ATP-sensitive potassium channel (KATP) openers directly protect ischemic myocardium, which may make them useful for treating patients undergoing
cardiopulmonary bypass, but whether high-
potassium-containing
cardioplegic solutions would inhibit their protective effects is not clear. We determined whether additional protection greater than that provided by
cardioplegia could be found for KATP openers. We studied the effect of 10 microM
cromakalim or
BMS-180448 pretreatment (10 min before
cardioplegia) on severity of
ischemia in isolated rat hearts given normothermic or cold St. Thomas'
cardioplegic solution (16 mM K+). After cardioplegic arrest, the hearts were subjected to 30-min (normothermic) or 150-min (hypothermic) global
ischemia, each followed by 30-min reperfusion. The
cardioplegic solutions significantly protected the hearts, as measured by increased time to onset of
contracture, enhanced recovery 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; this was accompanied by enhanced recovery of reperfusion contractile function and reduced cumulative LDH release. This additional protective effect of the K
ATP openers was abolished by
glyburide. Because administration of the K
ATP openers only with the
cardioplegic solution (1 min before global
ischemia) was not efficacious, >1-min pretreatment apparently is necessary. K
ATP openers provide additional protection to that afforded by cold or normothermic
potassium cardioplegia in rat heart, although the timing of treatment may be crucial.