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Cardiovascular Research 2002 54(1):77-84; doi:10.1016/S0008-6363(01)00556-9
© 2002 by European Society of Cardiology
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Copyright © 2002, European Society of Cardiology

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

Norbert Watzingera,1, Gunnar K. Lunda, Charles B. Higginsa, Mitsuaki Chujob and Maythem Saeeda,*

aDepartment of Radiology, University of California, San Francisco, 505 Parnassus Avenue, Room L-308, San Francisco, CA 94143-0628, USA
bChugai Pharmaceutical Co. Ltd., Tokyo, Japan

* Corresponding author. Tel.: +1-415-476-0439; fax: +1-415-476-0616 maythem.saeed{at}radiology.ucsf.edu

Objective: 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. Methods: 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. Results: 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 ({Delta}LVM) 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). Conclusion: 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.

KEYWORDS K-ATP channel; Infarction; Heart failure; NMR

1 Present address: Department of Medicine, University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria.


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[Abstract] [Full Text] [PDF]


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