Long-term oral treatment with nicorandil prevents the progression of left ventricular hypertrophy and preserves viability.
Left ventricular (LV) hypertrophy and myocardial infarction play important roles in the progressive LV dysfunction. We hypothesized that the potassium-channel opener and nitrate-like vasodilator nicorandil prevents the development of LV hypertrophy and preserves myocardial viability. Twenty-four rats were subjected to aortic stenosis for 8 weeks to produce LV hypertrophy and assigned to non-treated and nicorandil-treated (3 mg/kg/d) groups. A third group (n = 12) without stenosis or treatment served as control. All 36 animals were subjected to reperfused infarction by 25-minute occlusion of the left coronary artery followed by 3 hours of reperfusion. Spin-echo magnetic resonance (MR) images were acquired to measure infarction size, LV mass, volumes, ejection fraction, and wall thickness. A necrosis-specific contrast agent, Gadophrin-3, was used to delineate necrotic myocardium. Aortic and LV pressures were measured invasively. At postmortem, LV mass and infarction size were determined and compared with MR findings. Nicorandil prevented the development of LV hypertrophy. Infarction size of nicorandil-treated animals was similar to control animals. Non-treated animals with aortic banding had higher LV mass (P < 0.001), lower ejection fraction (P = 0.006), and larger infarction size (P < 0.001) than treated and control animals. MR and postmortem data showed close agreement. Nicorandil therapy prevented the development of cardiac hypertrophy and protected myocardium against ischemia.
Schalla
Simon
S
Department of Radiology, University of California San Francisco, San Francisco, CA 94143-0628, USA.
Higgins
Charles B
CB
Saeed
Maythem
M
D000284:Administration, Oral; D000818:Animals; D018450:Disease Progression; D005260:Female; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000517:prevention & control*; D008279:Magnetic Resonance Imaging / Q000379:methods; D020108:Nicorandil / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013995:Time; D014022:Tissue Survival / Q000187:drug effects* / Q000502:physiology
D020108:Nicorandil