The effects of short- and long-term treatment with an ACE-inhibitor in rats with myocardial infarction

It has been shown that converting enzyme inhibitors (CEI) attenuate ventricular dilatation and hypertrophy after myocardial infarction. In most studies, CEI treatment was started when ventricular dilatation and hypertrophy were already well under way. Therefore, we studied the effects on ventricular dilatation and hypertrophy, when CEI treatment was started in the acute phase of myocardial infarction. Immediately after a sham-operation or myocardial infarction in rats (sham: n = 8; MI: n = 17), treatment with zofenopril, a novel ACE-inhibitor, was started and continued during 42 days (long-term treatment). In a second group of rats, zofenopril was administered only during the first 5 days after myocardial infarction (short-term treatment); these rats were not treated with zofenopril during the remaining period of 37 days (sham: n = 5; MI: n = 13). Untreated rats served as controls (sham: n = 9; MI: n = 24). The results from this study showed that long-term treatment with zofenopril caused a significant reduction of left ventricular cavity volume in rats with moderate-to-large infarctions, which was accompanied by a significant reduction in the ratio of total heart weight to body weight. However, short-term treatment with zofenopril did not significantly reduce ventricular volume or total heart weight. Finally, both long- and short-term treatment resulted in a small, but statistically significant, reduction of septal wall thickness in sham-operated and infarcted rats.

We conclude that CEI therapy decreases ventricular dilatation and hypertrophy after myocardial infarction, only when treatment is continued during the chronic phase. Although a tendency to reduction can be observed, ventricular enlargement is not significantly affected when CEI therapy is confined to the acute phase of myocardial infarction. Interestingly, CEI therapy confined to the acute phase of myocardial infarction significantly decreases septal wall thickness, suggesting a reduction in left ventricular hypertrophy. It is questionable whether this reduction in septal wall thickness is beneficial, because this effect was not associated with a reduction in total cardiac weight and lung weight, indicating that (right) ventricular hypertrophy and pulmonary congestion are still present, unlike in rats chronically treated with zofenopril.