97776 PRF29210.1177/0267659113497776PerfusionTrummer et al.

Original Paper

Perfusion
2014, Vol. 29(2) 130­–138
Superior neurologic recovery after 15 minutes © The Author(s) 2013
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DOI: 10.1177/0267659113497776
extracorporeal life support system for prf.sagepub.com

optimized blood pressure and flow

G Trummer,1 K Foerster,1 GD Buckberg,3 C Benk,1 I Mader,2

C Heilmann,1 O Liakopoulos3 and F Beyersdorf1

Abstract
Objective: Sudden cardiac arrest is one of the leading causes of death. Conventional CPR techniques after cardiac arrest
provide circulation with reduced and varying blood flow and pressure. We hypothesize that using pressure- and flow-
controlled reperfusion of the whole body improves neurological recovery and survival after 15 min of normothermic
cardiac arrest.
Methods: Pigs were randomized in two experimental groups and exposed to 15 min of ventricular fibrillation (VF). After
this period, the animals in the control group received conventional CPR with open chest compression (n=6), while
circulation in the treatment group (n=6) was established with an extracorporeal life support system (ECLS) to control
blood pressure and flow. Follow-up included the assessment of neurological recovery and magnetic resonance imaging
(MRI) for up to 7 days.
Results: Five of the six animals in the control group died, one animal was resuscitated successfully. In the treatment group, 1/6
could not be separated from ECLS. Five out of the six pigs survived and were transferred to the animal facility. One animal
was unable to walk and had to be sacrificed 30 hours after ECLS. The remaining 4 animals of the treatment group and the
surviving pig from the control group showed complete neurological recovery. Brain MRI revealed no pathological changes.
Conclusion: We were able to demonstrate a significant improvement in survival after 15 minutes of normothermic car-
diac arrest. These results support our hypothesis that using an ECLS for pressure- and flow-controlled circulation after
circulatory arrest is superior to conventional CPR.

Keywords
CPR; resuscitation; ECLS; VA-ECMO; ECMO; cardiac arrest; ischemia-reperfusion injury

Introduction
Sudden cardiac arrest is one of the leading causes of
death worldwide.1-3 Despite increasing efforts in medical
staff training, cardiopulmonary resuscitation (CPR)
remains a difficult task which involves varying perfusion
pressures of the myocardium, brain and the whole-
body.4-6 Mortality rates of >70% are reported when CPR
pressure, flow, temperature and the reperfusate’s compo-
sition.9-12 Assuming that a severe ischemia-reperfusion
1Department of Cardiovascular Surgery, Heart Center Freiburg
University, Freiburg, Germany
2Section of Neuroradiology, Neurocenter of University Medical Center

