Noninvasive assessment of the effects of nicorandil on left ventricular volumes and function in reperfused myocardial infarction.

Abstract

Nicorandil, a K-ATP channel opener with a nitrate-like effect, is a potent vasodilator and has favorable hemodynamic effects in heart failure patients. While its cardio-protective properties in the setting of acute ischemia are well known, the long-term effects of oral nicorandil therapy on post-infarction left ventricular (LV) dilatation have not been investigated. Myocardial infarction (MI) was induced in 30 Sprague-Dawley rats by 1 h of coronary artery occlusion followed by reperfusion. After matching for infarction size, animals were randomly assigned to nicorandil treatment (3 mg/kg/day) given in tap water or no treatment (control group). Treatment was started 2 days after MI and continued for 8 weeks. Contrast-enhanced and functional magnetic resonance imaging (MRI) were used to determine infarction size, LV volumes, mass, ejection fraction, and regional wall thickness. Nicorandil significantly decreased end-systolic volumes (0.33+/-0.02 ml; P<0.05) and improved LV ejection fraction (37+/-2%; P<0.01) compared to control rats (0.43+/-0.04 ml and 28+/-2%, respectively) 8 weeks after MI. During the study period, the increase in LV mass (DeltaLVM) was significantly greater in control (0.09+/-0.03 g) than in treated animals (0.02+/-0.02 g, P<0.05). Moreover, nicorandil improved systolic wall thickening of the rim of infarction (P<0.001) and remote non-infarcted regions (P<0.01). These results demonstrate that the long-term oral treatment with nicorandil started 2 days after MI attenuates left ventricular dilatation and improves cardiac function in rats with reperfused MI.