Effects of Nisoldipine, A New Calcium Antagonist, on Myocardial Infarct Size and Cardiac Dynamics Following Acute Myocardial Infarction

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Abstract
While some calcium antagonists are effective in reducing myocardial infarct size, this beneficial effect may be accompanied by negative inotropic effects. In the following study, a new dihydropyridine calcium antagonist, nisoldipine, was assessed for its effect on infarct size, hemodynamics, and regional function as assessed by percent systolic wall thickening of the left ventricle (SWT) by 2D echocardiography. Open-chest, anesthetized dogs were subjected to 6 h of coronary artery occlusion. After 10 min of coronary artery occlusion, the ischemic area at risk of infarction (AR:% of left ventricle) was determined by left atrial injection of 99mTc-labeled albumin microspheres with subsequent postmortem autoradiography. After 6 h, the hearts were excised, and the area of necrosis (AN) determined by incubation of left ventricular slices in triphenyltetrazolium chloride stain. Treated dogs received 0.005 mg/kg nisoldipine by intravenous infusion at 1.91 ml/min (lasting ∼8.7 min) during three dosing periods: 15 min. 2 h, and 4 h postocclusion. The AR of eight controls (25.7 ± 1.8%) was not significantly different from that of 11 treated dogs (25.1 ± 1.9%). However, the AN/AR × 100 of treated dogs was significantly less than that of controls (62.8 ± 9.3 vs. 91.6 ± 7.0%; p < 0.05). Mean arterial pressure fell in treated dogs by 15.7% (p < 0.01) at 15 min and by 5.7% (p < 0.05) at 4 h but not at 2 h postocclusion. Heart rate was not affected by nisoldipine. The percent SWT of the ischemic zone (6 h post-coronary artery occlusion) was similar in nisoldipine-treated (−4 ± 5%) and control dogs (−7 ± 10%); percent SWT of the nonischemic zone was similar in nisoldipine-treated (27 ± 4%) and control (18 ± 6%) dogs (p = not significant). The dP/dt was similar in nisoldipine-treated and control dogs at 2,020 ± 169 and 2,267 ± 353 mm Hg/s, respectively. We conclude that nisoldipine reduces myocardial infarct size and afterload without producing negative inotropic or negative chronotropic effects.