EFFECTS OF NITRIC-OXIDE SYNTHESIS INHIBITION IN HYPERDYNAMIC ENDOTOXEMIA
EFFECTS OF NITRIC-OXIDE SYNTHESIS INHIBITION IN HYPERDYNAMIC ENDOTOXEMIA
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DOI：
10.1097/00003246-199402000-00023
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发表时间：
1994-02-01
影响因子：
8.8
通讯作者：
TRABER, DL
中科院分区：
文献类型：
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作者：
MEYER, J;LENTZ, CW;TRABER, DL
目的：研究一氧化氮合成抑制剂N ω-硝基-L-精氨酸甲酯对高动力性脓毒症绵羊模型血流动力学、气体交换和氧转运的影响。设计：前瞻性、非随机、对照研究，重复测量。设置：大学研究实验室。研究对象：20只健康成年绵羊（体重20 ~ 45 kg）分为两组，每组12只处理组和8只对照组。干预措施：20只清醒的慢性仪器绵羊接受了48小时内的内毒素（10 ng/kg/min）连续输注。内毒素输注开始后24小时，12只绵羊（治疗组）接受一氧化氮合成抑制剂N ω-硝基-L-精氨酸甲酯（25 mg/kg）的推注，而其他8只动物（对照组）接受载体（0.9% NaCl）。测量和主要结果：内毒素输注开始后24小时，两组均表现出高动力状态，心脏指数增加，全身血管阻力指数降低，氧合受损，肺分流分数增加。在两组中，氧输送显著增加，而氧消耗几乎保持不变，导致氧提取率降低。在对照组中，全身血流动力学、肺功能和氧转运的显著变化持续到研究的剩余时间。N ω-硝基-L-精氨酸甲酯的给药使心脏指数和全身血管阻力指数正常化，平均动脉血压升高，心率降低。虽然在施用N ω-硝基-L-精氨酸甲酯后氧输送显著降低，但氧消耗没有改变，导致氧提取率正常化。尽管肺分流率显著降低，但氧合并未改善。肺动脉压和肺血管阻力指数在一氧化氮合成抑制剂给药后2小时出现峰值，随后呈下降趋势。相比之下，N ω-硝基-L-精氨酸甲酯对体循环的影响持续到研究的剩余时间。结论：这些数据支持这样的假设，即一氧化氮的产生增加是高动力性内毒素血症血流动力学改变的主要原因。施用一氧化氮合成抑制剂N ω-硝基-L-精氨酸甲酯使内毒素诱导的高动力状态正常化，但不损害氧消耗，表明代谢活性器官的充分组织灌注。当常规治疗不能维持最低限度的心血管功能时，抑制一氧化氮合成可能是治疗高动力性脓毒症患者的一种治疗选择。
Objective: To investigate the effects of N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis, on hemodynamics, gas exchange and oxygen transport in an ovine model of hyperdynamic sepsis. Design: Prospective, nonrandomized, controlled study, with repeated measurements. Setting: University research laboratory. Subjects:Twenty healthy adult sheep (weighing 20 to 45 kg) were divided into two groups of 12 treated sheep and eight control sheep and studied. Interventions: Twenty awake, chronically instrumented sheep received a continuous infusion of endotoxin (10 ng/kg/min) over 48 hrs. Twenty-four hours after the start of the endotoxin infusion, 12 sheep (treatment group) received a bolus of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (25 mg/kg), while the other eight animals (control group) received the carrier (0.9% NaCl). Measurements and Main Results: Twenty-four hours after the start of the endotoxin infusion, both groups exhibited a hyperdynamic state with increased cardiac indices, decreased systemic vascular resistance indices, impaired oxygenation, and increased pulmonary shunt fractions. In both groups, oxygen delivery was significantly increased, while oxygen consumption remained virtually unchanged, resulting in a decreased oxygen extraction ratio. In the control group, the significant alterations in systemic hemodynamics, lung function and oxygen transport persisted for the remainder of the study. Administration of N omega-nitro-L-arginine methyl ester normalized cardiac index and systemic vascular resistance index, increased mean arterial blood pressure, and decreased heart rate. Although oxygen delivery significantly decreased after administration of N omega-nitro-L-arginine methyl ester, oxygen consumption did not change, resulting in a normalization of oxygen extraction ratio. Despite a significant reduction of pulmonary shunt fraction, oxygenation dig not improve. Pulmonary arterial pressure and pulmonary vascular resistance index showed a peak 2 hrs after administration of the nitric oxide synthesis inhibitor and then tended to decrease. In contrast, the effects of N omega-nitro-L-arginine methyl ester on the systemic circulation persisted for the remainder of the study. Conclusions: The data support the assumption that augmented nitric oxide production is a major cause of the hemodynamic alterations seen in hyperdynamic endotoxemia. Administration of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester normalized the endotoxin-induced hyperdynamic state, but did not impair oxygen consumption, indicating adequate tissue perfusion of metabolically active organs. Inhibition of nitric oxide synthesis may be a therapeutic option in the treatment of hyperdynamic septic patients when conventional therapy fails to maintain a minimum of cardiovascular performance.