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(Circulation. 1996;94:755-762.)
© 1996 American Heart Association, Inc.

Articles

Myocardial Adaptation During and After Sustained, Demand-Induced Ischemia

Observations in Closed-Chest, Domestic Swine

Mark Berman, MD; Alan J. Fischman, MD, PhD; James Southern, MD, PhD; Edward Carter, PhD; Francis Mirecki, MD; H. William Strauss, MD; Adrian Nunn, PhD; Henry Gewirtz, MD

the Department of Medicine, Division of Cardiology, Rhode Island Hospital and Brown University School of Medicine, Providence (M.B., F.M.); Bristol Myers Squibb Pharmaceutical Research Institute, New Brunswick, NJ (H.W.S., A.N.); and Departments of Radiology (Nuclear Medicine) (A.J.F., E.C.), Pathology (J.S.), and Medicine (Cardiac Unit) (H.G.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Henry Gewirtz, MD, Cardiac Unit/Vincent Burnham 3, Massachusetts General Hospital, Boston, MA 02114. E-mail gewirtz@petw7.mgh.harvard.edu.

Background We tested the hypotheses that prolonged, demand-induced myocardial ischemia plateaus and that on relief of stress, myocardial function remains depressed, with proportionate reductions in blood flow and oxygen consumption indicative of hibernation.

Methods and Results Closed-chest swine (n=20) were prepared with an 80% coronary stenosis. Hemodynamics, myocardial blood flow, oxygen, and lactate metabolism were measured in group 1 (n=9) (1) at baseline, (2) at 10 and 30 minutes of atrial pacing plus intravenous norepinephrine infusion, and (3) in 5 of 9 (group 1a) at 50 minutes after stress. Group 1a had ischemia assessed with ^99mTc-labeled BMS 181321. In group 2 (n=11), myocardial function was determined with radionuclide ventriculography (n=8), and myocardial necrosis was looked for with trichlorotetrazolium chloride staining (n=7), histology (n=10), and myocardial creatine kinase concentration (n=4). Baseline stenotic-zone endocardial blood flow was reduced versus the normal zone (0.94±0.33 versus 1.38±0.27 mL·min^-1·g^-1, mean±SD; P<.05), whereas epicardial flows were comparable (1.15±0.36 versus 1.16±0.26 mL·min^-1·g^-1). Stenotic-zone endocardial flow was unchanged versus baseline at 10 and 30 minutes of stress, whereas epicardial flow increased (1.62±0.53 mL·min^-1·g^-1 at 10 minutes and 1.44±0.51 mL·min^-1·g^-1 at 30 minutes, both P<.05). Myocardial oxygen consumption increased versus baseline (10.8±2.9 mL·min^-1·100 g^-1) at 10 and 30 minutes of stress (14.9±5.2 and 13.9±4.5 mL·min^-1·100 g^-1, both P<.05). After stress, stenotic-zone blood flow and oxygen consumption were reduced 30% (P<.01) versus baseline. In group 2, stenotic-zone contraction with stress declined versus baseline and remained depressed throughout recovery. Histological and biochemical evidence of myocardial necrosis was absent in group 2.

Conclusions Myocardial ischemia induced by a sustained increase in oxygen demand may not progress to necrosis but may instead plateau. After relief of stress, myocardial function remains depressed, with a proportionate reduction in blood flow and oxygen consumption consistent with myocardial hibernation.

Key Words: myocardium • metabolism • blood flow • ischemia

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