Metabolic Adaptation During a Sequence of No-Flow and Low-Flow Ischemia

Abstract

Background Myocardial hibernation is an adaptive phenomenon occurring in patients with a history of acute ischemia followed by prolonged hypoperfusion. Methods and Results We investigated, in isolated rabbit heart, whether a brief episode of global ischemia followed by hypoperfusion maintains viability. Four groups were studied: group 1, 300 minutes of aerobia; group 2, 240 minutes of total ischemia and 60 minutes of reperfusion; group 3, 10 minutes of total ischemia, 230 minutes of hypoperfusion (90% coronary flow reduction), and 60 minutes of reperfusion; and group 4, 240 minutes of hypoperfusion followed by reperfusion. In group 3, viability was maintained. Ten minutes of ischemia caused quiescence, a fall in interstitial pH (from 7.2±0.01 to 6.1±0.8), creatine phosphate (CP), and ATP (from 54.5±5.0 and 25.0±1.9 to 5.0±1.1 and 15.3±2.5 μmol/g dry wt, P <.01). Subsequent hypoperfusion failed to restore contraction and pH but improved CP (from 5.0±1.1 to 20.1±3.4, P <.01). Reperfusion restored pH, developed pressure (to 92.3%), and NAD/NADH and caused a washout of lactate and creatine phosphokinase with no alterations of mitochondrial function or oxidative stress. In group 4, hypoperfusion resulted in progressive damage. pH fell to 6.2±0.7, diastolic pressure increased to 34±5.6 mm Hg, CP and ATP became depressed, and oxidative stress occurred. Reperfusion partially restored cardiac metabolism and function (47%). Conclusions A brief episode of total ischemia without intermittent reperfusion maintains viability despite prolonged hypoperfusion. This could be mediated by metabolic adaptation, preconditioning, or both.