Freiburg, Freiburg, Germany

is started 10 minutes (min) after cardiac arrest, with a
substantial rate of neurological impairment in the rare
case of survival.7,8
Circulatory standstill following cardiac arrest (CA)
causes whole-body ischemia followed by reperfusion
injury when the blood supply is re-established. However,
tissue and organs can be salvaged for much longer inter-
vals if the initial reperfusion is controlled in terms of
3David Geffen School of Medicine, University of California, Los Angeles,
CA, USA
Corresponding author:
Georg Trummer
Department for Cardiovascular Surgery
Heart Center Freiburg University
Hugstetterstrasse 55, 79106 Freiburg, Germany.
Email: georg.trummer@universitaets-herzzentrum.de
Trummer et al. 131
injury is the underlying cause of morbidity and mortality
after CPR, we gave special attention to the conditions of
reperfusion of the whole body after CPR. This issue has
been addressed by our group in the past years, demon-
strating superior survival and neurologic recovery after
90 min (hypothermic) and 15 min (normothermic) car-
diac arrest in pigs.13-16
Furthermore, extracorporeal life-support systems
(ECLS) have been demonstrated to be a useful tool in
improving survival after CPR.17-19 Since the restoration
of circulation and a sufficient blood supply to the organs,
especially the brain, are major aspects regarding CPR,20
the use of ECLS during and after CPR potentially enables
professional teams to gain control over reperfusion con-
ditions which have not yet been defined. We, therefore,
sought to explore the relevance of pressure- and flow-
controlled cardiopulmonary bypass after normothermic
cardiac arrest.
Material and Methods
All of the pigs (German landrace) received humane care
in compliance with the regulations for laboratory ani-
mals of the German Animal Protection Law, the
European Community (86/609/EC) and the
Regierungspraesidium Freiburg/Germany.
Experimental groups
Two experimental groups (control and treatment) with
induction of VF in both groups followed by 15 min of
normothermic cardiac arrest.
Control group (n=6):
CPR with open–chest access to the heart was initiated.
Treatment group (n=6):
No CPR. ECLS with pressure- and flow-controlled
circulation for 60 min.
Experimental protocol (control group)
Six pigs (Bodyweight 53.3 ± 2.3 kg) were premedicated
intramuscularly with midazolam (0.5 mg/kg) and ketamine
(20 mg/kg) and anesthetized with propofol (1%).
Endotracheal intubation was followed by volume-controlled
ventilation (Servo 900C, Siemens Elema, Visby, Sweden),
with the setting adjustment to normalize the PaO2 and
PaCO2 values. Anesthesia was maintained with fentanyl (2
µg/kg/h), vecuronium (0.2 mg/kg/h) and isoflurane 1.5-2%.
The arterial blood pressure was derived from the
carotid artery and a pulmonary artery catheter (Arrow
International, Reading, PA, USA) was placed. Heparin
was administered (300 IU/kg bodyweight (BW)) and VF
was induced with a 60 Hz (4.5 A) alternating current
(FI-10m, Stöckert, Sorin-Group Deutschland, Munich,
Germany) while the endotracheal tube was disconnected
from the ventilator during 15 min of CA.
Thereafter, advanced life support (ALS) was started for
20 min in an open chest setting via a post-sternal incision.
The animals were mechanically ventilated with 100%
oxygen and cardiac compression was performed at a
­frequency of 80/min. External shocks with 300 Joules
(Marquette Hellige CardioServ, Freiburg, Germany) were
repeated until a regular heart rhythm was established.
Inotropic and antiarrhythmic drugs were administered as
required. If a stable circulation was established, the ani-
mals were allowed to regain consciousness and were
weaned off the respirator. If circulation could not be re-
established during the 20 min ALS period, CPR was ter-
minated.
Experimental protocol (treatment group)
Six pigs (BW 54.5 ± 3.3 kg) were prepared as described
above. In addition to that, a 14 F cannula was placed in the
right femoral artery and a 24 F cannula in the right external
jugular vein (all cannulas: MEDOS Medizintechnik AG,
Stolberg, Germany) and connected to the ECLS. The ECLS
included tubing (3/8”), membrane oxygenator (Hilite
7000), venous reservoir (MVC 4030) and a diagonal pump
(Deltastream DP2; all MEDOS Medizintechnik AG,
Stolberg, Germany). Priming consisted of 700 ml Ringer’s
Solution (Jonosteril, Fresenius Kabi Deutschland GmbH,
Bad Homburg, Germany) containing 15000 IU heparin.
Following 15 min of CA, ECLS was maintained for 60
min, aiming at an arterial pressure (AP) of 70-80 mmHg
with a corresponding blood-flow of 80-100 ml/kg/min.
External defibrillation was attempted with 300 J and
repeated until a regular heart rhythm was established.
