Related Experiment Videos
Long-term coronary stenosis in rats: cardiac performance, myocardial morphology, and contractile protein enzyme
P Anversa1, A Malhotra, X Zhang
1Department of Medicine, New York Medical College, Valhalla 10595.
Insights
Chronic coronary artery stenosis in rats impairs cardiac function and causes fibrosis. Myocardial damage, not enzyme activity, drives long-term ventricular dysfunction and failure.
Area of Science:
- Cardiovascular Physiology
- Cardiac Pathology
- Biochemistry
Background:
- Chronic nonocclusive coronary constriction is a model for studying heart disease.
- Understanding the long-term effects on cardiac function and structure is crucial.
Purpose of the Study:
- To investigate the impact of chronic coronary constriction on cardiac hemodynamics.
- To analyze myocardial structural changes and contractile protein enzyme activity.
- To correlate these changes with ventricular dysfunction and failure.
Main Methods:
- Rats underwent left coronary artery narrowing (stenosis ~56%).
- Cardiac hemodynamics, ventricular function (dP/dt), and tissue damage were assessed 3 months post-procedure.
- Myofibrillar Mg2+ and Ca2+ myosin adenosinetriphosphatase (ATPase) activities and myosin isoenzymes were measured.
Main Results:
- Two groups showed depressed cardiac performance; one with increased left ventricular end-diastolic pressure (LVEDP) and decreased dP/dt, the other with more widespread ventricular impairment.
- Failing hearts exhibited significantly more replacement fibrosis than those with dysfunction.
- No significant changes in Mg2+-ATPase or Ca2+ myosin ATPase activity were observed; however, a shift in myosin isoenzymes (V1 to V3) occurred in failing left ventricles.
Conclusions:
- Chronic coronary stenosis leads to left ventricular dysfunction and failure.
- The extent of myocardial damage is a primary determinant of late impairment in ventricular pump function.
- Contractile protein enzyme activity alterations are less critical than structural damage in sustained dysfunction.
Abstract:
To determine the effects of chronic nonocclusive coronary constriction on cardiac hemodynamics, myocardial structure, and contractile protein enzyme activity, the left coronary artery was narrowed in rats, and measurements of ventricular pump function, extent and localization of tissue damage, and myofibrillar Mg2+ and Ca2+ myosin adenosinetriphosphatase (ATPase) activities were measured 3 mo later. In the presence of coronary artery stenosis averaging 56%, two different degrees of depression in global cardiac performance were identified, and the animals were divided in two groups. In the first group, left ventricular end-diastolic pressure (LVEDP) was increased and LV+ and/or--the first derivative of LV pressure (dP/dt) were decreased, whereas in the second group end-diastolic and peak systolic LV pressures, LV+ and -dP/dt and right ventricular dynamics were all impaired. Thus left ventricular dysfunction and failure occurred with coronary narrowing. Structurally, multiple foci of replacement fibrosis were found across the left ventricular wall, but the number of these lesion profiles was 2.6-fold larger in failing animals than in rats with cardiac dysfunction. Biochemically, Mg(2+)-ATPase activity in myofibrils and Ca2+ myosin ATPase were not altered biventricularly. On the other hand, a shift from V1 to V3 myosin isoenzymic content occurred in the failing left ventricle. In conclusion, the late impairment in ventricular pump function associated with prolonged coronary artery stenosis appears to be sustained more by the magnitude of myocardial damage than by defects in contractile protein enzyme activity.