Enhanced Subendocardial Perfusion Distal to a Flow-Limiting Coronary Artery Stenosis in Dogs: Comparative Effects of Nicorandil, a Potential New Antianginal Agent, and Nitroglycerin

The purpose of this study was to compare the effects of nicorandil [SG-75; 2-nicotinamidoethyl nitrate (ester)] and nitroglycerin on the distribution of blood flow between subendocardium and subepicardium [endocardial/epicardial blood flow ratio (endo/epi)] distal to a proximal flow-limiting coronary artery stenosis in anesthetized dogs. Myocardial blood flow distribution was determined by use of 15-μm radioactive microspheres. Various indices of reactive hyperemia (peak flow, duration, volume) and poststenotic coronary pressures were used to assess the severity of ischemia in the area distal to the stenosis. Partial ischemia was produced by a 10-s total left circumflex coronary occlusion followed by 110 s of reflow to 50–60% of the control flow. Microspheres were injected during steady-state conditions during the partial reflow period. In the absence of drug, coronary artery stenosis produced marked underperfusion of the subendocardium (endo/epi, 0.55 ± 0.05). Following administration of nicorandil (60 μg/kg i.v.) or nitroglycerin (15 μg/kg i.v.), the endo-epi during a subsequent partial reflow (stenosis present) period was significantly increased (0.67 ± 0.06). The duration of reactive hyperemia and reactive hyperemic flow were also decreased by both compounds following release of the stenosis. These results suggest that nicorandil and nitroglycerin reduce subendocardial ischemia distal to a flow-limiting coronary artery stenosis. This beneficial effect may partially explain the efficacy of these two compounds in the therapy of angina pectoris.