Arterial blood gas was monitored regularly (Blood Gas
Analyzer, Roche Cobas b121, Roche Diagnostics GmbH,
Mannheim, Germany) and during ECLS the PaO2 and
PaCO2 were adjusted to 200-300 mmHg and 40-50 mmHg,
respectively. Blood temperature during ECLS was regu-
lated to 37°C and ECLS was discontinued after 60 min.
Wounds were closed and the animals were allowed to
regain consciousness and were weaned off the respirator.
Postoperative Care
The animals were monitored for 7 days. MRI scans and
blood samples were obtained in deep general anesthesia
on day 7 and euthanasia was performed thereafter.
Parameters
Hemodynamics.  Cardiac output was determined using
the thermodilution technique, with derived parameters
such as cardiac index (CI), systemic and pulmonary
132 Perfusion 29(2)
Table 1.  Perioperative data after 15 min of cardiac arrest in 5/6 animals in the treatment group* and the only surviving animal in
the control group.
Number of defibrillations to terminate VF
Time to regain stable SR after start of ECLS (min)
ECLS (min)
Extubation after start of ECLS or CPR (min)
Discharge to animal facility after start of ECLS (hours)
*One animal was excluded due to intractable VF on ECLS.
CPR: cardiopulmonary resuscitation, ECLS: extracorporeal life support system, SR: sinus rhythm,
VF: ventricular fibrillation.
vascular resistance indices (SVRI/ PVRI). The number
of shocks, time to regain stable heart rhythm, total ECLS
time and mortality were registered.
Neurological Scoring
Neurological status was assessed before anesthesia and
every 24 hours until the end of the experiment and quan-
tified with a species-specific behaviour scale.21 A score of
0 is normal, 500 indicates brain death.
Biochemical data
Arterial blood was sampled at distinct time points.
Creatine kinase (CK-MB), serum aspartate aminotrans-
ferase (AST) and alanine aminotransferase (ALT) were
quantified in U/L plasma. Neuron-specific enolase (NSE)
was quantified using an Enzyme Immunometric Assay
(SynX Pharma Inc., Toronto, ON).
Magnetic resonance imaging (MRI)
Axial T2W turbo spin echo sequences and axial diffu-
sion-weighted MRI were performed on a 3T whole-body
scanner (TIM Trio, SIEMENS, Erlangen, Germany)
before and at the end of each experiment. A reduced
apparent diffusion coefficient (ADC) was taken as an
indicator of intracellular edema following acute isch-
emia. Contrast-to-noise ratios (CNR) of T2W-series and
maps of ADC from the selected brain regions of the final
MRI were compared to baseline images.
Statistical analysis
SPSS 16.0 (SPSS Inc, Chicago, Illinois, USA) was used.
After proven normality, a two-sided Student’s t-test for
equal variances and a Welsh test for unequal variances
were applied. A Bonferroni correction was performed.
Data were expressed as mean ± standard deviation (mean
± SD). P-values <0.05 were considered to be statistically
significant.
Treatment group Control group
12±4 4
3.8±1.3 5
62±1 no ECLS
164±9 184
3.3±0.3 3.6
Results
Mortality (Table 1)
Control group.  Two animals with open chest cardiac
compression regained regular heart rhythm during
CPR-ALS: one of these was weaned off the respirator
(Table 1) and showed an uncomplicated recovery. The
other animal was not responsive to high-dose inotro-
pic support and died 98 min after the start of CPR-
ALS. All other animals of the control group (4/6) died
due to circulatory failure.
Treatment group.  One animal could not be separated
from ECLS due to intractable VF. Five of the six animals
in the treatment group survived the intervention (Table 1).
Due to incomplete neurological recovery, one animal
had to be euthanized 30 hours after ECLS.
VF Induction and Termination (Table 1)
After induced VF, no animal in any group (n=12)
regained a regular heart rhythm spontaneously.
Control group.  In the control group, animals received
adrenaline (2-20 µg/kg bodyweight), lidocaine (2-8 mg/
kg bodyweight) and, if necessary, amiodaron (3 mg/kg
bodyweight) during resuscitation. One animal of this
group was successfully resuscitated. A regular heart
rhythm was established after 4 external shocks within 5
min after the start of CPR-ALS. A second animal of the
control group showed a stable heart rhythm after 8 exter-
nal shocks and 10 min of CPR-ALS, but died due to cir-
culatory failure 98 min after the start of CPR.
Treatment group.  The animals of the treatment group
received lidocaine until they regained a stable heart rhythm
(2-3 mg/kg bodyweight), but no inotropic medication dur-
ing ECLS. A regular heart rhythm was established in five
animals after 9 to 17 external shocks within 3.8±1.3 min
after the start of ECLS. One animal in the treatment group
died at the end of ECLS due to intractable VF (Table 2).
Trummer et al. 133

