Effect of graded reductions of coronary pressure and flow on myocardial metabolism and performance: a model of "hibernating" myocardium

Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.

The term "hibernating" myocardium has been applied to chronic left ventricular dysfunction without angina or ischemic electrocardiographic changes in patients with coronary artery disease that is reversed by therapy that increases myocardial blood flow. To investigate the relation between coronary blood flow and ventricular function experimentally, graded reductions in coronary artery pressure were produced in isolated perfused rat hearts as contractile performance (peak systolic pressure and its first derivative [dP/dt]) and metabolic variables were measured using phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy. As coronary pressure and flow were reduced, significant reductions in myocardial oxygen consumption and contractile performance were observed, which returned to control levels when coronary artery pressure and flow were restored to baseline values. Two phases of metabolic abnormality were observed. With modest reductions in coronary perfusion, proportionate reductions in myocardial oxygen consumption and contractile behavior were accompanied by a slight reduction in creatine phosphate but no significant lactate production. With greater reductions in coronary artery pressure and flow, creatine phosphate decreased more, adenosine triphosphate levels and myocardial pH decreased significantly and myocardial lactate production increased. The balanced reductions in myocardial contractility and oxygen consumption without metabolic abnormalities traditionally associated with "ischemia" observed in the first phase provides evidence in normal hearts for resetting of the myocardial contractile behavior and oxygen consumption in the presence of reduced coronary flow (that is, hibernating myocardium). The data suggest that reductions in adenosine diphosphate and the index of the reduced form of nicotinamide adenine dinucleotide (NADH) (lactate formation) do not explain the coupling between coronary artery pressure and flow and myocardial oxygen consumption as contractile performance decreases.

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