Protective effect of ischemia and diazoxide preconditioning on postischemic reperfused myocardium and possible mechanism thereof

Abstract

To study the protective mechanism of ischemic preconditioning (IPC) and diazoxide preconditioning (DPC) against myocardium ischemia-reperfusion (I/R) injury. The hearts were taken out from 30 male Wistar rats and were divided randomly into 3 equal groups: I/R group undergoing 30-min equilibration perfusion and 30-min ischemia and then 60-min reperfusion, IPC group undergoing 10-min equilibration perfusion and then two cycles of 5 min ischemia interspersed with 5 min reperfusion prior to 30 min ischemia and a 60-min reperfusion, and DPC group undergoing 10-min equilibration perfusion and 2 cycles of 5 min of 100 microM diazoxide perfusion followed by 5-min drug-free period before the 30 min ischemia and 60-min reperfusion. Frozen sections of myocardium at the cardiac apex were made and immunohistochemical staining was used to detect the expression of peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha). Ultrathin sections 70 nm thick were made and transmission electron microscopy was used to detect the structure of the mitochondria with the Flameng scoring system. The PGC-1alpha expression of the IPC and DPC groups were significantly higher than that of the I/R group (P<0.01 and P<0.05), however, there was no significant difference in PGC-1alpha is expression between the IPC and DPC groups (P >0.05). The Flameng scores of the IPC and DPC groups were 0.44 +/- 0.13 and 0.47 +/- 0.10 respectively, both significantly higher than that of the I/R group (1.78 +/- 0.14, both P <0.01), however, there was no significant difference between IPC and DPC groups (P>0.05). IPC and DPC can protect myocyte mitochondria from the injury of ischemia/ reperfusion. The cardioprotective effects of IPC and DPC may be concerned with the activation and high expression of PGC-1alpha.