Table 2.  Development of Neurologic Deficit Scores (NDS) after intervention.

day 1 (24 h) day 2 (48 h) day 3 (76 h) day 4 -day 7

Treatment group (ECLS after cardiac arrest)
NDS Pig # 1 0 0 0 0
NDS Pig # 2 not applicable due to intractable VF on CPB  
NDS Pig # 3 20 0 0 0
NDS Pig # 4 0 0 0 0
NDS Pig # 5 145  
NDS Pig # 6 0 0 0 0
Control group (open chest cardiac compression)
NDS Pig # 1        10                   0             0            0
NDS Pig # 2 – 6 not applicable due to death after 20 min CPR-ALS
Neurologic deficit score (NDS) was 0 in 3 animals of the treatment group after 24 hours and in one pig after 48 hours. Pig # 5 was excepted from
this development showing an NDS of 145 after 24 hours. Though this animal regained full consciousness, accepting food and water, it could not stand
and walk 24 hours after the ischemic event. This animal was euthanized 30 hours after the ischemic event according to the protocol. In the control
group, one animal (pig # 1) was successfully resuscitated and showed undisturbed neurologic recovery with an NDS of 0 after 48 hours.

Table 3.  Biochemical data at baseline and endpoint after 20 min of CPR in the control group (open chest cardiac compression, n=6).

Baseline After 20 min CPR

Potassium (mmol/l) 3.65±0.36 6.68±1.57
Calcium (mmol/l) 1.43±0.05 1.39±0.05
Blood pH 7.44±0.03 7.11±0.11
Base excess (mmol/l) 3.2±2.3 –9.0±4.0
Hemoglobin (g/dl) 9.9±0.3 12.1±2.5
CK (U/l) 3026±3411 4717±3250
AST (U/l) 21.5±4.8 132.0±64.7
ALT (U/l) 41.2±12.8 47.5±14.2
NSE (Cg/l) 0.4±0.1 0.4±0.2
ALT: alanine amino transferase, AST: aspartate amino transferase, CG: control group, CK: creatine kinase, CPR: cardiopulmonary resuscitation, NSE:
neuron–specific enolase.

Neurological Deficit Score (NDS,Table 2) within the following 3 to 5 minutes to 19±4 mmHg and
then a final decrease to 5±3 mmHg. The pulmonary
Control group.  The only surviving animal in the control
artery pressure dropped to values corresponding to the
group showed an uncomplicated neurological recovery,
central venous pressure.
with a neurologic deficit score (NDS) of 10 after 24 hours
and zero after 48 hours until the end of the observation
Control group.  Mean arterial pressure values of 45±9
period at day 7 (Table 2). Further data were not applica-
mmHg were reached during CPR-ALS. The first blood
ble due to the high mortality.
samples were taken 3-5 min after the start of CPR-ALS.
Under these conditions, the animals of the control group
Treatment group.  Three of the 5 surviving animals
showed a metabolic acidosis with a pH of 7.16±0.05.
showed an NDS of zero 24 hours after surgery. One ani-
Five min after achieving a stable heart rhythm in two
mal revealed an NDS of 20 at 24 hours, but recovered
animals of this group, the pH further declined to
completely (NDS 0) after 48 hours. (Table 2). Another
7.04±0.06 (table 3). The MAP during cardiac arrest and
animal in the treatment group regained full conscious-
during the 5 minutes of CPR (9 mmHg and 35 mmHg,
ness, accepted food and water, but was unable to stand
respectively) were similar to those of the other animals
and walk 24 hours after surgery (NDS 145).
in the control group.

Hemodynamic data and pH during cardiac
arrest and resuscitation (Tables 3, 4 and 5)
The MAP dropped within 30 seconds after VF induction
to 8±1 mmHg in all animals, followed by a slight increase
Treatment group.  The MAP was between 70 and 80
mmHg during ECLS with a corresponding blood flow of
80-100 ml/kg/min. five of the six animals were abl to be
weaned off ECLS after 62±1 minutes without inotropic
support (Table 4).
134 Perfusion 29(2)

Table 4.  Hemodynamic data before and after ECLS and at the end of surgery in the treatment group (ECLS after cardiac arrest;
n=5)*.

