Intracoronary nitric oxide improves postischemic coronary blood flow and myocardial contractile function following ischemia and reperfusion. Pabla, Ravinder, Andrew J. Buda, David M. Flynn, Dana B. Salzberg, and David J. Lefer. Department of Medicine, Cardiology Section, Tulane University School of Medicine, 1430 Tulane Avenue, SL-48, New Orleans, Louisiana 70112, U.S.A, and Department of Pharmacology, Division of Biomedical Sciences, King's College, University of London, Manresa Road, London SW3 6LX, U.K.
APStracts 2:0136H, 1995.
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 i.v.) 10 minutes before reperfusion, followed by a 1 mg/hr intracoronary infusion throughout the 4.5 hour reperfusion period, resulted in significant improvement in postischemic transmural myocardial blood flow (0.66 +/- 0.09 ml/min/gram vs. 0.37 +/- 0.08 ml/min/gram for saline vehicle, p < 0.05). Dogs receiving NO supplementation also exhibited a significant recovery of myocardial contractility after 4.5 hours of reperfusion (30 +/- 2% area ejection fraction vs. 22 +/- 2% for saline vehicle, p < 0.05). Moreover, myocardial necrosis as a percent 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. Furthermore, coronary vascular reactivity was examined by injecting acetylcholine and nitroglycerin. 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 hr of reperfusion. However, dogs treated with the NO donor demonstrated postischemic vasodilator responses which were similar to baseline (p = NS 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 nitric oxide administration may be related to the potent anti-neutrophil actions of nitric oxide. 

Received 14 November 1994; accepted in final form 28 March 1995.
APS Manuscript Number H1013-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.