Treatment of abnormal remodeling and dysfunction of left ventricle after myocardial infarction is one of the major goals of recent therapeutic interventions. The current study, the Nisoldipine Enalapril Anterior Myocardial infarction Study pilot investigation, was designed to investigate the effects of 12 weeks of treatment with enalapril or nisoldipine or their combination on left ventricular (LV) function and exercise capacity in patients with recent (< 1 month) anterior myocardial infarction and mild LV dysfunction (LV ejection fraction [EF] 38% to 48%). Forty-six patients were studied and received, by random assignment, enalapril (5 mg once per day) plus placebo (n = 14) or nisoldipine (10 mg two times per day) plus placebo (n = 18) or enalapril (5 mg once per day) plus nisoldipine (10 mg two times per day) (n = 14). All patients received aspirin (325 mg) throughout the study. Data on LV EF and peak filling rate at rest and LV EF during exercise were collected during radionuclide ventriculography. In addition, the product of heart rate and systolic blood pressure (rate-pressure product) and exercise time were determined during exercise stress testing. The analyzed parameters were not significantly modified after treatment with enalapril or with nisoldipine. In contrast, the combination of enalapril and nisoldipine significantly raised LV EF at rest (from 43% +/- 3% to 48% +/- 6%, p < 0.01) and during exercise (from 45% +/- 8% to 50% +/- 9%, p < 0.01) and raised peak filling rate at rest (fraction of end-diastolic volume per second) from 1.57 +/- 0.3 to 1.67 +/- 0.3 (p < 0.05). In addition, the combined administration of the two drugs increased the rate-pressure product (values x 10(3)) (from 20.7 +/- 5 to 22.7 +/- 4, p < 0.05) and increased exercise time (from 573 +/- 173 seconds to 668 +/- 178 seconds, p < 0.05). These results show that in patients with recent anterior myocardial infarction and mild LV dysfunction, the combination of the angiotensin-converting enzyme inhibitor enalapril and the dihydropyridine nisoldipine improves resting LV systolic and diastolic function and exercise LV systolic function and exercise capacity.