Baseline End of ECLS End of Surgery

Heart rate/min 75±10 145±17 132±31
AP mean (mmHg) 79±5 89±13 81±11
AP systolic (mmHg) 100±6 110±14 106±11
AP diastolic (mmHg) 60±5 78±15 62±11
PAP mean (mmHg) 10±1 13±6 13±3
PAP systolic (mmHg) 18±3 23±5 24±3
PAP diastolic (mmHg) 3±1 5±5 5±5
CVP (mmHg) 2±3 4±2 3±3
PCWP (mmHg) 5±1 4±1 6±3
CI (l/min/m2) 4.1±0.6 4.3±0.4 4.9±1.1
SVI (ml/beat/m2) 55±12 29±4 38±7
SVRI (dyn x s x cm-5/m2) 1530±167 1711±275 1321±391
PVRI (dyn x s x cm-5/m2) 113±95 209±92 119±42
LVSWI (g x m/m2) 59±13 35±9 41±8
RVSWI (g x m/m2) 8±2 6±2 7±2
*N=1 animal was excluded due to intractable ventricular fibrillation on CPB.
AP: arterial pressure,CI: cardiac index, CK: creatine kinase, CVP: central venous pressure, ECLS: extracorporeal life support system, LVSWI: left
ventricular stroke work index, PAP: pulmonary artery pressure, PCWP: pulmonary capillary wedge pressure, PVRI: pulmonary vascular resistance
index, RVSWI: right ventricular stroke work index, SVI: stroke volume index, SVRI: systemic vascular resistance index.

Table 5.  Biochemical data before and after ECLS and at the end of experiment in the treatment group (ECLS after cardiac arrest;
n=4)*.

Baseline End of ECLS Day 7

Potassium (mmol/L) 3.8±0.2 4.8±0.3 3.9±0.2
Ionized calcium (mmol/L) 1.38±0.04 1.20±0.05 1.31±0.09
Blood pH 7.47±0.04 7.31±0.01 7.46±0.08
Base excess (mmol/L) 5.4±2.7 -4.0±1.8 5.5±1.9
Hemoglobin (g/dL) 9.8±0.6 9.0±1.0 9.1±1.0
CK (U/l) 2415±1289 8483±5852 3742±1422
AST (U/l) 35±10 61±42 43±17
ALT (U/l) 64±25 53±40 108±36
NSE (Cg/l) 0.3±0.2 0.3±0.1 2.3±1.5
*N=1 animal was excluded due to intractable ventricular fibrillation on ECLS and n=1 animal was excluded due to euthanasia on day 1 after surgery.
ALT: alanine amino transferase, AST: aspartate amino transferase, CK: creatine kinase, ECLS: extracorporeal life support system, NSE: neuron-specific
enolase.

