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 me chanisms involved are yet to be elucidated. Opening of ATP-sensitive p otassium (K-ATP) channels has been demonstrated to be involved in othe r endogenous forms of cardioprotection, in particular ''classic'' isch emic preconditioning and delayed preconditioning following treatment w ith the endotoxin derivative, monophosphoryl lipid A. We therefore spe culated that there may be a role for K-ATP channels in delayed heat st ress-induced cardioprotection. This hypothesis was investigated in an in vivo rabbit model of acute myocardial infarction using two structur ally dissimilar K-ATP channel blockers, glibenclamide and sodium 5-hyd roxydecanoate. Sodium pentobarbitone-anesthetized rabbits were subject ed to either transient heat stress at 42 +/- 0.2 degrees C for 15 minu tes or sham anesthesia. Twenty-four hours later, animals were reanesth etized (''Hypnorm'' and sodium pentobarbitone) and a midline sternotom y and pericardiotomy were performed. An anterolateral branch of the ci rcumflex coronary artery was occluded for 30 minutes and reperfused fo r 2 hours. The infarct-to-risk ratio was significantly limited in vehi cle-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 glibenc lamide or 5 mg/kg iv 5-hydroxydecanoate when administered 10 minutes p rior to coronary occlusion (45.2 +/- 6.4%; n = 9 and 41.5 +/- 5.0%; n = 5, respectively.) The same doses of glibenclamide and 5-hydroxydecan oate 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 stre ss protocol was confirmed by Western blot analysis of the inducible 72 -kD heat stress protein. It is concluded, therefore, that K-ATP channe ls appear to play a role in the heat stress response. The underlying m echanisms involved are, however, unclear.