Preserved brain morphology after controlled automated reperfusion of the whole body following normothermic circulatory arrest time of up to 20 minutes.
OBJECTIVE
Clinical outcomes following cardiac arrest (CA) and resuscitation remain a cause for concern. The use of Controlled Automated Reperfusion of the whoLe body (CARL) confers superior neurological outcome even after extended periods of CA. We aimed at investigating clinical outcome and brain morphology preservation when employing CARL following CA periods of 20 min.


METHODS
Twenty-eight pigs were allocated to four extracorporeal circulation treatment strategies; seven others served as magnetic resonance imaging (MRI) controls. In prompt cardiopulmonary resuscitation (CPR; n = 6), induced circulatory arrest was followed immediately by open cardiac massage of 15 min, thereafter by CARL for 60 min. In delayed CPR (n = 6), induced CA was maintained for 15 min, after that open cardiac massage of 10 min duration was performed prior to extracorporeal CPR (ECPR) of 60 min. Induced CA times of 15 min in the ECPR 15' group (n = 6) and CA of 20 min in the CARL 20' group (n = 10) were followed by ECPR of 60 min and CARL of 60 min, respectively, without prior CPR. Daily neurological deficit scoring (NDS) up to the seventh day, markers of cellular injury [alanine transaminase (ALT), aspartate transaminase (AST) and neuron-specific enolase (NSE)] and brain MRI were performed.


RESULTS
100% survival and normal NDSs were achieved in all animals in the prompt CPR and ECPR 15' groups. In CARL 20', nine animals survived. In contrast, only one animal in the delayed CPR group survived; three animals died within 24 h with a further two dying on Days 4 and 5, respectively. All markers of cellular injury were elevated in the delayed CPR group, ALT [38 (20.3) to 206 U/l (158.2); P = 0.0095], AST [26 (18.8) to 97 U/l (1965.8); P = 0.0095] and NSE [0.45 (0.25) to 7.95 µg/l (24.03); P = 0.0095]. In the ECPR 15' group, only NSE [0.45 (0.15) to 1.20 µg/l (2.40); P = 0.0065] remained elevated. In the CARL 20' group, differences in ALT [36 (10) to 53 U/l (20); P = 0.0005] and NSE [0.50 (0.40) to 1.5 µg/l (0.40); P < 0.0001] values were evident. T2-weighted MR images of the cerebellum [454 (28) to 495 mm2/s (55); U = 11; P = 0.0311], caudate nucleus [400 (59) to 467 mm2/s (42); U = 9; P = 0.0156], lentiform nucleus [377 (89) to 416 mm2/s (55); U = 11; P = 0.0311] and hippocampus [421 (109) to 511 mm2/s (58); U = 9; P = 0.0164] in the CARL 20' group showed higher signal intensities compared with controls. In delayed CPR, corresponding regions of interest on early apparent diffusion coefficient images showed a restricted diffusion.


CONCLUSIONS
In our experimental animal model of CA, CARL results in satisfactory survival at CA periods of 20 min despite detected enzyme and morphological changes. These changes did not translate to clinical neurological deficits.
Department of Cardiovascular Surgery, Heart Center Freiburg University, Freiburg, Germany itumeleng.taunyane@universitaets-herzzentrum.de.
Itumeleng C
IC
Taunyane
Department of Cardiovascular Surgery, Heart Center Freiburg University, Freiburg, Germany.
Christoph
C
Benk
Department of Cardiovascular Surgery, Heart Center Freiburg University, Freiburg, Germany.
Friedhelm
F
Beyersdorf
Department of Cardiovascular Surgery, Heart Center Freiburg University, Freiburg, Germany.
Katharina
K
Foerster
Department of Cardiovascular Surgery, Heart Center Freiburg University, Freiburg, Germany.
Heidi
H
Cristina Schmitz
Department of Cardiovascular Surgery, Heart Center Freiburg University, Freiburg, Germany.
Karin
K
Wittmann
Department of Neuroradiology, University Medical Center Freiburg, Freiburg, Germany.
Irina
I
Mader
Department of Neuropathology, University Medical Center Freiburg, Freiburg, Germany.
Soroush
S
Doostkam
University of Cooperative Education, Plauen, Germany.
Claudia
C
Heilmann
Department of Cardiovascular Surgery, Heart Center Freiburg University, Freiburg, Germany.
Georg
G
Trummer
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D016887:Cardiopulmonary Resuscitation; D004195:Disease Models, Animal; D005112:Extracorporeal Circulation / Q000379:methods; D006323:Heart Arrest / Q000150:complications / Q000628:therapy*; D002534:Hypoxia, Brain / Q000000981:diagnostic imaging / Q000517:prevention & control*; D008279:Magnetic Resonance Imaging; D015424:Reperfusion / Q000009:adverse effects / Q000379:methods*; D015427:Reperfusion Injury / Q000517:prevention & control; D013552:Swine; D013997:Time Factors
Circulatory arrest; Controlled Automated Reperfusion of the whoLe body; Extracorporeal CPR; Magnetic resonance imaging