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Effects of captopril on contractility after myocardial infarction: experimental observations
S E Litwin1, T E Raya, A Warner
1Department of Internal Medicine, Tucson Veterans Administration Medical Center, Arizona 85723.
Insights
Angiotensin-converting enzyme inhibitors like captopril improve heart failure but show modest effects on cardiac muscle function. This study in rats reveals captopril impacts left ventricular remodeling but not fully restoring muscle performance.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Heart Failure Pathophysiology
Background:
- Chronic heart failure (CHF) follows myocardial infarction, impairing left ventricular (LV) function and peripheral circulation.
- Angiotensin-converting enzyme (ACE) inhibitors improve cardiovascular function, but their impact on organ vs. muscle function is unclear.
- A rat model of myocardial infarction mimics human CHF, exhibiting elevated LV end-diastolic pressure, hypertrophy, and impaired relaxation.
Purpose of the Study:
- To investigate the effects of captopril on cardiac muscle function in a rat model of heart failure.
- To differentiate the impact of ACE inhibition on LV remodeling versus direct muscle function.
Main Methods:
- Induction of heart failure in rats via left coronary artery ligation.
- Isolation of noninfarcted papillary muscles for functional assessment (developed tension, +dT/dt, stiffness).
- Administration of captopril and assessment of LV loading, hemodynamics, and myocardial morphology (myocyte size, collagen content).
Main Results:
- Captopril reduced LV loading (arterial pressure, LV end-diastolic pressure/volume) and improved venous compliance.
- In noninfarcted papillary muscles, captopril shortened time to peak tension but failed to normalize developed tension, +dT/dt, or stiffness.
- Captopril decreased myocyte cross-sectional area but did not reduce elevated myocardial collagen content.
Conclusions:
- Captopril treatment in this rat heart failure model effectively alters LV remodeling and reduces hypertrophy.
- Despite hemodynamic improvements, captopril demonstrates only modest beneficial effects on impaired cardiac muscle function.
- The study highlights a dissociation between ACE inhibitor effects on cardiac remodeling and direct myocardial contractility.
Abstract:
After large myocardial infarction, compromised left ventricular (LV) function and changes in the peripheral circulation result in the syndrome of chronic congestive heart failure. Although treatment with angiotensin-converting enzyme inhibitors improve cardiovascular function, it is difficult to determine whether this benefit is due to changes in organ versus muscle function. The rat model of heart failure, created by ligating the left coronary artery, results in pathophysiology that is similar to that seen in patients, i.e., increased LV end-diastolic pressure and volume, hypertrophy of the noninfarcted myocardium, prolongation of the time constant of LV relaxation, decreased venous compliance, and increased total blood volume. In noninfarcted papillary muscles, isolated from rats with heart failure, maximal developed tension and peak rate of tension rise (+dT/dt) are decreased, time to peak tension is prolonged, and myocardial stiffness is increased. Morphologic changes include an increase in papillary muscle myocyte cross-sectional area and an increase in myocardial hydroxyproline content. Captopril (2 g/liter drinking water) alters LV loading by decreasing arterial pressure, increasing venous compliance, and decreasing blood volume. This results in a decrease in LV end-diastolic pressure and volume. In the noninfarcted myocardium, time to peak tension is shortened, whereas developed tension, +dT/dt, and muscle stiffness remain abnormal. Captopril decreases myocyte cross-sectional area, but collagen content remains elevated. Thus, in the rat infarct model of heart failure, treatment with captopril alters LV remodeling and hypertrophy but produces only modest improvement in muscle function.(ABSTRACT TRUNCATED AT 250 WORDS)