Effects of hyperchloremic acidosis on arterial pressure and circulating inflammatory molecules in experimental sepsis

Effects of hyperchloremic acidosis on arterial pressure and circulating inflammatory molecules in experimental sepsis
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DOI:
10.1378/chest.125.1.243
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发表时间:
2004-01-01
期刊:
影响因子:
9.6
通讯作者:
Venkataraman, R
Venkataraman, R
中科院分区:
医学1区
文献类型:
--
作者:
Kellum, JA;Song, MC;Venkataraman, R

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研究目的:建立严重脓毒症大鼠实验模型,探讨稀释盐酸诱导的高氯血症性酸中毒对大鼠血压和循环炎症介质的影响。设计:随机、开放标签、对照实验。环境:大学研究实验室。参与者:24只成年雄性Sprague-Dawley鼠。干预:采用盲肠结扎穿刺诱导致死性脓毒症18 h后,随机分为3组。在第2组和第3组,我们开始静脉输注0.1 N HCl,以分别降低5至10 mEq/L和10至15 mEq/L的标准碱过量(SBE)。在第一组,我们输注相同体积的乳酸林格氏液。在两组中,持续注射8小时或直至动物死亡。测量:测量平均动脉压(MAP),动脉血液气体,电解质,等离子体硝酸盐或亚硝酸盐,肿瘤坏死因子(TNF) t1,白介素6 (IL),和IL - 10水平在0 h, 3 h, 6 h,和8 h.Results:地图保持稳定我但减少组2和3组(p < 0.001),这样在组1 8 h地图要高得多(94 + / - 9.2修女Hg) (+ / - SD)相比,两组2(71.6 + / - 20.1毫米汞柱)或一组3(49.4 + / - 33.2毫米汞柱)(p = 0.01)。MAP的变化与血浆Cl-升高相关(R-2 = 0.50, p < 0.0001),与pH降低相关性较弱(R-2 = 0.24, p < 0.001)。酸中毒6 h后,2组动物血浆亚硝酸盐水平显著高于1组和3组(p < 0.05)。血浆tnf - α、IL-6或IL-10水平与对照动物无显著差异。结论:HCl输注引起的脓毒症大鼠中度酸中毒(SBE为5 ~ 10 mEq/L),使血压恶化,血浆硝酸盐/亚硝酸盐水平升高,但对循环细胞因子无影响。然而,严重的酸中毒(SBE为10 - 15 mEq/L)虽然仍引起低血压,但不影响血浆硝酸盐/亚硝酸盐水平。
Study objective: To determine the effects of hyperchloremic acidosis, induced by dilute HCl infusion, on BP and circulating inflammatory mediators in an experimental model of severe sepsis in the rat.Design: Randomized, open-label, controlled experiment.Setting: University research laboratory.Participants: Twenty-four adult, male, Sprague-Dawley rats.Intervention: Eighteen hours after inducing lethal sepsis by cecal ligation and puncture, animals were randomized and classified into three groups. In groups 2 and 3, we began an IV infusion of 0.1 N HCl to reduce the standard base excess (SBE) by 5 to 10 mEq/L and 10 to 15 mEq/]L, respectively. In group 1, we infused a similar volume of lactated Ringer solution. in an groups, infusions were continued for 8 h or until the animals died.Measurements: We measured mean arterial pressure (MAP), arterial blood gases, electrolytes, plasma nitrate/nitrite, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 levels at 0 h, 3 h, 6 h, and 8 h.Results: MAP remained stable in group I but decreased in groups 2 and 3 (p < 0.001), such that at 8 h MAP was much higher in group 1 (94 +/- 9.2 nun Hg) [ +/- SD] compared to either group 2 (71.6 +/- 20.1 mm Hg) or group 3 (49.4 +/- 33.2 mm Hg) [p = 0.01]. This change in MAP correlated with the increase in plasma Cl- (R-2 = 0.50, p < 0.0001) and less well with the decrease in pH (R-2 = 0.24, p < 0.001). After. 6 h of acidosis, plasma nitrite levels were significantly higher in group 2 animals compared to either group 1 or group 3 animals (p < 0.05). Plasma TNF-alpha, IL-6, or IL-10 levels were not significantly different from control animals.Conclusion: Moderate acidosis (SBE of 5 to 10 mEq/L), induced by HCl infusion, worsened BP and increased plasma nitrate/nitrite levels but had no effect on circulating cytokines in septic rats. However, severe acidosis (SBE of 10 to 15 mEq/L), while still causing hypotension, did not affect plasma nitrate/nitrite levels.