Effects of amlodipine on myocardial infarction, infarct expansion, and ventricular geometry in the rat

Abstract

Infarct expansion remains an important sequela of myocardial infarction. Both angiotensin converting enzyme inhibitors and intravenous nitrates reduce early infarct expansion in humans. This is believed to be caused by the reduction in left ventricular systolic wall stress that results from the arteriolar vasodilatation they produce. Patients are frequently already receiving calcium channel blockers at the time of infarction or these drugs are sometimes administered in the perimyocardial infarction period. The calcium blockers of the dihydropyridine class might be expected to modify infarct expansion. However, their effect on this process has not been studied. We therefore evaluated the effect of early treatment with the calcium blocker amlodipine, a potent arteriolar vasodilator with minimal negative inotropic properties, on chronic myocardial infarction in the rat. Permanent left coronary occlusion was created after pretreatment with amlodipine, 0.25 mg/kg (low dose) or 1.0 mg/kg (high dose), or placebo, intravenously twice a day, and continued for 7 days after infarction. Hearts ( n = 50) were perfusion fixed 21 days after infarction and analyzed for infarct extent, scar thickness, left ventricular shape and size, and expansion index. Both doses decreased mean blood pressure (119 ± 3 to 99 ± 5 mm Hg low dose, p = 0.004; 110 ± 5 to 84 ± 4 mm Hg high dose, p = 0.0003), with reflex tachycardia only after the high dose (heart rate 395 ± 9 to 434 ± 11, p = 0.001). Infarct extent was equal in the three groups (39 ± 2%, 41 ± 2%, and 41 ± 3% of left ventricular circumference for control, low, and high doses, respectively). The three groups did not differ significantly with regard to left ventricular cavity cross-sectional area (80 ± 4, 77 ± 3, and 87 ± 3 mm 2, control, low, and high doses, respectively; p = 0.07 high dose vs control), mean scar thickness (0.74 ± 0.06, 0.73 ± 0.05, and 0.65 ± 0.06 mm, control, low, and high doses, respectively; p = NS), and expansion index (1.52 ± 0.10, 1.58 ± 0.12, and 1.95 ± 0.19, control, low, and high doses, respectively; p = 0.08 high dose vs control). In the subgroup with larger infarcts (infarct extent >0.39 of left ventricle), the expansion index was higher in the high-dose group (2.37 ± 0.23 vs 1.64 ± 0.17 control; p = 0.04). In this model, treatment with amlodipine does not limit infarct extent or reduce early infarct expansion and left ventricular dilatation, even when initiated before infarction. It is likely that administration of an arteriolar vasodilator agent alone does not limit early infarct expansion; effective adjuvant agents probably operate by other mechanisms.