Hauser Balázs, Kick Jochen, Asfar Pierre, Ehrmann Ulrich, Albicini Maura, Vogt Josef, Wachter Ulrich, Brückner Uwe Bernd, Fink Mitchell P, Radermacher Peter, Bracht Hendrik
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.
Crit Care Med. 2005 Sep;33(9):2034-42. doi: 10.1097/01.ccm.0000178177.03979.ce.
To investigate the systemic, pulmonary, and hepatosplanchnic hemodynamic and metabolic effects of delayed treatment with ethyl pyruvate in a long-term porcine model of hyperdynamic endotoxemia.
Prospective, randomized, controlled experimental study with repeated measures.
Investigational animal laboratory.
Anesthetized, mechanically ventilated, and instrumented pigs.
After 12 hrs of continuous infusion of lipopolysaccharide and hydroxyethyl starch to keep mean arterial pressure >60 mm Hg, swine randomly received placebo (Ringer's solution; control group, n = 11) or ethyl pyruvate in lactated Ringer's solution (n = 8; 0.03 g.kg(-1) loading dose over 10 mins, thereafter 0.03 g.kg(-1)hr(-1) for 12 hrs).
Whereas mean arterial pressure significantly decreased in control animals, mean arterial pressure was maintained at the baseline level in pigs treated with ethyl pyruvate. Global oxygen uptake was comparable, so that the trend toward a higher oxygen transport and the significantly higher mixed venous hemoglobin oxygen saturation resulted in a significantly lower oxygen extraction in the ethyl pyruvate group. Ethyl pyruvate reduced intrapulmonary venous admixture and resulted in significantly greater Pa(O2)/F(IO2) ratios. Despite comparable urine production in the two groups during the first 18 hrs of endotoxemia, ethyl pyruvate significantly increased diuresis during the last 6 hrs of the study. Lipopolysaccharide-induced systemic and regional venous metabolic acidosis was significantly ameliorated by ethyl pyruvate. Endotoxemia increased both blood nitrate + nitrite and isoprostane concentrations, and ethyl pyruvate attenuated the response of these markers of nitric oxide production and lipid peroxidation.
Ethyl pyruvate infusion resulted in improved hemodynamic stability and ameliorated acid-base derangements induced by chronic endotoxemia in pigs. Reduced oxidative stress and an decreased nitric oxide release probably contributed to these effects.
在长期高动力性内毒素血症猪模型中，研究丙酮酸乙酯延迟治疗对全身、肺及肝脾血流动力学和代谢的影响。
前瞻性、随机、对照的重复测量实验研究。
实验动物实验室。
麻醉、机械通气并安装监测仪器的猪。
持续输注脂多糖和羟乙基淀粉12小时以维持平均动脉压>60 mmHg后，猪被随机分为两组，一组接受安慰剂（林格氏液；对照组，n = 11），另一组接受乳酸林格氏液中加入丙酮酸乙酯（n = 8；10分钟内静脉注射负荷剂量0.03 g·kg⁻¹，随后以0.03 g·kg⁻¹·hr⁻¹持续输注12小时）。
对照组动物平均动脉压显著下降，而接受丙酮酸乙酯治疗的猪平均动脉压维持在基线水平。两组的总体氧摄取量相当，因此，丙酮酸乙酯组氧运输量有升高趋势且混合静脉血红蛋白氧饱和度显著更高，导致氧摄取率显著降低。丙酮酸乙酯减少了肺内静脉血掺杂，使动脉血氧分压/吸入氧分数值（Pa(O2)/F(IO2)）显著升高。尽管在内毒素血症的前18小时两组尿量相当，但在研究的最后6小时，丙酮酸乙酯显著增加了尿量。脂多糖诱导的全身和局部静脉代谢性酸中毒被丙酮酸乙酯显著改善。内毒素血症使血中硝酸盐+亚硝酸盐和异前列腺素浓度均升高，丙酮酸乙酯减弱了这些一氧化氮生成和脂质过氧化标志物的反应。
输注丙酮酸乙酯可改善猪慢性内毒素血症所致的血流动力学稳定性并减轻酸碱紊乱。氧化应激减轻和一氧化氮释放减少可能促成了这些效应。
Zotero 插件