EFFECT OF PROLONGED HYPOTHERMIC ISCHEMIA AND REPERFUSION ON OXYGEN-CONSUMPTION AND TOTAL MECHANICAL ENERGY IN RAT MYOCARDIUM - PARTICIPATION OF MITOCHONDRIAL OXIDATIVE PHOSPHORYLATION

Background. To reduce ischemia-reperfusion injury of hearts in open he art surgery and transplantation, it is important to know the critical period of ischemia in which donor hearts can sustain their function sa tisfactorily. Cardiac function has been deduced from oxygen consumptio n (VO2) and mechanical parameters such as pressure-volume area (PVA). Inhibited mitochondrial oxidative phosphorylation during ischemia indi cates that ATP production is uncoupled from VO2. Therefore, both mitoc hondrial oxidative phosphorylation and total mechanical energy should be examined to evaluate cardiac function after ischemia and reperfusio n. Methods. Isolated rat hearts were stored in Euro-Collins solution a t 4 degrees C for 8, 12, and 24 hr and reperfused in a working mode wi th a modified Krebs-Henseleit bicarbonate solution. PVA and VO2 were e xamined in isovolumic contraction, and ventricular contractility and t otal mechanical energy were assessed, respectively, by the end-systoli c elastance (Ees) and PVA. Mitochondrial oxidative phosphorylation in the presence of succinate and mitochondrial lipid peroxide levels were estimated in similarly treated rat hearts. Results. Ees was decreased by ischemia without significant difference. The VO2 to PVA ratio rema ined Linear, although VO2 at null PVA and the VO2 to PVA ratio signifi cantly increased after 12 hr of ischemia. Mitochondrial oxidative phos phorylation was decreased significantly by reperfusion after 12 hr of ischemia. Mitochondrial lipid peroxide levels were increased significa ntly after 12 hr of ischemia. Conclusions. In isolated rat hearts, dec reased efficiency for energy conversion from consumed oxygen to cardia c performance occurs between 8 and 12 hr of hypothermic ischemia, whic h was coincident with disturbed mitochondrial oxidative phosphorylatio n, to which lipid peroxidation may contribute.