EFFECTS OF A NITRIC-OXIDE SYNTHASE INHIBITOR IN HUMANS WITH SEPTIC SHOCK
EFFECTS OF A NITRIC-OXIDE SYNTHASE INHIBITOR IN HUMANS WITH SEPTIC SHOCK
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DOI：
10.1093/cvr/28.1.34
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发表时间：
1994-01-01
影响因子：
10.8
通讯作者：
VALLANCE, P
中科院分区：
文献类型：
--
作者：
PETROS, A;LAMB, G;VALLANCE, P
目的：动物研究表明，一氧化氮合酶诱导型一氧化氮的产生增加有助于内毒素和细胞因子诱导的休克的病理生理学。本研究的目的是确定一氧化氮在人类感染性休克中的作用。方法：该研究是一项随机、双盲、安慰剂对照研究，研究一氧化氮合酶抑制剂 N(G) 单甲基-L-精氨酸 (L-NMMA) 对 12 名伴有低血压的严重脓毒症患者的影响。进行血液动力学、血液学和生化变量的测量。结果：L-NMMA（0.3 和 1 mg-kg-1）导致平均动脉压、全身血管阻力、肺血管阻力、中心静脉压和肺动脉闭塞压呈剂量依赖性增加，并导致心输出量和心率下降。响应最高剂量的L-NMMA，全身血管阻力从547（SEM 92）增加到889（143）dyne.s.cm-5，平均动脉血压从80.9（2.9）增加到100.5（6.1）mm Hg，心输出量从11.2（2.1）减少到8.9（1.9）litres.min-1。连续输注 L-NMMA (1 mg-kg-1.h-1) 产生持续的血流动力学变化。在研究过程中，L-NMMA 组和安慰剂组的血小板数量均有所下降，并且各组之间没有显着差异。结论：低剂量的 L-NMMA 会导致感染性休克患者血管张力广泛增加并导致血压升高。一氧化氮的过量产生似乎是患者感染性休克的重要机制，抑制一氧化氮的合成可能为这种情况提供一种新的治疗方法。然而，L-NMMA 会导致心输出量下降，这可能会恶化组织灌注。现在需要更大规模的研究来检验 L-NMMA 对死亡率和发病率的影响。
Objective: Studies in animals have indicated that increased production of nitric oxide from an inducible isoform of nitric oxide synthase contributes to the pathophysiology of endotoxic and cytokine induced shock. The aim of this study was to determine the role of nitric oxide in septic shock in humans. Methods: The study was a randomised, double blind, placebo controlled investigation of the effects of the nitric oxide synthase inhibitor N(G) monomethyl-L-arginine (L-NMMA) in 12 patients with severe sepsis associated with hypotension. Measurements of haemodynamic, haematological, and biochemical variables were made. Results: L-NMMA (0.3 and 1 mg-kg-1) produced a dose dependent increase in mean arterial pressure, systemic vascular resistance, pulmonary vascular resistance, central venous pressure, and pulmonary artery occlusion pressure, and a decrease in cardiac output and heart rate. In response to the highest dose of L-NMMA systemic vascular resistance increased from 547(SEM 92) to 889(143) dyne.s.cm-5, mean arterial blood pressure increased from 80.9(2.9) to 100.5(6.1) mm Hg, and cardiac output decreased from 11.2(2.1) to 8.9(1.9) litres.min-1. Continuous infusion of L-NMMA (1 mg-kg-1.h-1) produced sustained haemodynamic changes. Platelet numbers decreased during the course of the study in both the L-NMMA and the placebo group and did not differ significantly between the groups. Conclusions: Low doses of L-NMMA cause a widespread increase in vascular tone and raise blood pressure in patients with septic shock. Overproduction of nitric oxide appears to be an important mechanism in septic shock in patients, and inhibition of nitric oxide synthesis might provide a novel therapeutic approach to this condition. However, L-NMMA produced a fall in cardiac output and it is possible that this would worsen tissue perfusion. Larger studies examining the effects of L-NMMA on mortality and morbidity are now required.