Effects of chronic oral administration of nifedipine and diltiazem on occlusive thrombus of small coronary arteries in (NZW × BXSB)F1 male mice

Objective: (NZW × BXSB)F1 male mice were used as a model to study the effects of chronic administration of nifedipine and diltiazem on small coronary artery disease and mortality. Methods: 16 week old (NZW × BXSB)F1 male mice were given either nifedipine (n=29) at 20 mg·kg−1·d−1 orally or diltiazem (n=28) at 100 mg·kg−1·d−1 orally in two divided doses until they were 24 weeks old (ie, for 60 d). Age matched control mice were given an equivalent volume of vehicle (n=30). Mice that died received immediate necropsy. After 60 d, all surviving mice were killed and hearts and kidneys were examined histologically. Results: The survival rate at 24 weeks was significantly higher in mice given nifedipine than in the controls (71% and 47%, respectively, p<0.05). The number of mice with myocardial necrosis, scar formation, or both, the percentage of areas of the ventricular wall with myocardial necrosis and scar formation, and the number of mice with small intramyocardial arteries showing ≥ 75% stenosis were all significantly lower in the mice given nifedipine than in the controls. In the mice given diltiazem, there were no such differences from the controls. There was no evidence of significant stenosis or thrombosis in the extramyocardial coronary arteries in any of the mice. Systolic blood pressure and the rate-pressure product at 24 weeks of age, as well as the histological score for glomerulonephritis changes, were significantly lower in mice given nifedipine or diltiazem than in the controls. Conclusions: Despite an equivalent improvement of systolic blood pressure, the double product, and renal disease in nifedipine treated and diltiazem treated mice, only nifedipine prevented small coronary artery disease and increased the survival of (NZW × BXSB)F1 male mice, suggesting that nifedipine prevents occlusive thrombi of small coronary arteries better than diltiazem.