Ischemic Preconditioning, mitoKATP Channel and In Vivo Myocardial Oxygen Consumption

Ischemic preconditioning (IPC) protects the postischemic heart. We determine this protection is due to opening of mitoK ATP channel and thereby decreased formation of ROS/RNS after reperfusion. Four groups of mice: control (I/R, mouse heart subjected to 30 min ischemia followed by 60 min reperfusion), preconditioned (IPC+I/R, 3 cycles of 5 min coronary occlusion/5 min R), diazoxide and 5‐hydroxydecanoate (5‐HD) treated (DIZ+I/R, 5‐HD+IPC+I/R), N=7. In vivo myocardial PO 2 was monitored by electron paramagnetic resonance oximetry. No difference was found in PO 2 at baseline and during 30 min I among all the groups. Myocardial PO 2 at 60 min R increased significantly above the preischemic value in I/R but not in IPC+I/R. With treatment of diazoxide, there was no overshoot of PO 2 , but when treated with 5‐HD, the overshoot of PO 2 re‐appeared in the preconditioned group. After 60 min R, activities of cytochrome c oxidase (CcO) and NADH dehydrogenase (NADH‐DH) were reduced in I/R and 5‐HD+IPC+I/R but conserved in IPC+I/R and DIZ+I/R. Nitrotyrosine formation was observed in I/R and 5‐HD+IPC+I/R but undetectable in IPC+I/R and DIZ+I/R after 60 min R. Thus in vivo, IPC markedly attenuated ROS/RNS generation possibly through the opening of mitoK ATP channel, up‐regulated O 2 consumption, and conferred protection in the postischemic heart with preserved mitochondrial O 2 metabolism due to conserved CcO and NADH‐DH activities.