• Jianzhong An, Amadou K S Camara, Matthias L Riess, Samhita S Rhodes, Srinivasan G Varadarajan, and David F Stowe.
• Anesthesiology Research Laboratory, Department of Anesthesiology, Medical College of Wisconsin, and Veterans Affairs Medical Center, Milwaukee, Wisconsin 53226, USA.
• J. Cardiovasc. Pharmacol. 2005 Sep 1; 46 (3): 280-7.

AbstractWe examined if sevoflurane given before cold ischemia of intact hearts (anesthetic preconditioning, APC) affords additional protection by further improving mitochondrial energy balance and if this is abolished by a mitochondrial KATP blocker. NADH and FAD fluorescence was measured within the left ventricular wall of 5 groups of isolated guinea pig hearts: (1) hypothermia alone; (2) hypothermia+ischemia; (3) APC (4.1% sevoflurane)+cold ischemia; (4) 5-HD+cold ischemia, and (5) APC+5-HD+cold ischemia. Hearts were exposed to sevoflurane for 15 minutes followed by 15 minutes of washout at 37 degrees C before cooling, 2 hours of 27 degrees C ischemia, and 2 hours of 37 degrees C reperfusion. The KATP channel inhibitor 5-HD was perfused before and after sevoflurane. Ischemia caused a rapid increase in NADH and a decrease in FAD that waned over 2 hours. Warm reperfusion led to a decrease in NADH and an increase in FAD. APC attenuated the changes in NADH and FAD and further improved postischemic function and reduced infarct size. 5-HD blocked the cardioprotective effects of APC but not APC-induced alterations of NADH and FAD. Thus, APC improves redox balance and has additive cardioprotective effects with mild hypothermic ischemia. 5-HD blocks APC-induced cardioprotective effects but not improvements in mitochondrial bioenergetics. This suggests that mediation of protection by KATP channel opening during cold ischemia and reperfusion is downstream from the APC-induced improvement in redox state or that these changes in redox state are not attenuated by KATP channel antagonism.

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