control in local tissue beds
– More effective in young, developing animals/people

12
 Compensation
Mechanisms
• Native adaptation to high
altitude
– All the same compensations of
acclimatization plus:
• Larger chest cavity
• Larger heart, especially right side
• Increased cellular efficiency to use O2

13
14
 Acute High Altitude Sickness
• Cerebral edema
– Hypoxia-induced vasodilatation, high
capillary pressure and edema – bad news.
• Pulmonary edema
– Vasoconstriction in pulmonary capillaries
leads to increased blood pressure in open
capillaries leading to edema – bad news.
• Breathing oxygen, especially under
pressure, can reverse symptoms

15
 Microgravity

• Gravity (as any force) can have

only two effects
1. Cause loading (usually with deformation)
2. Cause motion

16
 Space Flight and
Physiological Effects

17
 Neurovestibular Effects
• Affects about 50% of astronauts
• Symptoms begin around 1 hour –
recovery occurs around 1-3 days
• Relates to otolith organs in vestibular
apparatus
• Provoked by movements and/or odd
orientations
• Re-adaptation to 1G can also be
challenging
18
Vestibular Apparatus

19
20
21
 Theories on Space Motion
Sickness
• Fluid shift – Cephalic blood
movement
• Sensory conflict – Visual or
somatosensory vs. vestibular
cues
• Otolith organ asymmetry –
Differences in signal between
right and left sides
22
Treatment of Space Motion
Sickness
• Screening has proven ineffective
• Training strategies have been studied
• Drug combinations are commonly
used
– May delay adaptation
• Astronauts must tough it out

23
 Spaceflight Bone Loss
• Spaceflight (Unloading): 0.5-2% per
month
• Type I Osteoporosis (Post-
Menopause):
– 20% Tot, 5-7 years, 3-4% per yr.
• Type II Osteoporosis (Age related):
– ~1% per year, ongoing

24
 Bone Feedback Control
System
Hormones /
Cytokines

Bone Canaliculi Streaming

External Strain flows and SGPs or
mechanical network
Loads (Deformation) osteocytes direct strain
properties resistance deformed

Osteoclasts Osteoblasts
-
- + Osteocytes produce
Nitrous oxide /
Prostaglandins
Hormones /
Cytokines Osteocytes produce
sclerostin
25
 Skeletal Response to
Exercise
30

Sedentary Moderately
Active
Bone density (%)

Normal
Range
Lazy zone

-40 Spinal injury, immobolization, bed rest, space flight.

Changes only occur with significant habitual

changes in activities over several months
26
 Plasma Calcium Effects
• Calcium lost in urine - ~200mg/day
• Less calcium absorbed – lost in feces
• Plasma calcium increases in-flight
– Is normal shortly after landing
– May be at greater risk for kidney stones
• PTH is unchanged or decreased in
flight but elevates rapidly post-flight
(2x)
• Calcitonin is increased in flight (45%)

27
 Femur Mineral Mass

23.00
D
Placebo
22.00 OPG
D

21.00
Mass (mg)

D
SF SF
20.00

19.00

18.00

17.00

16.00
Flight AEM GC Viv GC

28
Elastic Strength

29
 Formation of Cortical Bone:
Bone Formation Rate
5.50
SF
5.00

4.50
En.BFR (0.001xmm2/day)

Placebo SF D
4.00
OPG SF
3.50

3.00 SF D
2.50

2.00

1.50

1.00
Flight AEM GC Viv GC

30
 Muscle Response to
Spaceflight
• Without resistive exercise for 2-3 months
– Leg muscle cross-sectional area ↓ ~30%
– Leg strength ↓ ~50%
– Shift occurs from slow to fast fiber types
– Back muscles become weak, soft tissues at risk of injury

Astronaut muscle fiber cross sections

Before Flight After Flight

From Space Research News, Winter, 2001 Dan Riley, The Medical
College of Wisconsin and Riley et al., 2002

