Published online before print December 2, 2002, doi: 10.1161/01.RES.0000049104.57549.03
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Submitted on August 15, 2002
Revised on November 12, 2002
Accepted on November 12, 2002
Hibernating Myocardium Retains Metabolic and Contractile Reserve Despite Regional Reductions in Flow, Function, and Oxygen Consumption at Rest
James A. Fallavollita *;
From the VA Western New York Health Care System and the Departments of Medicine and Physiology & Biophysics at the University at Buffalo, NY.
* To whom correspondence should be addressed. E-mail: jaf7{at}buffalo.edu.
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 (0.78±0.05 versus 0.94+0.07 mL · min-1 · g-1 in remote, P<0.01; and 0.99±0.08 in controls, P<0.05). Open-chest studies confirmed resting dysfunction compared with normal controls (segment shortening 9.2±2.2% versus 23.5±1.1%, P<0.05). Resting myocardial oxygen consumption was reduced (63±3 versus 77±6 µL · g-1 · min-1 in controls, P<0.05), yet lactate consumption was normal. Although subendocardial perfusion failed to increase during graded, intravenous epinephrine infusion (n=8), peak segment shortening (to 17.3±3.1%, P<0.05) and oxygen consumption (to 90±6 µL · g-1 · min-1, P<0.01) increased from the depressed resting levels. There was no lactate production in hibernating myocardium, and lactate uptake increased during stress (0.7±0.1 to 1.2±0.1 µL · g-1 · min-1, P<0.05). The absence of metabolic evidence of ischemia was also confirmed during atrial pacing to a rate of 120 bpm (n=8). 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 • oxygen consumption • lactate • contractile reserve •
-adrenergic stimulation
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