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Chronic nonocclusive coronary artery constriction impairs ventricular function, myocardial structure, and cardiac
J M Capasso1, A Malhotra, P Li
1Department of Medicine, New York Medical College, Valhalla 10595.
Insights
Chronic coronary artery constriction in rats leads to progressive heart dysfunction, myocyte loss, and fibrosis. Enzyme activity changes in contractile proteins correlate with the severity of cardiac damage, from dysfunction to failure.
Area of Science:
- Cardiovascular Physiology
- Cardiac Pathology
- Biochemistry
Background:
- Chronic nonocclusive coronary constriction is a model for studying heart disease.
- Understanding its effects on cardiac function and structure is crucial for developing treatments.
Purpose of the Study:
- To investigate the impact of chronic coronary constriction on cardiac hemodynamics, structural integrity, and contractile protein enzyme activity.
- To correlate these changes with the development of cardiac dysfunction and failure.
Main Methods:
- Coronary artery stenosis was induced in rats.
- Cardiac hemodynamics, tissue damage, and myofibrillar Mg(2+)- and Ca(2+)-ATPase activities were measured after 1 month.
- Rats were categorized into groups based on the severity of cardiac dysfunction.
Main Results:
- Coronary constriction led to moderate dysfunction, severe dysfunction, and heart failure.
- Histological analysis revealed myocytolytic necrosis and replacement fibrosis.
- Myofibrillar Mg(2+)-ATPase activity initially increased then decreased, while Ca(2+)-ATPase activity was reduced in severe dysfunction and failure.
Conclusions:
- A modest reduction in coronary artery diameter can cause progressive heart damage, including myocyte loss and fibrosis.
- Altered contractile protein enzyme activity contributes to cardiac dysfunction and failure.
- This model provides insights into the mechanisms underlying heart disease progression.
Abstract:
To determine the effects of chronic nonocclusive coronary constriction on cardiac hemodynamics, structural integrity, and contractile protein enzyme activity, the left coronary artery was narrowed in rats, and measurements of ventricular performance, magnitude, and distribution of tissue damage and myofibrillar Mg2+ and Ca2+ myosin ATPase activities were evaluated 1 month later. In the presence of coronary artery stenosis averaging 58%, three levels of involvement of global cardiac performance were identified, and the rats were divided accordingly. In the first group, only left ventricular end-diastolic pressure (LVEDP) was increased; in the second group, LVEDP and left ventricular +dP/dt and/or -dP/dt were affected; and in the third group, LVEDP, left ventricular +dP/dt and -dP/dt, and right ventricular end-diastolic pressure were impaired. Thus, left ventricular moderate dysfunction, severe dysfunction, and failure occurred with coronary narrowing. On a structural basis, coronary constriction resulted in an ongoing process characterized by acute myocytolytic necrosis and foci of replacement fibrosis in different stages of healing. The number of these lesion profiles in the left ventricular myocardium increased 4.7-, 4.4-, and 8.3-fold in rats with moderate dysfunction, severe dysfunction, and failure, respectively. Biochemically, Mg(2+)-ATPase activity of myofibrils increased biventricularly when moderate dysfunction was present. However, this parameter decreased with the appearance of severe dysfunction, reaching control values in ventricular failure. Ca2+ myosin ATPase activity was reduced in the left ventricle of rats with severe dysfunction and failure, whereas it was elevated in the right ventricle of rats with severe dysfunction. In conclusion, a fixed lesion of the left main coronary artery with a modest reduction in vessel luminal diameter generates a conditioned state of the heart characterized by a continuous loss of myocytes and replacement scarring, which, in combination with alterations in contractile protein enzyme activity, may be responsible for a number of abnormalities in cardiac dynamics ranging from moderate dysfunction to pump failure.