31
 From Fitts, Riley and Widrick, (2000),
J Appl Pysiol, 89:823-839.

• Similar levels of muscle atrophy occur in mouse (12

days), rat (14 days) and human (17 days) soleus \
• Pattern of atrophy (Type I > Type II) may differ
between species

32
AEM Control SF

• 5-10 fold increase in

expression of MHC-IIx and –
IIb in soleus but not
plantaris or gastroc
• Similar shift to fast isoforms
as seen in other species

33
 Summary of Muscle Feedback

Circulating IGF-1

Insulin
IGF-1 +
External Muscle Transduction
Loads / Strength * Mechanical
Demands (PCSA) * Electrical Myostatin

- 
Protein
Synthesis 
Muscle
 -
Hypertrophy Protein
+ Degradation -
Muscle
Hyperplasia -
Satellite Cell
Activation 

34
 Astronaut Fitness -
Muscle
1. Reduce health risks to acceptable
limits
2. Maximize crew time availability for
mission • ISS crew expected to exercise
2.5 hours/day, 7 days per week
– Too much exercise can be a physical
and psychological burden

• Crews should not have to rely

on exercise
– Crisis or emergency situations
– Injury or illness

35
 Manned Mission to Mars - an
Ambitious Objective
MISSION TIMES MISSION TIMES
Outbound Outbound

313 days 180 days

Stay Stay Arrive Earth
12/11/20

40 days Arrive Earth Depart Mars 545 days

11/28/32
Return 1/25/32 Return

308 days Depart Earth 180 days

Arrive Mars
Total Mission 2/6/31 Sun
Total Mission Sun 11/7/18
 

661 days 905 days

Arrive Mars
12/16/31

Depart Earth
5/11/18

Depart Mars
6/14/20

Example Short-Stay Mission Example Long-Stay Mission

Preserving Astronaut health / fitness is major challenge

Credit : John Connolly and Kent Joosten
Presentation Title: Human Mars Mission Architectures and Technologies
Meeting: 1/6/2005 meeting of the Robotic and Human Exploration of Mars Roadmap Committee
36
 Hindlimb Suspension Effects

Muscle Mass
16

14
Soleus Wet Mass (mg)

12

10

2 Isolated Muscle
10.9 7.9 Strength
0
US P TS P

Whole Animal
Leg Strength

37
 Myostatin Blockade
Total Body Mass
27.00

26.50
US D
26.00

25.50
Body Mass (grams)

25.00 US P

24.50
TS D
24.00

23.50
TS P
23.00

22.50

22.00
0 2 4 6 8 10 12 14
Day of Study
38
Myostatin Blockade
Lean Body Mass
US > TS
P<0.001

D>P
P<0.001

39
 Motor Control

• Movement shifts from lower to

upper body
• Weight of limbs is eliminated
• Neck and hips become flexed

40
 Motor Control
• Effects of space flight include
– Short term
• Activation of extensor muscles is reduced
– Longer term
• Reflexes are affected – Achilles tendon tap
– Magnitude of movement is reduced
– Sensitivity to tap is reduced
– Amplitude of induced electrical response is reduced
– Post-flight
• Increased rate of tremors
• Time to make postural changes increases 2-3 x

41
42
 Factors governing cardiac
function and peripheral flow
• Cardiac Contractility (CC)
• End Diastolic Volume (EDV)
• Heart Rate (HR)
• Stroke Volume (SV)
• Cardiac Output (CO)
• Total Peripheral Resistance (TPR)
• Blood Pressure (BP) – Systolic and
Diastolic

