Myocardial Adaptation During and After Sustained, Demand-Induced Ischemia

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.