Willerson J T, Igo S R, Yao S K, Ober J C, Macris M P, Ferguson J J
Cardiovascular Research Laboratory, Texas Heart Institute, Houston, USA.
Tex Heart Inst J. 1996;23(1):1-8.
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.
硝普钠是一种强效血管扩张剂，在犬类模型中评估了其对狭窄和内皮损伤的冠状动脉中血小板聚集的影响。研究了25只麻醉犬；持续监测冠状动脉血流速度。通过机械损伤和狭窄左前降支冠状动脉诱导复发性冠状动脉内血小板聚集和脱落（以冠状动脉血流的周期性变化表示）。在建立周期性血流变化30分钟后，经心包内或静脉内给予硝普钠。心包内给予生理盐水（对照）对6只受试犬中的任何一只的周期性血流变化均无影响。心包内给予硝普钠时，所有7只犬（100%）的周期性血流变化消失；静脉内给予硝普钠时，5至7只犬（71%）的周期性血流变化消失（与心包内生理盐水相比，p<0.01）。心包内给予硝普钠时，消除周期性血流变化所需的剂量比静脉内给予时小（1.6±0.5微克·千克⁻¹·分钟⁻¹对4.8±0.8微克·千克⁻¹·分钟⁻¹，p<0.01）。心包内给予硝普钠后，平均主动脉压降低10至20mmHg；静脉内给予硝普钠后，平均主动脉压降低30至40mmHg。为了研究硝普钠的保护机制，使用一氧化氮合酶抑制剂NG-单甲基-L-精氨酸在5只犬的轻度损伤和狭窄的左前降支冠状动脉中诱导周期性血流变化。心包内给予硝普钠使所有5只犬的周期性血流变化消失。然后，将一氧化氮抑制剂氧合血红蛋白注入这些犬的左前降支冠状动脉，它恢复了硝普钠消除的所有5只犬的周期性血流变化。因此，硝普钠可能通过一氧化氮的作用，防止狭窄和内皮损伤的犬冠状动脉中的血小板聚集和周期性血流变化，并且心包内给药比静脉内给药更有效且血流动力学上更安全。
