Role of inducible nitric oxide synthase in the reduced responsiveness of the myocardium to catecholamines in a hyperdynamic, murine model of septic shock
Role of inducible nitric oxide synthase in the reduced responsiveness of the myocardium to catecholamines in a hyperdynamic, murine model of septic shock
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DOI：
10.1097/01.ccm.0000199070.46812.21
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发表时间：
2006-02-01
影响因子：
8.8
通讯作者：
Albuszies, G
中科院分区：
文献类型：
--
作者：
Barth, E;Radermacher, P;Albuszies, G
目标.过量的一氧化氮产生是感染性休克低血压和儿茶酚胺抵抗的关键介质。虽然一氧化氮合酶阻断剂已被证明可以恢复血流动力学，但对心肌功能的研究结果相互矛盾。诱导型一氧化氮合酶（iNOS）基因敲除（iNOS-/-）小鼠显示心脏功能改善，但这些结果是在以心输出量减少为特征的低动力休克期间获得的。因此，我们研究了心脏功能和儿茶酚胺反应在临床相关的，盲肠结扎和穿刺（CLP）诱导的脓毒性shock.Design小鼠模型：前瞻性，对照，随机动物研究。大学动物研究实验室。干预：CLP后15小时，将三组小鼠（野生型对照，n = 9; iNOS-/-，n = 12;和在mg.kgCLP后立即腹膜内接受5%www.example.com（-1）选择性iNOS抑制剂GW 274150的野生型小鼠，n = 8）麻醉，机械通气，和仪器（中心静脉和左心室压力传导导管）。在CLP后18、21和24小时记录测量值。羟乙基淀粉和去甲肾上腺素注入，以实现血压正常和高动力学的血流动力学。测量和主要结果：平均动脉压，每搏输出量，左心室射血分数没有组间差异。在GW 274150中，达到血流动力学目标所需的去甲肾上腺素剂量较低（p
Objectives. Excess nitric oxide production is a key mediator of hypotension and catecholamine-resistance in septic shock. Although nitric oxide synthase blockade has been shown to restore hemodynamics, conflicting results on myocardial function were reported. Inducible nitric oxide synthase (iNOS) knockout (iNOS-/-) mice showed improved heart function, but these results were obtained during hypodynamic shock characterized by reduced cardiac output. Therefore, we investigated heart function and catecholamine responsiveness in a clinically relevant, murine model of cecal ligation and puncture (CLP)-induced septic shock.Design: Prospective, controlled, randomized animal study.Setting. University animal research laboratory.Subjects. Male C57BI/6 wild-type and iNOS-/- mice.Interventions: Fifteen hours after CLP, three groups of mice (wild-type controls, n = 9; iNOS-/-, n = 12; and wild-type mice receiving 5 mg.kg(-1) intraperitoneally of the selective iNOS inhibitor GW274150 immediately after CLP, n = 8) were anesthetized, mechanically ventilated, and instrumented (central venous and left ventricular pressure-conductance catheter). Measurements were recorded 18, 21, and 24 hrs post-CLP. Hydroxyethylstarch and norepinephrine were infused to achieve normotensive and hyperdynamic hemodynamics.Measurements and Main Results: There was no intergroup difference in mean arterial pressure, stroke volume, and left ventricular ejection fraction. Norepinephrine doses required to achieve the hemodynamic targets were lower in GW274150 (p