Oxidative phosphorylation function of two mitochondrial preparations from heart: effects of ischaemia and cytochrome C

The effects ofmyocardial ischaemia on twomitochondrial preparations (polytron and nagarse) were evaluated, using three different substrates to localize the defect in the electron transport chain. Coronary artery ligation and normothermic ischaemic arrest (NICA) of the isolated working perfused rat heart were used as models of ischaemia. The results showed that, although the degree to which these two mitochondrial preparations were affected by ischaemia might differ, mitochondrial function was altered in a similar manner. After 20 min of NICA, the polytron mitochondria appeared to be more susceptible to injury than the nagarse fraction. However, coronary artery ligation for 55 min depressed the QO2 (State 3) values of polytron and nagarse mitochondria to the same extent. Moderate ischaemia (coronary artery ligation for 55 min or NICA for 20 min) depressed the oxidative phosphorylation function of both mitochondrial populations with glutamate as substrate only, indicating that the NADH-coenzyme Q region of the electron transport chain is most sensitive to ischaemic injury. As the period and severity of ischaemia increased, the rest of the electron transport chain and the phosphorylating capacity of the mitochondria became depressed. In moderate ischaemia, addition of exogenous cytochrome C caused a complete return to normal QO2 values of both mitochondrial preparations. However, in severe ischaemia (55 min NICA), although cytochrome C improved mitochondrial oxygen uptake, the values were still significantly lower than those of control hearts.