Lorente J A, Landín L, Renes E, De Pablo R, Jorge P, Ródena E, Liste D
Hospital Universitario de Getafe, Madrid, Spain.
Crit Care Med. 1993 May;21(5):759-67. doi: 10.1097/00003246-199305000-00021.
To study the role of nitric oxide in the hemodynamic changes of sepsis.
Prospective, randomized, controlled, intervention study.
Twenty-five sheep randomized to four groups: Group A (n = 8, nonseptic sheep) received NG-nitro L-arginine (20 mg/kg i.v.) followed 15 mins later by L-arginine (200 mg/kg i.v.); group B (n = 4, nonseptic sheep) received L-arginine followed 15 mins later by NG-nitro L-arginine; group C (n = 7, septic sheep) received NG-nitro L-arginine (20 mg/kg i.v.) alone; group D (n = 6, septic sheep) received L-arginine (200 mg/kg i.v.) followed by NG-nitro L-arginine (20 mg/kg i.v.).
Sheep were anesthetized with pentobarbital, mechanically ventilated and monitored with a pulmonary artery catheter, a peripheral artery catheter, and a Miller catheter in the left ventricle. Sepsis was induced by the intravenous administration of live Escherichia coli (1.5 x 10(9) microorganisms/kg over 30 mins), which resulted in systemic hypotension, pulmonary hypertension, high cardiac output, and hyperlactatemia. Acetylcholine was administered before and after each intervention.
In nonseptic sheep (groups A and B) NG-nitro L-arginine induced an increase in mean blood pressure (BP), pulmonary arterial pressure, and systemic and pulmonary vascular resistances, accompanied by a decrease in cardiac index and the first derivative of left ventricular pressure. L-arginine administered to normal sheep induced systemic vasodilation. In the sepsis groups (groups C and D), the increases in BP and systemic vascular resistances induced by NG-nitro L-arginine were significant but less marked than in nonseptic sheep. Pretreatment of septic sheep with L-arginine totally abolished the NG-nitro L-arginine induced increases in systemic and pulmonary vascular resistances in this group. The administration of L-arginine in these animals induced both systemic and pulmonary vasodilation. Acetylcholine-mediated vasodilation was severely impaired in sepsis. In this condition, pretreatment with L-arginine improved the response to acetylcholine.
These data support the view that nitric oxide plays a significant role in modulating systemic and pulmonary vasomotor tone in normal and septic sheep. L-arginine produced systemic vasodilation in normal sheep, whereas both systemic and pulmonary vasodilation were observed in septic animals. The impaired response to an endothelium-dependent vasodilator in sepsis was improved by the previous administration of L-arginine.
研究一氧化氮在脓毒症血流动力学变化中的作用。
前瞻性、随机、对照、干预性研究。
25只绵羊随机分为四组：A组（n = 8，非脓毒症绵羊）静脉注射NG-硝基-L-精氨酸（20 mg/kg），15分钟后静脉注射L-精氨酸（200 mg/kg）；B组（n = 4，非脓毒症绵羊）先静脉注射L-精氨酸，15分钟后静脉注射NG-硝基-L-精氨酸；C组（n = 7，脓毒症绵羊）仅静脉注射NG-硝基-L-精氨酸（20 mg/kg）；D组（n = 6，脓毒症绵羊）先静脉注射L-精氨酸（200 mg/kg），随后静脉注射NG-硝基-L-精氨酸（20 mg/kg）。
绵羊用戊巴比妥麻醉，机械通气，并通过肺动脉导管、外周动脉导管和左心室内的米勒导管进行监测。通过静脉注射活的大肠杆菌（30分钟内注射1.5×10⁹个微生物/kg）诱导脓毒症，这导致了全身低血压、肺动脉高压、高心输出量和高乳酸血症。在每次干预前后给予乙酰胆碱。
在非脓毒症绵羊（A组和B组）中，NG-硝基-L-精氨酸导致平均血压（BP）、肺动脉压、全身和肺血管阻力增加，同时心指数和左心室压力的一阶导数降低。给正常绵羊注射L-精氨酸可引起全身血管舒张。在脓毒症组（C组和D组）中，NG-硝基-L-精氨酸引起的BP和全身血管阻力增加是显著的，但不如非脓毒症绵羊明显。用L-精氨酸预处理脓毒症绵羊可完全消除该组中NG-硝基-L-精氨酸引起的全身和肺血管阻力增加。给这些动物注射L-精氨酸可引起全身和肺血管舒张。脓毒症时乙酰胆碱介导的血管舒张严重受损。在这种情况下，用L-精氨酸预处理可改善对乙酰胆碱的反应。
这些数据支持以下观点，即一氧化氮在调节正常和脓毒症绵羊的全身和肺血管舒缩张力中起重要作用。L-精氨酸在正常绵羊中引起全身血管舒张，而在脓毒症动物中观察到全身和肺血管舒张。脓毒症时对内皮依赖性血管舒张剂反应受损，通过预先给予L-精氨酸得到改善。
