Glibenclamide improves postischemic recovery of myocardial contractile function in trained and sedentary rats

In this study, we sought to determine whether there was any evidence for th e idea that cardiac ATP-sensitive K+ (K-ATP) channels play a role in the tr aining-induced increase in the resistance of the heart to ischemia-reperfus ion (I/R) injury. To do so, the effects of training and an K-ATP channel bl ocker, glibenclamide (Glib), on the recovery of left ventricular (LV) contr actile function after 45 min of ischemia and 45 min of reperfusion were exa mined. Female Sprague-Dawley rats were sedentary (Sed; n = 18) or were trai ned (Tr; n = 17) for >20 wk by treadmill running, and the hearts from these animals used in a Langendorff-perfused isovolumic LV preparation to assess contractile function. A significant increase in the amount of 72-kDa class of heat shock protein was observed in hearts isolated from Tr rats. The I/ R protocol elicited significant and substantial decrements in LV developed pressure (LVDP), minimum pressure (MP), rate of pressure development, and r ate of pressure decline and elevations in myocardial Ca2+ content in both S ed and Tr hearts. In addition, I/R elicited a significant increase in LV di astolic stiffness in Sed, but not Tr, hearts. When administered in the perf usate, Glib (1 muM) elicited a normalization of all indexes of LV contracti le function and reductions in myocardial Ca2+ content in both Sed and Tr he arts. Training increased the functional sensitivity of the heart to Glib be cause LVDP and MP values normalized more quickly with Glib treatment in the Tr than the Sed group. The increased sensitivity of Tr hearts to Glib is a novel finding that may implicate a role for cardiac K-ATP channels in the training-induced protection of the heart from I/R injury.