Reinforcement Therapy Using Nitric Oxide Synthase Inhibitors Against Endotoxin Shock in Dogs
Reinforcement Therapy Using Nitric Oxide Synthase Inhibitors Against Endotoxin Shock in Dogs
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DOI：
10.1007/s00595-006-3248-z
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发表时间：
2006-09
期刊：
影响因子：
2.5
通讯作者：
H. Suga;T. Nakagawa;Y. Soga;Yoshizumi Deguchi;Tadashi Suzuki;N. Miyoshi;Y. Imamura;M. Fukuda
中科院分区：
文献类型：
--
作者：
H. Suga;T. Nakagawa;Y. Soga;Yoshizumi Deguchi;Tadashi Suzuki;N. Miyoshi;Y. Imamura;M. Fukuda
目的一氧化氮合酶（NOS）抑制剂被证实可以纠正与感染性休克相关的低血压，但总体预后往往悲观。组织学检查结果未显示任何改善。事实上，一些患者甚至表现出病情恶化的迹象。本研究的目的是探讨 NOS 抑制剂和儿茶酚胺对患有内毒素休克的犬的治疗效果。还评估了这些药物产生的组织学变化。方法在咪达唑仑麻醉下使用杂种狗。股动脉置入PiCCO连续心输出量监测导管，颈外动脉置入中心静脉监测导管。结果给予内毒素（0.5mg/kg，静脉注射）引起休克。观察到这种休克状态后，NOS 抑制剂和儿茶酚胺会升高血压，并且发现去甲肾上腺素（NA，2mg/kg/h）比 S-甲基异硫脲（SMT，20mg/kg/h）更有效。 SMT-NA 或 SMT-DOB 的联合作用大于单独使用 NA 或多巴酚丁胺 (DOB) 的作用。内毒素休克引起的组织学变化并没有因NOS抑制剂的使用而得到改善，反而似乎有所加剧。结论NOS抑制剂联合儿茶酚胺可以减少感染性休克患者的儿茶酚胺剂量；因此它们被认为是血液动力学上有效的药物。
PurposeNitric oxide synthase (NOS) inhibitors were confirmed to correct the hypotension associated with septic shock, but the overall prognosis is often pessimistic. The histological findings failed to show any improvement. In fact, some patients even exhibited signs of exacerbation. The purpose of this study was to investigate the therapeutic effects of NOS inhibitors and catecholamines in dogs suffering from endotoxin shock. The histological changes produced by these agents were also evaluated.MethodsMongrel dogs were used under midazolam anesthesia. A PiCCO continuous cardiac output monitoring catheter was placed in the femoral artery, and a central venous monitoring catheter was placed in the external carotid artery.ResultsEndotoxin (0.5 mg/kg, i.v.) was administered to cause shock. After this shock state was observed, the NOS inhibitors and catecholamines raised the blood pressure, and norepinephrine (NA, 2 mg/kg/h) was found to be more potent thanS-methylisothiourea (SMT, 20 mg/kg/h). The combined effects of SMT-NA or SMT-DOB were greater than those of NA or dobutamine (DOB) alone. The histological changes induced by endotoxin shock were not ameliorated by the administration of NOS inhibitors but instead appeared to be exacerbated to some degree.ConclusionNOS inhibitors combined with cathecholamines were thus suggested to be able to reduce the cathecolamine dosage in patients suffering from septic shock; They are thus considered to be hemodynamically effective agents.