METABOLIC ADAPTATION DURING A SEQUENCE OF NO-FLOW AND LOW-FLOW ISCHEMIA - A POSSIBLE TRIGGER FOR HIBERNATION

Background Myocardial hibernation is an adaptive phenomenon occurring in patients with a history of acute ischemia followed by prolonged hyp operfusion. Methods and Results We investigated, in isolated rabbit he art, whether a brief episode of global ischemia followed by hypoperfus ion maintains viability. Four groups were studied: group 1, 300 minute s of aerobia; group 2, 240 minutes of total ischemia and 60 minutes of reperfusion; group 3, 10 minutes of total ischemia, 230 minutes of hy poperfusion (90% coronary flow reduction), and 60 minutes of reperfusi on; 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 mu mol/g dry wt, P<.01). Subsequent hypoperfusi on 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 p hosphokinase with no alterations of mitochondrial function or oxidativ e 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 mai ntains viability despite prolonged hypoperfusion. This could be mediat ed by metabolic adaptation, preconditioning, or both.