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


CONCLUSIONS
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.
Watzinger
Norbert
N
Department of Radiology, University of California, San Francisco, 505 Parnassus Avenue, Room L-308, 94143-0628, USA.
Lund
Gunnar K
GK
Higgins
Charles B
CB
Chujo
Mitsuaki
M
Saeed
Maythem
M
D000818:Animals; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020108:Nicorandil / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D014665:Vasodilator Agents / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000473:pathology
D014665:Vasodilator Agents; D020108:Nicorandil