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 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.
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Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Buda
A J
AJ
Flynn
D M
DM
Salzberg
D B
DB
Lefer
D J
DJ
D000818:Animals; D002465:Cell Movement; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000503:physiopathology; D004285:Dogs; D005260:Female; D006439:Hemodynamics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009336:Necrosis; D009504:Neutrophils / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*; D014666:Vasomotor System / Q000503:physiopathology
C094475:4-hydroxynethyl-furoxan-3-carboxamide; D010069:Oxadiazoles; D014665:Vasodilator Agents; D009569:Nitric Oxide; D009195:Peroxidase