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Coronary constriction impairs cardiac function and induces myocardial damage and ventricular remodeling in mice
Abstract:
To establish whether coronary artery narrowing (CAN) in mice was accompanied by depressed ventricular function, tissue injury, and modifications in cardiac anatomy, the left coronary artery was constricted in FVB/N mice and the animals were killed 7 days later. CAN consisted of a 53% reduction in luminal diameter, which resulted in a twofold increase in left ventricular end-diastolic pressure. Left ventricular systolic pressure and left ventricular + and -dP/dt decreased 15, 21, and 11%, respectively. Left ventricular weight-to-body weight ratio increased 33%. This hypertrophic adaptation was characterized by a 9 and 20% increase in the longitudinal and transverse cavitary diameters, which provoked a 1.5-fold expansion in chamber volume. In contrast, wall thickness decreased 15%. These anatomic and functional changes induced a threefold elevation in diastolic stress. Foci of reparative fibrosis were found in the endomyocardium and epimyocardium, involving 2-3% of the tissue. Finally, myocyte loss in the ventricle was 15%, and myocyte hypertrophy was 38%. Impaired ventricular function, diastolic Laplace overloading, myocyte loss, and decompensated eccentric hypertrophy in mice after CAN mimic the ischemic cardiomyopathic heart in humans.
Insights
Coronary artery narrowing in mice caused impaired ventricular function, cardiac remodeling, and cell death, mimicking human ischemic cardiomyopathy. This study details the anatomical and functional changes following induced coronary artery narrowing.
Area of Science:
- Cardiovascular Biology
- Cardiac Pathophysiology
- Animal Models of Heart Disease
Background:
- Coronary artery narrowing (CAN) is a significant factor in human heart disease.
- Understanding the cardiac consequences of CAN in animal models is crucial for developing treatments.
Purpose of the Study:
- To investigate the effects of induced coronary artery narrowing on ventricular function, cardiac anatomy, and tissue integrity in mice.
- To establish a mouse model that mimics human ischemic cardiomyopathy.
Main Methods:
- Constriction of the left coronary artery in FVB/N mice.
- Assessment of cardiac anatomy, ventricular pressures, and contractility 7 days post-constriction.
- Histological analysis for fibrosis and myocyte changes.
Main Results:
- CAN led to a 53% reduction in luminal diameter, increased left ventricular end-diastolic pressure, and decreased systolic pressure and contractility.
- Significant cardiac remodeling occurred, including increased ventricular weight, chamber volume expansion, and decreased wall thickness, resulting in elevated diastolic stress.
- Histology revealed reparative fibrosis, 15% myocyte loss, and 38% myocyte hypertrophy.
Conclusions:
- Induced coronary artery narrowing in mice results in impaired ventricular function, significant cardiac remodeling, and myocyte alterations.
- The observed changes, including diastolic stress, myocyte loss, and eccentric hypertrophy, effectively model the human ischemic cardiomyopathic heart.
- This mouse model provides a valuable platform for studying the pathophysiology and potential therapeutic strategies for ischemic cardiomyopathy.