Affiliation:
1. 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.
Abstract
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
99m
Tc-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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
24 articles.
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