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Am J Physiol Heart Circ Physiol 282: H1961-H1969, 2002. First published February 14, 2002; doi:10.1152/ajpheart.01032.2001
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Vol. 282, Issue 6, H1961-H1969, June 2002

Cardiac preconditioning with 4-h, 17°C ischemia reduces [Ca2+]i load and damage in part via KATP channel opening

Qun Chen1,5, Amadou K. S. Camara1, Jianzhong An1, Matthias L. Riess1,2, Enis Novalija1,2, and David F. Stowe1,2,3,4

Anesthesiology Research Laboratories, Departments of 1 Anesthesiology and 2 Physiology, and 3 Cardiovascular Research Center, The Medical College of Wisconsin, Milwaukee, 53226; 4 Research Service, Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295; and 5 Xuzhou Medical College, Xuzhou, People's Republic of China 221002

Brief ischemia before normothermic ischemia protects hearts against reperfusion injury (ischemic preconditioning, IPC), but it is unclear whether it protects against long-term moderate hypothermic ischemia. We explored in isolated guinea pig hearts 1) the influence of two 2-min periods of normothermic ischemia before 4 h, 17°C hypothermic ischemia on cardiac cytosolic [Ca2+], mechanical and metabolic function, and infarct size, and 2) the potential role of KATP channels in eliciting cardioprotection. We found that IPC before 4 h moderate hypothermia improved myocardial perfusion, contractility, and relaxation during normothermic reperfusion. Protection was associated with markedly reduced diastolic [Ca2+] loading throughout both hypothermic storage and reperfusion. Global infarct size was markedly reduced from 36 ± 2 (SE)% to 15 ± 1% with IPC. Bracketing ischemic pulses with 200 µM 5-hydroxydecanoic acid or 10 µM glibenclamide increased infarct size to 28 ± 3% and 26 ± 4%, respectively. These results suggest that brief ischemia before long-term hypothermic storage adds to the cardioprotective effects of hypothermia and that this is associated with decreased cytosolic [Ca2+] loading and enhanced ATP-sensitive K channel opening.

cold storage; 5-hydroxydecanoic acid; glibenclamide; isolated hearts; guinea pig


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