PROTECTIVE EFFECT OF K-ATP OPENERS IN ISCHEMIC RAT HEARTS TREATED WITH A POTASSIUM CARDIOPLEGIC SOLUTION

ATP-sensitive potassium channel (K-ATP) openers directly protect ische mic myocardium, which may make them useful for treating patients under going cardiopulmonary bypass, but whether high-potassium-containing ca rdioplegic solutions would inhibit their protective effects is not cle ar. We determined whether additional protection greater than that prov ided by cardioplegia could be found for K-ATP openers. We studied the effect of 10 mu M cromakalim or BMS-180448 pretreatment (10 min before cardioplegia) on severity of ischemia in isolated rat hearts given no rmothermic or cold St. Thomas' cardioplegic solution (16 mM K+). After cardioplegic arrest, the hearts were subjected to 30-min (normothermi c) or 150-min (hypothermic) global ischemia, each followed by 30-min r eperfusion. The cardioplegic solutions significantly protected the hea rts, as measured by increased time to onset of contracture, enhanced r ecovery of function, and reduced lactate dehydrogenase (LDH) release. Cromakalim and BMS-180448 both further significantly increased time to contracture in both normothermic and hypothermic arrested hearts; thi s was accompanied by enhanced recovery of reperfusion contractile func tion and reduced cumulative LDH release. This additional protective ef fect of the K-ATP openers was abolished by glyburide. Because administ ration of the K-ATP openers only with the cardioplegic solution (1 min before global ischemia) was not efficacious, >1-min pretreatment appa rently is necessary. K-ATP openers provide additional protection to th at afforded by cold or normothermic potassium cardioplegia in rat hear t, although the timing of treatment may be crucial.