Nitric oxide synthase inhibition versus norepinephrine for the treatment of hyperdynamic sepsis in sheep
Nitric oxide synthase inhibition versus norepinephrine for the treatment of hyperdynamic sepsis in sheep
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DOI：
10.1097/00003246-199605000-00018
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发表时间：
1996-05-01
影响因子：
8.8
通讯作者：
Traber, DL
中科院分区：
文献类型：
--
作者：
Booke, M;Hinder, F;Traber, DL
目的：研究一氧化氮合成抑制剂N-ω-单甲基-L-精氨酸（L-NMMA）对高动力性脓毒症绵羊模型的血流动力学、氧转运和局部血流量的影响，并将这些影响与去甲肾上腺素的反应进行比较。设计：前瞻性、非随机、重复测量的对照实验研究。二十五名女性，健康，成年羊的美利奴品种，分为三组：9个对照羊; 8只羊用L-NMMA治疗;和8只羊用去甲肾上腺素治疗。5天恢复期后，开始连续输注活铜绿假单胞菌（2.5 x 10（6）菌落形成单位/min），并在实验的剩余时间内维持。脓毒症24小时后，8只绵羊接受L-NMMA（7 mg/kg/hr），8只绵羊接受去甲肾上腺素，9只绵羊接受单独的溶媒（0.9%盐水）。去甲肾上腺素的剂量是连续和单独调整，以实现相同的增加，在血压中观察到在匹配的羊的L-NMMA group.Measurements和主要结果：24小时的脓毒症后，所有的羊发展高动力循环状态，增加心脏指数和降低动脉压，和全身血管阻力。L-NMMA逆转高动力循环，通过外周血管收缩引起动脉压升高。去甲肾上腺素通过增加心脏指数导致血压升高，而全身血管阻力不受影响。维持高血压所需的去甲肾上腺素剂量必须持续增加，这反映了脓毒症期间血管对儿茶酚胺的反应性降低。肾血流量不受所有治疗形式的影响。去甲肾上腺素和L-NMMA导致尿量急剧增加。阻断一氧化氮合酶与L-NMMA没有干扰宿主的肺部清除细菌的能力，也没有治疗与去甲肾上腺素。结论：阻断一氧化氮合酶有显着的血管收缩作用。去甲肾上腺素和L-NMMA都增加了动脉压，而不减少肾血流量，导致肾功能改善。
Objectives: To investigate the effects of N-omega-mono-methyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, on hemodynamics, oxygen transport, and regional blood flow in an ovine model of hyperdynamic sepsis and to compare these effects with the responses to norepinephrine.Design: Prospective, nonrandomized, controlled experimental study with repeated measures.Setting: Investigational intensive care unit at a university medical center.Subjects: Twenty-five female, healthy, adult sheep of the Merino breed, divided into three groups: nine control sheep; eight sheep treated with L-NMMA; and eight sheep treated with norepinephrine.Interventions: All sheep were chronically instrumented. After a 5-day recovery period, a continuous infusion of live Pseudomonas aeruginosa (2.5 x 10(6) colony forming units/min) was started and maintained for the remainder of the experiment. After 24 hrs of sepsis, eight sheep received L-NMMA (7 mg/kg/hr), eight sheep received norepinephrine, and nine sheep received the vehicle alone (0.9% saline). The norepinephrine dosage was continuously and individually adjusted to achieve the same increase in blood pressure as was observed in a matched sheep of the L-NMMA group.Measurements and Main Results: After 24 hrs of sepsis, all sheep developed a hyperdynamic circulatory state with increased cardiac indices and reduced arterial pressures, and systemic vascular resistances. L-NMMA reversed the hyperdynamic circulation, causing an increase in arterial pressure by peripheral vasoconstriction. Norepinephrine led to an increase in blood pressure by augmenting cardiac indices, leaving the systemic vascular resistance unaffected. The norepinephrine dose needed to keep the blood pressure high had to be continuously increased, reflecting the reduced vascular responsiveness to catecholamines during sepsis. Renal blood flow remained unaffected by all treatment forms. Norepinephrine and L-NMMA led to a dramatic increase in urine production. Blocking the nitric oxide synthase with L-NMMA did not interfere with the host's pulmonary ability to clear bacteria, nor did treatment with norepinephrine.Conclusions: Blocking nitric oxide synthase had a marked vasoconstrictive effect. Both norepinephrine and L-NMMA increased arterial pressure without reducing renal blood flow, leading to an improved renal function.