Myocardial adaptation during and after sustained, demand-induced ischemia - Observations in closed-chest, domestic swine

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 Row, 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 la) at approximate to 50 minutes after stress. Group la had ischemia assessed with Tc-99m-labeled EMS 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 Row 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 Row and oxygen consumption were reduced approximate to 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 Row and oxygen consumption consistent with myocardial hibernation.