K(ATP) channel activation reduces the severity of postresuscitation myocardial dysfunction.

Postresuscitation myocardial dysfunction has been recognized as a leading cause of the high postresuscitation mortality rate. We investigated the effects of ischemic preconditioning and activation of ATP-sensitive K(+) (K(ATP)) channels on postresuscitation myocardial function. Ventricular fibrillation (VF) was induced in 25 Sprague-Dawley rats. Cardiopulmonary resuscitation (CPR), including mechanical ventilation and precordial compression, was initiated after 4 min of untreated VF. Defibrillation was attempted after 6 min of CPR. The animals were randomized to five groups treated with 1) ischemic preconditioning, 2) K(ATP) channel opener, 3) ischemic preconditioning with K(ATP) channel blocker administered 1 min after VF, 4) K(ATP) channel blocker administered 45 min before induction of ischemic preconditioning, and 5) placebo. Postresuscitation myocardial function, as measured by the rate of left ventricular pressure increase at 40 mmHg, the rate of left ventricular decline, cardiac index, and duration of survival, was significantly improved in both preconditioned and K(ATP) channel opener-treated animals. K(ATP) channel blocker administered 45 min before induction of ischemic preconditioning completely abolished the myocardial protective effects of preconditioning. We conclude that ischemic preconditioning significantly improved post-CPR myocardial function and survival. These results also provide evidence that the myocardial protective effects of ischemic preconditioning are mediated by K(ATP) channel activation.