The arterial blood gas started from normal values at
baseline (pH 7.47±0.04), indicating a metabolic acidosis
(pH 7.19±0.04) after 15 minutes of VF. At the end of
ECLS, a mild acidosis (pH 7.31±0.01) was present,
returning to baseline levels on day 7 (pH 7.46±0.08)
(table 5).
Renal function (Table 5)
Control group and treatment group.  Kidney function
was adequate in the survivors, with sufficient diuresis
without diuretics. All surviving animals showed physi-
ological hematocrit and potassium values during the
observation period (Table 5).
Biochemical data (Tables 3 and 5)
Control group.  Animals in the control group showed a
metabolic acidosis after 20 min of CPR-ALS. AST values
were slightly elevated after 20 min of CPR in this group
(p<0.05, Table 4). The only surviving animal in the con-
trol group exhibited slightly elevated ALT values after 7
days (105 U/l versus baseline 63 Ul/l) and a tendency to
increased NSE (0.6 µg/l at day 7 vs. 0.4 µg/l at baseline).
Base excess, pH, AST and all other biochemical data
returned to values close to baseline at the end of experi-
ment at day 7 in this animal.
Treatment group.  Animals in the treatment group
showed slightly elevated ALT values at the end of the
Trummer et al. 135
experiment after 7 days compared to baseline (p<0.05,
Table 5). Following intramuscular injection, CK was
still elevated at baseline blood samples and during the
experiment. Neuron-specific enolase remained at base-
line levels at the end of ECLS, with increased values at the
end of the experiment after 7 days (p<0.05, Table 5).
MRI (Figure 1)
Control group.  The only surviving animal of the control
group was measured with MRI 7 days after surgery. The
ADC and T2-weighted sequences did not reveal any evi-
dent pathology (Figure 1(a)).
Treatment group.  MRI was performed in 4 animals of
the treatment group after 7 days with no significant dif-
ferences in the CNR of T2-weighted images and ADC
maps from the defined brain regions compared to base-
line (Figure 1(b)). In the one animal of the treatment
group displaying incomplete recovery, MRI was per-
formed after 30 hours, revealing reduced ADC and a sig-
nal increase on T2-weighted images in the frontal lobe
and cerebellum (Figure 1(c)).
Comment
We compared survival and neurological recovery in pigs
after 15 min of normothermic CA with resuscitation by
open chest cardiac compression versus ECLS and were
able to demonstrate superior survival in the ECLS group.
There is a paucity of published reports of a survival
model in higher vertebrates after extended periods of
normothermic circulatory arrest. Schratter et al. reported
on results from a similar model in pigs with cardiac
arrest with subsequent CPR.22 In their study, 7 of 8 ani-
mals survived after 10 min of circulatory arrest, with a
significant decrease in survival after 13 min of cardiac
arrest. In another study, they investigated the effect of
cerebral hypothermia after 15 min of cardiac arrest fol-
lowed by CPR and ECLS with improved survival, but
considerable neurologic deficits in the surviving ani-
mals.23 Earlier, Kano et al. demonstrated that dogs can
survive after 15 min of normothermic CA.24 As in our
study, conventional CPR was omitted and ECLS via the
femoral vessels was initiated, but arterial blood pressure
showed higher systolic pressure values (~150 mmHg)
during ECLS. All animals receiving ECLS survived and
substantial neurologic recovery was reported with a
mean NDS of 146 after 24 hours.24 Although neurologic
recovery in their study was incomplete, they demon-
strated the advantage of ECLS after normothermic circu-
latory arrest, impressively.
To simulate the course of sudden cardiac arrest in
humans, we investigated conventional CPR in pigs.25 In
these experiments, primary CPR-ALS was unsuccess-
ful in 35% of the animals while the remaining 65%
subsequently required ECLS due to circulatory instabil-
ity, mainly caused by persistent VF. Survival was 71%
when defibrillation was successful during the first 10
min on ECLS and mortality was 100% when VF persisted
on ECLS.25 The high mortality rate caused by cardiac
dysfunction in those experiments matches the results
attained in our current control group. Furthermore, the
chosen animal model simulates the course of patients
with CPR-treated CA and subsequent concomitant poor
survival and neurologic recovery.26-28
The surviving animals were assessed for their neuro-
logical recovery. Within the neurological evaluation, the
ability to walk is a fundamental measure of recovery. In
our treatment group, 4/5 animals could walk without
help within the first 48 hours after global ischemia. One
animal in the treatment group failed to demonstrate such
recovery. MRI after 30 hours showed increased CNR on
T2-weighted images with decreased ADC. Ischemia or
profound cerebral hypoperfusion in pigs has not been
addressed so far in the literature, thus, a substantial gap
in interpreting our MRI data must be stated.
The control group simulated the usual clinical course
of sudden CA in humans, followed by CPR. External
chest compression in the pig with its latero-lateral
flattened chest is difficult, potentially leading to a pro-
longed period of low-flow/low-pressure persisting dur-
ing CPR. Therefore, we performed CPR-ALS in the
control group, applying open chest cardiac compression
with a MAP of ~45 mmHg during CPR. An adequate
perfusion pressure may be the precondition for the
achievement of a regular heart rhythm during CPR.
Consequently, all animals of this group were able to be
converted in a temporary regular heart rhythm. The ani-
mals of the control group needed a lower defibrillation
rate than the animals of the treatment group, possibly
due to the reason that continuous cardiac compression
interfered with frequent defibrillation. Otherwise, time
to regain a stable heart rhythm was extended compared
to the treatment group. Finally, prolonged circulatory
failure led to a high-grade rhythm disorder and the ani-
mals died. Of note, one animal in the control group was
able to sustain a sufficient blood pressure and could be
finally weaned off inotropic support. The pig showed no
neurological anomalies after 48 hours. It may be specu-
lated that CPR in this animal was comparably short com-
bined with an early return of a regular cardiac rhythm.
This might serve as an advantage towards a regular
blood-flow of the brain and the heart supporting this
recovery.
All surviving animals of both groups showed a notice-
able disparity between brain imaging and functional neu-
rological parameters as reflected by the NDS. Examination
of the brain revealed that the hippocampal areas showed
mild morphological changes, an observation consistent
with the literature.29,30 The hippocampal areas are
reported to have fewer perfused blood vessels than the
136 Perfusion 29(2)

