INTRAVENOUS NITROGLYCERIN INFUSION INHIBITS CYCLIC BLOOD-FLOW RESPONSES CAUSED BY PERIODIC PLATELET THROMBUS FORMATION IN STENOSED CANINE CORONARY-ARTERIES
INTRAVENOUS NITROGLYCERIN INFUSION INHIBITS CYCLIC BLOOD-FLOW RESPONSES CAUSED BY PERIODIC PLATELET THROMBUS FORMATION IN STENOSED CANINE CORONARY-ARTERIES
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DOI：
10.1161/01.cir.83.6.2122
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发表时间：
1991-06-01
期刊：
影响因子：
37.8
通讯作者：
LOSCALZO, J
中科院分区：
文献类型：
--
作者：
FOLTS, JD;STAMLER, J;LOSCALZO, J
背景。硝酸甘油和其他临床相关的有机硝酸盐衍生物已被证明在体外抑制血小板聚集。硝酸盐的这种抗血栓作用通过还原硫醇而增强。为了确定这种作用机制在体内的潜在相关性，我们在犬冠状动脉狭窄模型中检测了静脉输注硝酸甘油对周期性血小板血栓形成的影响。方法与结果。我们使用了一个犬冠状动脉狭窄模型，该模型与冠状动脉血流循环减少有关，这已被证明依赖于周期性血小板血栓形成。我们量化了每40分钟观察周期的周期频率，并监测持续静脉输注硝酸甘油对周期频率的影响。施用10-15 μ g/kg/min硝酸甘油可显著减少循环血小板血栓形成，且冠状动脉血流无明显变化。经还原性巯基n -乙酰半胱氨酸预处理（100 mg/kg， 30分钟），硝酸甘油静脉注射可抑制循环血小板血栓形成，单独剂量（5 μ g/kg/min）无此作用。这些数据表明，静脉注射硝酸甘油改善急性冠状动脉疾病综合征缺血的一种机制可能是通过抑制血小板血栓形成，并可能强调在这一机制中还原性硫醇的潜在重要性。
Background. Nitroglycerin and other clinically relevant organic nitrate derivatives have been shown to inhibit platelet aggregation in vitro. This antithrombotic effect of nitrates is potentiated by reduced thiol. To determine the potential relevance of this mechanism of action in vivo, we examined the effect of intravenous nitroglycerin infusion on periodic platelet thrombus formation in a canine model of coronary artery stenosis.Methods and Results. We used a canine model of coronary artery stenosis associated with cyclic reductions in coronary blood flow that have been shown to depend on periodic platelet thrombus formation. We quantified the frequency of cycles per 40-minute observation period and monitored the effect of a continuous infusion of intravenous nitroglycerin on the cycle frequency. The administration of 10-15-mu-g/kg/min nitroglycerin reduced cyclic platelet thrombus formation significantly and did so without a significant change in coronary artery blood flow. Pretreatment with the reduced thiol, N-acetylcysteine (100 mg/kg during 30 minutes), led to inhibition of cyclic platelet thrombus formation by intravenous nitroglycerin at doses that alone had no such effect (5-mu-g/kg/min).Conclusion. These data suggest that one mechanism by which intravenous nitroglycerin improves ischemia in acute coronary artery disease syndromes may be by inhibition of platelet thrombus formation and may highlight the potential importance of reduced thiol in this mechanism.