Long-term treatment with
angiotensin I converting enzyme inhibitors (ACEIs) prolongs survival in rats developing
congestive heart failure after
myocardial infarction (MI). In this experimental model, we investigated at regular intervals the effects of a 1-year oral treatment with
trandolapril, a new ACEI, on (a) survival rate and duration and (b) hemodynamic,
biological, and cardiac and vascular histomorphological parameters. Control MI rats and
sham-operated
trandolapril-treated and control rats were simultaneously studied. In MI rats,
trandolapril significantly increased the survival rate and duration, increasing the life expectancy by approximately 6 months. It also significantly decreased the arterial blood pressure and increased diuresis. These effects occurred as soon as the treatment was started and persisted throughout the study.
Trandolapril significantly limited the development of myocardial
hypertrophy, decreasing the heart weight and left ventricular hypertrophic area and increasing the left ventricular myocyte nuclear density, but these effects, starting after 3-6 months, were delayed compared to the hemodynamic ones. Finally,
trandolapril limited the development of myocardial (both subendocardial and subepicardial) and aortic
fibrosis. It is concluded that the early pre- and afterload effects of
trandolapril are initially responsible for its beneficial action on survival, whereas later the
drug's antihypertrophic and antifibrotic properties together with persistent hemodynamic effects account for the prolonged survival improvement.