Figure 1.  Magnetic Resonance Images.

Magnetic Resonance Imaging with focus on the frontal lobe: (a) The only surviving animal of the control group and (b) one representative pig (# 4)
of the treatment group. Figures a, and b are illustrating the morphological status of selected brain regions 7 days after normothermic cardiac arrest
without evident pathology. (c) Pig # 5 of the treatment group with neurological abnormalities. Note the intensity changes (white arrows) 30 hours
after normothermic cardiac arrest, attributed to an intracellular edema after acute ischemia of the brain.
Legend to the enclosed movie, (supplementary material will appear online with this article).
Impressions of one animal (# 3) in the treatment group during the 7-day course of the experiment: The film shows the “dead pig” after 15 min of
circulatory arrest without CPR; assisted attempts to get up 16 hours after intervention followed by further recovery at 36 hours with slight visible
neurological impairment. The last scene shows the neurological status beyond 48 hours up to 7 days with a complete functional recovery of the animal.

cerebral cortex.31 With respect to a cerebral low-flow or
low-pressure situation, which may occur during CPR,
this anatomical peculiarity may enhance a no-reflow phe-
nomenon, aggravating hippocampal alterations.32
This animal model’s study design contains certain
limitations, i.e., (1) We used volatile anesthetics and
propofol, which are known to be neuroprotective.33,34 An
experimental protocol to simulate sudden death was
only possible using general anesthesia. To ensure a
superficial, but sufficient level of anesthesia, an electro-
encephalograph (EEG) was monitored in pilot studies
(unpublished data); (2) We had to use juvenile animals to
guarantee mobility and a manageable weight during the
experimental course. However, the brains of juvenile ani-
mals possess higher ischemic tolerance.35 (3) We used
heparin for systemic pre-arrest anticoagulation, but hep-
arin potentially shows cardioprotective effects and
can improve survival and neurologic recovery after
Trummer et al. 137
experimental CA.36,37 We examined this major point of
objection in a small case study where we performed the
same ECLS experiments without preceding anticoagula-
tion. In summary, we found no positive effect of heparin
in regard to survival or neurologic recovery (in press).
In conclusion, we have successfully demonstrated
superior survival and neurologic recovery in an animal
model after 15 min of global normothermic CA. These
results support our hypothesis that omitting CPR after
CA, followed by reperfusion using ECLS to control
blood pressure and blood flow is superior to conven-
tional CPR. This observation is supported by our ear-
lier published work, showing that CPR followed by
ECLS correlates with high mortality and incomplete
neurological recovery,25 which is consistent with other
published studies.22,23,30 Our model allowed us to simu-
late near-realistic circumstances and CA outcomes.
We, therefore, believe that it provides outstanding
means of enhancing our understanding of the effects
of ECLS in the context of global ischemia after CA.
This may open the door for better survival and the
neurological recovery of patients requiring acute cir-
culatory support.
Declaration of conflicting interest
C. Benk, F. Beyersdorf and G. Trummer hold shares in
ResuSciTec Ltd. The other authors declare no conflict of interest.
Funding
This research received no specific grant from any funding
agency in the public, commercial or not-for-profit sectors.
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