IMPROVED CONTRACTILITY AND CORONARY FLOW IN ISOLATED HEARTS AFTER 1-DAY HYPOTHERMIC PRESERVATION WITH ISOFLURANE IS NOT DEPENDENT ON K-ATP CHANNEL ACTIVATION

Background: Isoflurane protects against reperfusion injury in isolated hearts when given before, during, and initially after hypoxia or isch emia and aids in preconditioning hearts if given before ischemia, The aims of the current study were to determine if isoflurane is cardiopro tective during 1-day, severe hypothermic perfusion and if a mechanism of protection is K-ATP channel activation. Methods: Guinea pig hearts (n = 60) were isolated, perfused with Kreb's solution initially at 37 degrees C, and assigned to either a nontreated warm, time control grou p or one of five cold-treated groups: drug-free cold control, 1.3% iso flurane, 1.3% isoflurane plus glibenclamide (4 mu M), 2.6% isoflurane, or 2.6% isoflurane plus glibenclamide. Isoflurane and glibenclamide w ere given 20 min before hypothermia, during low-flow hypothermia (3.8 degrees C) for 22 h, and for 30 min after rewarming to 37 degrees C, H eart rate, left ventricular pressure, %O-2 extraction, and coronary fl ow were measured continuously, and responses to epinephrine, adenosine , 5-hydroxytryptamine, and nitroprusside were examined before and afte r hypothermia. Results: Each group had similar initial left ventricula r pressures, coronary flows, and responses to adenosine, 5-hydroxytryp tamine, and nitroprusside. Before hypothermia, isoflurane with or with out glibenclamide increased coronary now while decreasing left ventric ular pressure and %O-2 extraction. After hypothermia, left ventricular pressure and coronary flow were reduced in all cold groups but least reduced in isoflurane-treated groups, During normothermic perfusion af ter isoflurane and glibenclamide, left ventricular pressure, coronary flow, %O-2 extraction, and now responses to adenosine, 5-hydroxytrypta mine, and nitroprusside were similarly improved in isoflurane and isof lurane-plus-glibenclamide groups over the cold control group but not t o levels observed in the warm-time control group, Conclusion: Isoflura ne, like halothane, given before, during, and initially after hypother mia markedly improved but did not restore cardiac perfusion and functi on, Protective effects of isoflurane were not concentration dependent and not inhibited by the K-ATP channel blocker glibenclamide, Volatile anesthetics have novel cardioprotective effects when given during lon g-term severe hypothermia.