In the present study a novel
nitric oxide (NO) donor,
CAS-1609, was utilized as a means of coronary NO replenishment in a canine model of
myocardial ischemia-reperfusion. Administration of
CAS-1609 (1.25 mg iv) 10 min before reperfusion, followed by a 1 mg/h intracoronary infusion throughout the 4.5-h reperfusion period, resulted in significant improvement 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 recovery of myocardial contractility after 4.5 h of reperfusion (30 +/- 2% area ejection fraction vs. 22 +/- 2% for saline vehicle, P < 0.05). Moreover, myocardial
necrosis as a percentage of the area at risk was reduced from 28.9 +/- 4.3% in the saline group to 8.5 +/- 2.6% in the
CAS-1609 group (P < 0.01), while ischemic zone
myeloperoxidase activity, indicative of neutrophil infiltration, was also attenuated by 70% with NO
therapy. Injection of
acetylcholine and
nitroglycerin into the left circumflex coronary artery revealed a significant impairment of
vasodilator responses in the saline vehicle dogs at 2 h of reperfusion. However, dogs treated with the NO donor demonstrated postischemic
vasodilator responses which were similar to baseline (P = not significant vs. baseline). These studies demonstrate that intracoronary administration 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
necrosis, and reduces neutrophil infiltration. The cardioprotective actions of intracoronary NO administration may be related to the potent antineutrophil actions of NO.