Hibernating Myocardium Retains Metabolic and Contractile Reserve Despite Regional Reductions in Flow, Function, and Oxygen Consumption at Rest

Abstract

Abstract-Hibernating myocardium, characterized by reductions in flow and function at rest, has limited contractile reserve in response to increases in external workload. We hypothesized that this attenuation of function reflects an adaptive downregulation that prevents the development of metabolic evidence of ischemia during stress. To test this hypothesis, pigs were chronically instrumented with a proximal left anterior descending artery stenosis for 3 months, resulting in severe anteroapical hypokinesis with reduced resting perfusion (0.78Ϯ0.05 versus 0.94Ϯ0.07 mL · min Ϫ1 · g Ϫ1 in remote, PϽ0.01; and 0.99Ϯ0.08 in controls, PϽ0.05). Open-chest studies confirmed resting dysfunction compared with normal controls (segment shortening 9.2Ϯ2.2% versus 23.5Ϯ1.1%, PϽ0.05). Resting myocardial oxygen consumption was reduced (63Ϯ3 versus 77Ϯ6 L · g Ϫ1 · min Ϫ1 in controls, PϽ0.05), yet lactate consumption was normal. Although subendocardial perfusion failed to increase during graded, intravenous epinephrine infusion (nϭ8), peak segment shortening (to 17.3Ϯ3.1%, PϽ0.05) and oxygen consumption (to 90Ϯ6 L · g Ϫ1 · min Ϫ1 , PϽ0.01) increased from the depressed resting levels. There was no lactate production in hibernating myocardium, and lactate uptake increased during stress (0.7Ϯ0.1 to 1.2Ϯ0.1 mol · g Ϫ1 · min Ϫ1 , PϽ0.05). The absence of metabolic evidence of ischemia was also confirmed during atrial pacing to a rate of 120 bpm (nϭ8). Thus, despite reductions in function and oxygen consumption at rest, hibernating myocardium retains the ability to increase metabolism without the development of acute ischemia. This supports the hypothesis that the downregulation of oxygen consumption and function in hibernating myocardium is an adaptive response that prevents a supply-demand imbalance during submaximal increases in cardiac workload when coronary flow reserve is limited. Key Words: hibernating myocardium Ⅲ oxygen consumption Ⅲ lactate Ⅲ contractile reserve Ⅲ ␤-adrenergic stimulation H ibernating myocardium is characterized by chronic reductions in flow and function that occur in the absence of infarction or subjective evidence of acute ischemia. 1 Although flow is reduced at rest, the myocardium retains the ability to at least transiently respond to increases in external workload. While considerable attention has focused on assessing contractile reserve in hibernating myocardium, the metabolic responses at rest and during increases in the external determinants of myocardial oxygen consumption are largely unknown. In normal hearts, acute transient ischemia causes dysfunction that is accompanied by a rapid fall in high-energy phosphate levels and a switch to anaerobic glycolysis as evidenced by regional lactate production. When moderate ischemia is maintained for hours, however, reductions in regional function match the reduced levels of oxygen delivery. This prevents irreversible injury by reestablishing a balance between supply and demand, a phenomenon termed "short-term hibernation." 2 Although this reverses lactate rel...

Impaired resting perfusion in viable myocardium distal to chronic coronary stenosis in rats

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Long-term preservation of myocardial energetic in chronic hibernating myocardium

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