(Circulation. 1999;100:2380.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Profound Apoptosis-Mediated Regional Myocyte Loss and Compensatory Hypertrophy in Pigs With Hibernating Myocardium
From the Veterans Affairs Western New York Healthcare System and the Departments of Medicine, Anatomy, Physiology, and Biophysics at the State University of New York at Buffalo School of Medicine and Biomedical Sciences.
Correspondence to John M. Canty, Jr, MD, Biomedical Research Building, Room 347, University at Buffalo, 3435 Main St, Buffalo, NY 14214. E-mail canty{at}buffalo.edu
Background—Myocyte apoptosis is seen in ischemic heart disease, but whether it can occur after reversible ischemia or independent of necrosis and replacement fibrosis is unknown.
Methods and Results—Pigs were instrumented with a stenosis of the left anterior descending coronary artery to chronically reduce coronary flow reserve over a period of 3 months. At this time, there was viable dysfunctional myocardium having the physiological features of hibernating myocardium. Resting subendocardial perfusion was reduced to 0.65±0.08 (mean±SEM) mL · min-1 · g-1 in hibernating myocardium of instrumented pigs compared with 0.98±0.14 mL · min-1 · g-1 in myocardium of sham-operated pigs (P<0.05). There was a critical limitation in subendocardial flow during vasodilation to 0.78±0.20 mL · min-1 · g-1 in instrumented pigs versus 3.24±0.50 mL · min-1 · g-1 in sham-operated pigs (P<0.001). Histology revealed a regional reduction in myocyte nuclear density to 995±100 nuclei/mm2 in hibernating myocardium from the instrumented group versus 1534±65 nuclei/mm2 in myocardium from the sham-operated group (P<0.05), regional myocyte hypertrophy (myocyte volume per nucleus, 14 183±2594 in the instrumented group versus 9130±1301 µm3 in the sham group; P<0.05), and minimal increases in connective tissue (5.8±0.9% in the instrumented group versus 3.0±0.2% in the sham group, P<0.05). Necrosis was not identified, but apoptosis was increased from 30±9 myocytes per 106 myocyte nuclei in myocardium from the sham group to 220±77 myocytes per 106 myocyte nuclei in hibernating myocardium (P<0.05).
Conclusions—These findings indicate that reversible ischemia in an area of chronically reduced coronary flow reserve induces regional myocyte loss via an apoptotic mechanism. This may contribute to the progression of chronic coronary disease to heart failure and explain the lack of complete functional recovery after revascularization in hibernating myocardium.
Key Words: myocardium • apoptosis • ischemia • cardiomyopathy • hibernation
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