• Control of cardiac function – intrinsic

and extrinsic
43
EDV

X SV
CC X CO
HR X BP

TPR

44
EDV

X SV
+
CC X CO
HR
+ X BP

TPR

45
46
- - - +
SNS PNS

+
Baroreceptors

EDV

X SV
+
+ X CO
CC
+ HR
+ X BP
-
TPR

47
 Short term response to space
flight (post-insertion to days)
• Post Insertion (minutes to hours)
– Loss of hydrostatic pressure
– Cephalic fluid shift
– Heart volume increases
– Increased EDV causes decreased HR and
cardiac contractility (CC)
– CVP decreases (unexpected response)
– Physiological response is comparable to
laying down (or standing on one’s head) in
1-G
48
Short term response to space
flight (post-insertion to days)
• Short Duration Response to
Microgravity (hours to days)
– Fluid shift maintained (facial puffiness,
engorged veins, sinus congestion)
– Increased diuresis
– Decreased water intake
– Loss of blood plasma volume and total
body water
– EDV decreases leading to increase in
HR over time

49
50
 On Orbit — Fluid Loss

Photo NASA
• Total loss of fluid from the
vascular and tissue spaces is
about 1-2 liters (about a 10%
volume change compared to
preflight)

51
Adapted from Lujan and White (1994)
 Long term adaptation to
space flight (weeks to
months)
• Continued increase in HR
• Decrease in baroreceptor reflex function
• Exaggerated response to LBNP (ΔHR)
• Cardiac system tends to stabilize
• Heart volume decreases (atrophy?)
• Heart rhythm disturbances (?)

• Disproportionate loss of red blood cell mass (?)

• Changes in vasculature (peripheral

resistance?)
– Increased venules and decreased arterioles

52
53
 Anemia of
Spaceflight Adapted from Lujan and White (1994)

• Erythropoietin is a
Landing

Erythropoietin
hormone which stimulates
red blood cells production
• The loss of fluid in the

Level
plasma concentrates red Normal Erythropoietin Level
blood cells
• The body responds by Launch
Microgravity
decreasing the
erythropoietin level
Mission Day

• Upon landing, when the fluid lost during spaceflight is

replaced, the red blood cells are diluted. A 10% decrease
in red blood cell count is observed. This causes the
phenomena called the “anemia of spaceflight”
• The body responds to this dilution by increasing the
erythropoietin level
54
 Post Flight Effects /
Recovery
• Orthostatic Intolerance (hours)
– Fluids shift to lower extremities
– EDV decreases causing increased HR
– Control of BP may not be adequate
– Syncope potential
– Weakened leg muscles results in
reduced venous valve blood pumping
action

55
 Tilt Test

• After 15-90 days of bed rest,

Documents MEDES
orthostatic intolerance is
evaluated by suddenly tilting
the subject from the supine
to the upright position
• Heart rate increases and
blood pressure decreases,
causing dizziness (pre-
syncope) or loss of
consciousness (syncope) Results after 5-16 day missions
• This orthostatic intolerance Pre- Pre- Non-pre-
also occurs in astronauts syncopal syncopal syncopal
when they try to stand
immediately after women men men
spaceflight
100% 20% 80%
56
Syncopy / Pre-syncopy Astronauts

• Low total peripheral resistance

before and after space flight
• Strong dependence of standing
stroke volume on plasma volume
(r=0.91 in pre-syncopal women vs.
r=0.17 in non-pre-syncopal men)
• Deficient norepinephrine release
response
57
 Post Flight Effects / Recovery

• Elevated HR (several days)

• Similar to disuse / sedentary effects
• Anemic-like conditions after
rehydration (RBC dilution)

• Duration of the recovery period

depends on duration of exposure to
reduced-gravity

58
 Countermeasures to
Cardiovascular
• In-flight Deconditioning
– Exercise
– Lower Body Negative Pressure Device (LBNP)
– Russian Chibis (LBNP) and Penguin (elastic
load) suits
– Neck cuff (positive or negative pressure)
– Thigh cuffs
• Pre-landing
– Saline fluid loading
– G-suits (positive pressure, lower torso)
– Recumbent seating (ISS crew members)
• Post-mission
– Exercise, time
59