Myocardial ischemic tolerance following heat stress is abolished by ATP-sensitive potassium channel blockade

Heat stress is known to confer protection against ischemia, but the mechanisms involved are yet to be elucidated. Opening of ATP-sensitive potassium (K-ATP) channels has been demonstrated to be involved in other endogenous forms of cardioprotection, in particular "classic" ischemic preconditioning and delayed preconditioning following treatment with the endotoxin derivative, monophosphoryl lipid A. We therefore speculated that there may be a role for K-ATP channels in delayed heat stress-induced cardioprotection. This hypothesis was investigated in an in vivo rabbit model of acute myocardial infarction using two structurally dissimilar K-ATP channel blockers, glibenclamide and sodium 5-hydroxydecanoate. Sodium pentobarbitone-anesthetized rabbits were subjected to either transient heat stress at 42 +/- 0.2 degrees C for 15 minutes or sham anesthesia. Twenty-four hours later, animals were reanesthetized ("Hypnorm" and sodium pentobarbitone) and a midline sternotomy and pericardiotomy were performed. An anterolateral branch of the circumflex coronary artery was occluded for 30 minutes and reperfused for 2 hours. The infarct-to-risk ratio was significantly limited in vehicle-treated rabbits from 41.3 +/- 4.0% in controls (n = 10) to 24.1 +/- 5.0% (n = 9; P = 0.014 by one-factor ANOVA) in heat-stressed hearts. This limitation in infarct size was abolished by 0.3 mg/kg iv glibenclamide or 5 mg/kg iv 5-hydroxydecanoate when administered 10 minutes prior to coronary occlusion (45.2 +/- 6.4%; n = 9 and 41.5 +/- 5.0%; n = 5, respectively.) The same doses of glibenclamide and 5-hydroxydecanoate in sham-anesthetized hearts had no effect (42.8 +/- 5.1%; n = 10 and 51.9 +/- 2.2%; n = 6, respectively). The adequacy of the heat stress protocol was confirmed by Western blot analysis of the inducible 72-kD heat stress protein. It is concluded, therefore, that K-ATP channels appear to play a role in the heat stress response. The underlying mechanisms involved are, however, unclear.