[Effects of dinitrosyl iron complex on metabolism and cellular membranes in ischemic rat heart]

Effects of exogenous NO donor--dinitrosyl iron complex with reduced glutathione (DNIC-GS) on functional recovery of isolated perfused rat heart subjected to global ischemia and reperfusion have been studied. DNIC-GS administration after ischemia substantially improved contractile and pump function recovery within a concentration range of 34 nM - 5 uM. In case of DNIC-GS administration before ischemia a two-phase influence was found--cardioprotective action for 67 nM and damaging one for 250 nM. Enhanced recovery of cardiac function after preischemic infusion of 67 nM DNIC-GS was associated with augmented preservation of ATP, phosphocreatine, total adenine nucleotide pool and total creatine content in myocardial tissue, and with reduction of lactate dehydrogenase (LDH) release into myocardial effluent compared with these indices in control. In contrast, infusion of 250 nM DNIC-GS resulted in poor recovery of energy metabolism and increased membrane injury than in control. The results suggest that a worse recovery of myocardial energy state and increased sarcolemma permeability in the 250 nM DNIC-GS group were caused by inhibiting oxidation of glucose, the main energy substrate for isolated perfused heart. Molecular mechanisms of protective and injurious action of DNIC-GS on ischemic heart are discussed.