Cooling to 10 degrees C and treatment with Cyclosporine A improve cerebral recovery following prolonged hypothermic circulatory arrest in a chronic porcine model.
OBJECTIVE
This study was undertaken to assess whether cooling to 10 degrees C and/or treatment with Cyclosporine A (CsA) can reduce neurological injury during prolonged hypothermic circulatory arrest (HCA) in a chronic animal model.


METHODS
In this blinded study, 24 pigs (20-23 kg) were randomized to HCA for 90 min at 20 degrees C (n=8), at 10 degrees C (n=8), or at 10 degrees C with 5 mg/kg CsA (n=8). CsA (or placebo) were given intravenously before and for 3 days after HCA. Hemodynamics and neurophysiological data were monitored periodically throughout the experiment and for 3 h after HCA, as well as intracranial pressure (ICP), which has been shown to correlate with outcome. Daily neurological/behavioral evaluation (mental status, coordination and appetite; 12=normal and 0=coma or death) was carried out until sacrifice on postoperative day (POD) 3.


RESULTS
Overall survival rate was 83.3%: one 20 degrees C control, two 10 degrees C controls, and one 10 degrees C/CsA pig died and were replaced. Basic hemodynamic data revealed no significant differences between groups. ICP differed significantly among the groups during the first 3 h postoperatively (P=0.003 by repeated measures ANOVA); it was higher in the 20 degrees C group than in the 10 degrees C/CsA or 10 degrees C control groups. Recovery of visual evoked potentials was significantly better in the 10 degrees C/CsA group than in the 10 degrees C control group; no recovery was seen by 3 h in the 20 degrees C control group. Postoperative behavioral scores also differed significantly between the groups, P=0.03: a good behavioral outcome--a score >9 on POD3--was more prevalent among CsA-treated pigs (75%) than among 10 degrees C controls (50%), or 20 degrees C controls (12.5%, P=0.06).


CONCLUSIONS
The data suggest that cooling to 10 degrees C and CsA treatment are both of benefit in improving cerebral recovery after HCA when compared with untreated 20 degrees C controls, and may be synergistic.
Strauch
Justus T
JT
Department of Cardiothoracic Surgery, Mount Sinai School of Medicine, New York University, New York, NY, USA. ju.strauch@gmx.de
Spielvogel
David
D
Haldenwang
Peter L
PL
Zhang
Ning
N
Weisz
Donald
D
Bodian
Carol A
CA
Tatton
Nadine A
NA
Griepp
Randall B
RB
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001930:Brain Injuries / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002467:Cell Nucleus / Q000473:pathology; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D006323:Heart Arrest / Q000150:complications* / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006624:Hippocampus / Q000473:pathology; D007036:Hypothermia, Induced / Q000379:methods*; D007427:Intracranial Pressure / Q000502:physiology; D009336:Necrosis / Q000473:pathology; D011897:Random Allocation; D013552:Swine
D016572:Cyclosporine