EFFECT OF ALPHA-LIPOIC ACID AND DIHYDROLIPOIC ACID ON ISCHEMIA-REPERFUSION INJURY OF THE HEART AND HEART-MITOCHONDRIA

The aim of the present study was to evaluate a possible interference o f or-lipoic acid (LA) or its reduced form (dithiol dihydrolipoic acid = DHLA) in the cardiac ischemia/reperfusion injury both at the level o f the intact organ and at the subcellular level of mitochondria. In or der to follow the effect of LA on the ischemia/reperfusion injury of t he heart the isolated perfused organ was subjected to total global isc hemia and reperfusion in the presence and absence of different concent rations of LA, Treatment with 0.5 mu M LA improved the recovery of hem odynamic parameters; electrophysiological parameters were not influenc ed. However, application of 10 mu M LA to rat hearts further impaired the recovery of hemodynamic functions and prolonged the duration of se vere rhythm disturbances in comparison to reperfusion of control heart s. Treatment of isolated mitochondria with any concentration of DHLA c ould not prevent the impairment of respiratory-linked energy conservat ion caused by the exposure of mitochondria to 'reperfusion' conditions . However, DHLA was effective in decreasing the formation and the exis tence of mitochondrial superoxide radicals (O-2(-)). Apart from its di rect O-2(-)-scavenging activities DHLA was also found to control mitoc hondrial O-2(-) formation indirectly by regulating redox-cycling ubiqu inone. It is suggested that impairment of this mitochondrial O-2(-) ge nerator mitigates postischemic oxidative stress which in turn reduces damage to hemodynamic heart function.