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Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril
Insights
Long-term captopril therapy improved survival in rats after myocardial infarction, particularly in those with moderate-sized infarcts. Survival was inversely related to infarct size in this study.
Area of Science:
- Cardiovascular Research
- Pharmacology
Background:
- Vasodilator therapy improves functional capacity in congestive heart failure but lacks survival benefits.
- Myocardial infarction leads to left ventricular dysfunction, with survival inversely related to infarct size.
Purpose of the Study:
- To determine the relationship between myocardial infarction size and long-term survival.
- To test if long-term captopril therapy improves survival after myocardial infarction.
Main Methods:
- 302 rats underwent coronary artery ligation to induce varying infarct sizes.
- Rats were randomized to placebo or captopril therapy 14 days post-ligation.
- Animals were monitored for 1 year, with infarct size determined histologically.
Main Results:
- One-year survival decreased with increasing infarct size in placebo-treated rats (71% to 8%).
- Captopril therapy significantly prolonged survival in rats with infarcts (p < .02).
- Moderate infarcts showed the most benefit, with survival increasing from 21% (placebo) to 48% (captopril).
Conclusions:
- Survival after myocardial infarction is inversely related to infarct size.
- Long-term captopril therapy significantly prolongs survival in experimental myocardial infarction.
- Captopril demonstrates a pronounced survival-prolonging effect in chronic infarction with left ventricular dysfunction.
Abstract:
Although vasodilator therapy has been shown to improve functional capacity in patients with congestive heart failure, there is no evidence that such therapy can prolong survival. Coronary artery ligation in the rat was used to produce a wide range of myocardial infarct sizes and a resultant spectrum of left ventricular dysfunction. To determine the relationship between size of myocardial infarction and long-term survival and to test the hypothesis that long-term therapy with captopril could improve survival after myocardial infarction, 302 rats were randomly assigned to either placebo or captopril therapy 14 days after coronary artery ligation. The animals were kept in a laminar flow unit and followed daily for a 1 year period or until spontaneous death. Size of myocardial infarction was determined by planimetry of serial histologic sections of the left ventricle. One year survival in placebo-treated rats decreased markedly in direct relation to increasing size of infarction (from 71% in noninfarcted rats to only 8% in rats with large infarcts). Long-term captopril therapy prolonged the survival of rats with infarcts (p less than .02). The most marked improvement in survival was noted in the animals with infarcts of moderate size, in which 1 year survival was 21% in the placebo-treated rats and 48% in the captopril-treated rats. Thus, in this experimental preparation of myocardial infarction and left ventricular dysfunction, survival was inversely related to size of infarction. Long-term therapy with captopril, which we had previously shown to improve left ventricular function and lessen dilatation in the chronic phase of infarction, also had a pronounced effect on prolonging survival in this preparation of chronic infarction.