Cardioprotection induced by ischemic preconditioning in the mammalian heart: effects on arrhythmogenesis

Ischemic preconditioning (PC) describes the protection that occurs when a brief period of ischemia increases the tolerance of the heart to a future ischemic episode of longer duration. This protection is typically measured as a reduction in myocardial infarct size or improved recovery of contractile function. Few studies have tested whether PC also prevents the occurrence of severe arrhythmias, such as ventricular tachycardia (VT) and fibrillation (VF). We studied the effects of preconditioning on arrhythmias in Langendorff-perfused rabbit hearts. All hearts were subjected to a 30-min test ischemia followed by reperfusion. Preconditioned hearts underwent one to four ischemic periods (5 min each, separated by 10 min of reperfusion) 30 min prior to the test ischemia. VF occurred in 42% of non-PC hearts during ischemia. One PC period totally suppressed VF (0%; p < 0.05) and two PC periods provided partial protection (VF = 17%). In contrast, 64 and 50% of hearts receiving three or four PC periods fibrillated during ischemia, respectively. The test ischemia induced an ischemic contracture that was prevented by two or three PC periods, but not one or four PC periods. None of the PC protocols improved postischemic contractile recovery. In conclusion, our data show that a single PC period completely protects against ischemia-induced VF in rabbit hearts. Preconditioning also prevents development of an ischemic contracture. However, the optimal preconditioning "dose" that prevents arrhythmias is not the same as that which protects against contractile dysfunction.