INTRACORONARY NITRIC-OXIDE IMPROVES POSTISCHEMIC CORONARY BLOOD-FLOW AND MYOCARDIAL CONTRACTILE FUNCTION

In the present study a novel nitric oxide (NO) donor, CAS-1609, was ut ilized as a means of coronary NO replenishment in a canine model of my ocardial ischemia-reperfusion. Administration of CAS-1609 (1.25 mg iv) 10 min before reperfusion, followed by a 1 mg/h intracoronary infusio n throughout the 4.5-h reperfusion period, resulted in significant imp rovement in postischemic transmural myocardial blood flow (0.66 +/- 0. 09 vs. 0.37 +/- 0.08 ml . min(-1). g(-1) for saline vehicle, P < 0.05) . Dogs receiving NO supplementation also exhibited a significant recov ery of myocardial contractility after 4.5 h of reperfusion (30 +/- 2% area ejection fraction vs. 22 +/- 2% for saline vehicle, P < 0.05). Mo reover, myocardial necrosis as a percentage of the area at risk was re duced from 28.9 +/- 4.3% in the saline group to 8.5 +/- 2.6% in the CA S-1609 group (P < 0.01), while ischemic zone myeloperoxidase activity, indicative of neutrophil infiltration, was also attenuated by 70% wit h NO therapy. Injection of acetylcholine and nitroglycerin into the le ft circumflex coronary artery revealed a significant impairment of vas odilator responses in the saline vehicle dogs at 2 h of reperfusion. H owever, dogs treated with the NO donor demonstrated postischemic vasod ilator responses which were similar to baseline (P = not significant v s. baseline). These studies demonstrate that intracoronary administrat ion of NO significantly augments postischemic coronary blood flow and contractile function following ischemia and reperfusion. In addition, NO therapy reduces coronary vascular injury, attenuates myocardial nec rosis, and reduces neutrophil infiltration. The cardioprotective actio ns of intracoronary NO administration may be related to the potent ant ineutrophil actions of NO.