(Circulation. 1996;94:2587-2596.)
© 1996 American Heart Association, Inc.
Articles |
Metabolic Adaptation During a Sequence of No-Flow and Low-Flow Ischemia
A Possible Trigger for Hibernation
the Chair of Cardiology (R.F., S.C., C.C.), University of Brescia, Brescia, Italy; Center of Cardiovascular Pathophysiology (A.C., P.B., E.P.), "S. Maugeri," Foundation, IRCCS, Rehabilitation Institute of Gussago, Brescia, Italy; and Heart Lung Institute (T.J.C.R.), University Hospital, Utrecht, and the InterUniversity Cardiology Institute, the Netherlands.
Correspondence to Prof Roberto Ferrari, Cattedra di Cardiologia, Spedali Civili, P.le Spedali Civili, 1, 25123 Brescia, Italy. E-mail ferrari@master.cci.unibs.it.
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.
Key Words: myocardial hibernation • ischemia • metabolism • preconditioning
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