title: Localized administration of sodium nitroprusside enhances its protection against platelet aggregation in stenosed and injured coronary arteries.
abstract: Sodium nitroprusside, a potent vasodilator, was evaluated for its effect on platelet aggregation in stenosed and endothelium-injured coronary arteries in a canine model. Twenty-five anesthetized dogs were studied; coronary blood flow velocity was continuously monitored. Recurrent intracoronary platelet aggregation and dislodgment (indicated by cyclic variations in coronary blood flow) were induced by mechanically injuring and stenosing the left anterior descending coronary artery. Sodium nitroprusside was administered either intrapericardially or intravenously 30 min after cyclic flow variations were established. Intrapericardial administration of saline (control) did not affect cyclic flow variations in any of 6 tested dogs. Sodium nitroprusside abolished cyclic flow variations in all 7 dogs (100%) when given intrapericardially and in 5 to 7 dogs (71%) when given intravenously (compared to intrapericardial salines, p < 0.01). A smaller dose of sodium nitroprusside was required to abolish cyclic flow variations when given intrapericardially than when given intravenously (1.6 +/- 0.5 micrograms.kg-1.min-1 vs 4.8 +/- 0.8 micrograms.kg-1.min-1, p < 0.01). The mean aortic pressure was reduced by 10 to 20 mmHg after intrapericardial sodium nitroprusside administration and by 30 to 40 mmHg after intravenous sodium nitroprusside administration. To investigate the mechanism of protection by sodium nitroprusside, NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthetase, was used to induce cyclic flow variations in mildly injured and stenosed left anterior descending coronary arteries in 5 dogs. Intrapericardial sodium nitroprusside abolished the cyclic flow variations in all 5 dogs. Then oxyhemoglobin, an inhibitor of nitric oxide, was administered into the left anterior descending coronary arteries of these dogs, and it restored the sodium nitroprusside-abolished cyclic flow variations in all 5 dogs. Thus, sodium nitroprusside protects against platelet aggregation and cyclic flow variations in stenosed and endothelium-injured canine coronary arteries, probably by the action of nitric oxide, and it is more effective and hemodynamically safer when administered intrapericardially than when administered intravenously.
authors.affiliation: Cardiovascular Research Laboratory, Texas Heart Institute, Houston, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Willerson
authors.forename: S R
authors.initials: SR
authors.lastname: Igo
authors.forename: S K
authors.initials: SK
authors.lastname: Yao
authors.forename: J C
authors.initials: JC
authors.lastname: Ober
authors.forename: M P
authors.initials: MP
authors.lastname: Macris
authors.forename: J J
authors.initials: JJ
authors.lastname: Ferguson
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D004285:Dogs; D004730:Endothelium, Vascular / Q000293:injuries; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000008:administration & dosage* / Q000494:pharmacology; D010496:Pericardium; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology; D019323:omega-N-Methylarginine
chemical_list: D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase