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Eur J Cardiothorac Surg 2005;27:74-80
© 2005 Elsevier Science NL

Cooling to 10°C and treatment with Cyclosporine A improve cerebral recovery following prolonged hypothermic circulatory arrest in a chronic porcine model

^a Departments of Cardiothoracic Surgery, Neurosurgery, Mount Sinai School of Medicine, New York University, New York, NY, USA
^b Biomathematics, Mount Sinai School of Medicine, New York University, New York, NY, USA
^c Neurology, Mount Sinai School of Medicine, New York University, New York, NY, USA

Received 8 August 2004; received in revised form 21 October 2004; accepted 25 October 2004.

^* Corresponding author. Address: Department of Cardiothoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Erlanger Allee 101, 07747 Jena, Germany. Tel.: +49 3641 9322901; fax: +49 3641 9322902. (E-mail: ju.strauch{at}gmx.de).

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 (20–23kg) were randomized to HCA for 90min at 20°C (n=8), at 10°C (n=8), or at 10°C with 5mg/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 3h 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 3h 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 3h 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.

Key Words: Cerebral protection • Extracorporeal circulation • Great vessels

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