Effects of nicorandil, a new antianginal agent, and nifedipine on collateral blood flow in a chronic coronary occlusion model

Abstract

The effects of nicorandil and nifedipine on collateral blood flow were compared in anesthetized dogs with a well-developed collateral circulation produced by Ameroid constriction (6-8 weeks) of the left anterior descending (LAD) coronary artery. The radioactive microsphere technique was used to determine myocardial perfusion in the normal left circumflex (LC) region and in the LAD region distal to the Ameroid constrictor. Low and high doses of nicorandil (25 and 50 micrograms/kg/min) or nifedipine (1 and 3 micrograms/kg/min) were infused i.v. to reduce mean arterial and left ventricular systolic pressure approximately 10 and 25 mm Hg, respectively. A low dose of nicorandil had no effect on myocardial perfusion whereas nifedipine increased subepicardial blood flow in both the LC and LAD regions. The high dose of nifedipine further increased both subepicardial and subendocardial perfusion to the LC region and subepicardial blood flow to the LAD region whereas nicorandil had no effect. When aortic blood pressure was returned to control by occluding a snare around the descending thoracic aorta during infusion of the high dose, nicorandil and nifedipine increased subepicardial and subendocardial blood flow to LAD and LC regions. Whereas nicorandil increased flow to both tissue layers equally, nifedipine increased subepicardial perfusion primarily. In summary, nifedipine increased collateral blood flow in a chronic coronary occlusion model despite the presence of systemic hypotension, whereas nicorandil only increased flow when aortic blood pressure was maintained. However, nicorandil increased myocardial blood flow equally across the left ventricular wall, whereas nifedipine primarily increased subepicardial blood flow.