Phosphorylation and redox states in ischemic liver

Abstract

Metabolite concentrations, redox and phosphorylation states were studied in ischemic and postischemic rat livers; oxidative phosphorylation and related functional parameters also were investigated with mitochondria derived from these tissues. Time periods were chosen to assess the effects of short-duration (15 min), long-duration reversible (60 min), and necrogenic ischemia (120 min). The energy-charge of liver cells drops promptly and deeply within the first 15 min of ischemia, with a concurrent profound decrease of the [NAD +] [NADH] ratio both in cytoplasm and mitochondria. Once affected by this initial change, redox and phosphorylation states do not vary appreciably by prolonging blood deprivation for 120 min. The functional capacity of isolated mitochondria declines steadily with increasing duration of ischemia and severe reductions—especially of the ADP O ratios—are attained only at the end of 120 min of ischemia. The reestablishment of the blood supply promotes a good recovery of the energy-charge and redox states (at a slightly different pace) only if previous ischemia did not last more than 60 min. Results with isolated mitochondria correlate well with chemical determinations carried out on postischemic tissue, but respiratory control index does not recover completely over the investigated period following reversible ischemia, thus indicating a less tight coupling of phosphorylation to oxidation during the repair of reversible cellular damage. The relationships between impaired mitochondrial functions, phosphorylation and redox states, and the relevance of their changes to the fate of ischemic cells are discussed.