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Angiotensin I converting enzyme inhibitors and cardiac remodeling
C van Krimpen1, R G Schoemaker, J P Cleutjens
1Department of Pathology, University of Limburg, Maastricht, The Netherlands.
Insights
Early Angiotensin I converting enzyme (ACE) inhibitor treatment after myocardial infarction hinders beneficial cardiac remodeling. Late treatment showed no effects, suggesting ACE inhibitors may interfere with adaptive cellular responses.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Cardiac Physiology
Background:
- Angiotensin I converting enzyme (ACE) inhibitors are standard treatments for heart failure.
- The precise mechanisms behind ACE inhibitors' benefits, particularly regarding cardiac remodeling post-myocardial infarction, remain unclear.
- The impact of treatment timing on these effects is also not well-established.
Purpose of the Study:
- To investigate the effects of early versus late Angiotensin I converting enzyme (ACE) inhibitor treatment on cardiac remodeling after myocardial infarction.
- To determine if ACE inhibition has direct effects on cardiac structural changes beyond preload and afterload reduction.
- To explore the role of treatment timing in mediating ACE inhibitor effects on the post-infarction heart.
Main Methods:
- Myocardial infarction was induced in rats by ligating the left coronary artery.
- Captopril, an ACE inhibitor, was administered via minipumps at two different timings: early (weeks 1-3) and late (weeks 3-4) post-infarction.
- Cardiac structural changes, including left ventricular dilation, DNA synthesis, and collagen content, were analyzed.
Main Results:
- Early captopril treatment prevented left ventricular dilation and increased collagen content observed after myocardial infarction.
- Early treatment also inhibited the transient increase in DNA synthesis in the remaining left ventricle.
- Late captopril treatment did not significantly alter the structural changes post-myocardial infarction.
Conclusions:
- Early administration of Angiotensin I converting enzyme (ACE) inhibitors may interfere with essential adaptive cardiac remodeling processes following myocardial infarction.
- These negative effects might stem from interactions at the cellular level, disrupting normal responses to myocardial damage.
- The timing of ACE inhibitor therapy is critical and may influence its impact on cardiac structural integrity post-infarction.
Abstract:
Angiotensin I converting enzyme (ACE) inhibitors are widely used in the treatment of heart failure. It is not known whether the beneficial effects of ACE inhibition are only due to a reduction in pre- and afterload or whether ACE inhibition also has direct effects on cardiac remodeling processes after myocardial infarction. In addition, the effects of differential timing of the treatment are not known. The left coronary artery was ligated in rats to induce a myocardial infarction. Control rats received no treatment. Captopril was given via s.c. placed minipumps (500 micrograms/kg.h) in the first 3 weeks or in the third and fourth week after induction of the myocardial infarction. The structural changes of the heart were investigated. Early after ligation the left ventricle was dilated in association with a marked, but transient DNA synthesis in the remaining left ventricle; the amount of collagen also increased. Early captopril treatment blocked this response, while late treatment had no effects. We suggest that the negative effects of early captopril treatment are due to an interference with the normal adaptive responses of the heart to the loss of muscle, probably through interactions at the cellular level.