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.


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 approximately 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 approximately 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.
Berman
M
M
Department of Medicine, Rhode Island Hospital, Providence, USA.
Fischman
A J
AJ
Southern
J
J
Carter
E
E
Mirecki
F
F
Strauss
H W
HW
Nunn
A
A
Gewirtz
H
H
D000818:Animals; D001794:Blood Pressure; D003326:Coronary Circulation; D003327:Coronary Disease; D003402:Creatine Kinase / Q000378:metabolism; D006321:Heart / Q000000981:diagnostic imaging / Q000502:physiology / Q000503:physiopathology*; D006339:Heart Rate; D006439:Hemodynamics; D007773:Lactates / Q000378:metabolism; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; D010101:Oxygen Consumption; D011877:Radionuclide Imaging; D013312:Stress, Physiological; D013552:Swine; D013997:Time Factors
D007773:Lactates; D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; C082027:BMS 181321; D003402:Creatine Kinase