Mitochondrial gene expression and ventricular fibrillation in ischemic/reperfused nondiabetic and diabetic myocardium.

We investigated the mitochondrial gene expression related to cardiac function and ventricular fibrillation (VF) in ischemic/reperfused nondiabetic and diabetic myocardium. To identify potentially more specific gene responses we performed subtractive screening, Northern blotting, and reverse transcription-polymerase chain reaction (RT-PCR) of mitochondrial genes expressed after 30 min ischemia followed by 120 min reperfusion in isolated rat hearts that showed VF or did not show VF. Cytochrome oxidase B subunit III (COXBIII) and ATP synthase subunit 6, studied and selected out of 40 mitochondrial genes by subtractive screening, showed an expression after 30 min ischemia (no VF was recorded) in both nondiabetic and diabetic subjects. Upon reperfusion, the down-regulation of these genes was only observed in fibrillated hearts. Such a reduction in signal intensity was not seen in nonfibrillated myocardium. In additional studies, nondiabetic and diabetic hearts, without the ischemia/reperfusion protocol, were subjected to electrical fibrillation, and a significant reduction in COXBIII and ATPS6 mRNA signal intensity was observed indicating that VF contributes to the down-regulation of these genes. Cardiac function (heart rate, coronary flow, aortic flow, left ventricular developed pressure) showed no correlation between the up- and down-regulation of these mitochondrial genes in both nondiabetic and diabetic ischemic/reperfused myocardium. Our data suggest that COXBIII and ATPS6 may play a critical role in arrhythmogenesis, and the stimulation of COXBIII and ATPS6 mRNA expression may prevent the development of VF in both nondiabetic and diabetic ischemic/reperfused myocardium.