Effect of α-lipoic acid and dihydrolipoic acid on ischemia/reperfusion injury of the heart and heart mitochondria

AbstractThe aim of the present study was to evaluate a possible interference of a-lipoic acid (LA) or its reduced form (dithiol dihydrolipoic acid = DHLA) in the cardiac ischemia/reperfusion injury both at the level of the intact organ and at the subcellular level of mitochondria. In order to follow the effect of LA on the ischemia/reperfusion injury of the heart the isolated perfused organ was subjected to total global ischemia and reperfusion in the presence and absence of different concentrations of LA. Treatment with 0.5 μM LA improved the recovery of hemodynamic parameters; electrophysiological parameters were not influenced. However, application of 10 μM LA to rat hearts further impaired the recovery of hemodynamic functions and prolonged the duration of severe rhythm disturbances in comparison to reperfusion of control hearts. Treatment of isolated mitochondria with any concentration of DHLA could not prevent the impairment of respiratory-linked energy conservation caused by the exposure of mitochondria to `reperfusion' conditions. However, DHLA was effective in decreasing the formation and the existence of mitochondria) superoxide radicals (O2−) Apart from :ts direct 02-scavenging activities DHLA was also found to control mitochondria) O2− formation indirectly by regulating redox-cycling ubiquinone. It is suggested that impairment of this mitochondria) O2− generator mitigates postischemic oxidative stress which in turn reduces damage to hemodynamic heart function