Comparative Effects of a New Nicotinamide Nitrate Derivative, Nicorandil (SG 75), with Nifedipine and Nitroglycerin on True Collateral Blood Flow Following an Acute Coronary Occlusion in Dogs

The effects of nicorandil (NC), nifedipine (NF), and nitroglycerin (GTN) on true collateral blood flow were studied following an acute occlusion of the left anterior descending (LAD) coronary artery in anesthetized dogs. Ischemic tissue samples contaminated with overlap blood flow from the normal region were eliminated by using a special balloon reservoir technique for administration of radioactive microspheres. The effects of each drug on true collateral blood flow were determined following 1 h of coronary occlusion with the radioactive microsphere technique and an indirect index of collateral perfusion, retrograde pressure. NC (25 micrograms/kg/min, i.v.), NF (1.0 micrograms/kg/min, i.v.), and GTN (1.5 micrograms/kg/min, i.v.) infusions reduced mean arterial and left ventricular systolic pressures similarly (10-20 mm Hg). None of the drugs had any effect on true collateral blood flow in the presence of a decrease in aortic blood pressure. However, when aortic pressure was maintained by use of a cuff around the descending thoracic aorta, NC and NF increased collateral flow as measured by the microsphere technique as well as retrograde pressure. In addition, NC produced a significant increase in subendocardial blood flow, which resulted in an increase in the endocardial-epicardial blood flow ratio (endo/epi). GTN had no significant effect on any index of collateral function. These results indicate the importance of aortic pressure in determining the effects of vasodilators on coronary collateral function. Furthermore, NC may have more desirable effects on collateral blood flow than NF or GTN when hypotension is minimized, since this was the only agent that selectively increased subendocardial blood flow.