K-ATP channel activation reduces the severity of postresuscitation myocardial dysfunction

Postresuscitation myocardial dysfunction has been recognized as a leading c ause of the high postresuscitation mortality rate. We investigated the effe cts 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 ini tiated after 4 min of untreated VF. Defibrillation was attempted after 6 mi n of CPR. The animals were randomized to five groups treated with 1) ischem ic preconditioning, 2) K-ATP channel opener, 3) ischemic preconditioning wi th K-ATP channel blocker administered 1 min after VF, 4) K-ATP channel bloc ker administered 45 min before induction of ischemic preconditioning, and 5 ) placebo. Postresuscitation myocardial function, as measured by the rate o f left ventricular pressure increase at 40 mmHg, the rate of left ventricul ar decline, cardiac index, and duration of survival, was significantly impr oved in both preconditioned and K-ATP channel opener-treated animals. K-ATP channel blocker administered 45 min before induction of ischemic precondit ioning completely abolished the myocardial protective effects of preconditi oning. We conclude that ischemic preconditioning significantly improved pos t-CPR myocardial function and survival. These results also provide evidence that the myocardial protective effects of ischemic preconditioning are med iated by K-ATP channel activation.