REDUCTION IN INFARCT SIZE BY CHRONIC AMLODIPINE TREATMENT IN CHOLESTEROL-FED RABBITS

Calcium (Ca)-dependent factors, including cholesterol-induced changes in membrane Ca permeability and Ca deposition into lesions, may contri bute to plaque formation and stability during the early and late stage s of atherogenesis. Amlodipine can reduce atheroma formation in choles terol-fed rabbits and may be cardioprotective. We therefore examined t he effects of chronic amlodipine treatment (5 mg/kg daily for 10 weeks , p.o.) on infarct size after 30-min coronary occlusion/48-h reperfusi on in rabbits fed a diet with or without 1% cholesterol. Infarct size was significantly larger in cholesterol-fed rabbits (72.0 +/- 3.5%, n = 9, mean +/- S.E.M.) than in normal-fed rabbits (47.1 +/- 4.9%, n = 9 , P < 0.05). Amlodipine treatment effectively reversed the infarct siz e augmentation in cholesterol-fed rabbits (46.3 +/- 6.3%, n = 9, P < 0 .05), but did not affect infarct size in normal-fed rabbits (51.0 +/- 4.7%, n = 8). In both cholesterol-fed and normal-fed rabbits, Ca conte nt and leukocyte accumulation as assessed by myeloperoxidase activity were significantly higher in the ischemic myocardium than in the nonis chemic myocardium. However, Ca content and leukocyte accumulation were markedly elevated in the ischemic myocardium of cholesterol-fed rabbi ts compared with normal-fed rabbits. Amlodipine treatment effectively reversed this elevation. Acetylcholine showed a marked reduction in en dothelium-dependent relaxation in the aorta of cholesterol-fed rabbits , which also was reversed by amlodipine treatment. These results indic ate that chronic amlodipine treatment reduces infarct size only in cho lesterol-fed rabbits. (C) 1998 Elsevier Science Ireland Ltd. All right s reserved.