Cooling to 10°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°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°C (n=8), at 10°C (n=8), or at 10°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°C control, two 10°C controls, and one 10°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°C group than in the 10°C/CsA or 10°C control groups. Recovery of visual evoked potentials was significantly better in the10°C/CsA group than in the 10°C control group; no recovery was seen by 3 h in the 20°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°C controls (50%), or 20°C controls (12.5%, P=0.06). Conclusions: The data suggest that cooling to 10°C and CsA treatment are both of benefit in improving cerebral recovery after HCA when compared with untreated 20°C controls, and may be synergistic.