Zhang H, Spapen H, Nguyen D N, Benlabed M, Buurman W A, Vincent J L
Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium.
Am J Physiol. 1994 May;266(5 Pt 2):H1746-54. doi: 10.1152/ajpheart.1994.266.5.H1746.
Because oxygen free radicals have been implicated in the endothelial cell damage and in the myocardial depression occurring during severe sepsis, we investigated whether N-acetyl-L-cysteine (NAC) could influence the oxygen extraction capabilities during an acute reduction in blood flow induced by cardiac tamponade after endotoxin challenge. Sixteen anesthetized, saline-infused, and ventilated dogs received Escherichia coli endotoxin (2 mg/kg) 30 min before tamponade was induced by repeated bolus injections of warm saline into the pericardial space. Thirty minutes before endotoxin administration, nine dogs received NAC (150 mg/kg, followed by a 20 mg.kg-1.h-1 infusion); the other seven dogs served as a control group. The NAC group maintained higher cardiac index, oxygen delivery (DO2), and left ventricular stroke work index, but lower systemic and pulmonary vascular resistance, than the control group. The oxygen uptake (VO2) levels at critical DO2 (DO2crit) were identical in the two groups. However, DO2crit was significantly lower in the NAC than in the control group (8.1 +/- 1.7 vs. 10.8 +/- 1.8 ml.kg-1.min-1, P < 0.01). Critical oxygen extraction ratio and the slope of the VO2-to-DO2-dependent line were higher in the NAC than in the control group (72 +/- 14 vs. 53 +/- 15% and 0.80 vs. 0.56, respectively; both P < 0.05). The peak lactate and the maximal tumor necrosis factor (TNF) levels were lower in the NAC than in the control group (5.2 +/- 0.4 vs. 7.6 +/- 0.4 mM, and 0.14 +/- 0.03 vs. 1.21 +/- 0.58 ng/ml, respectively; both P < 0.01). NAC significantly increased glutathione peroxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
由于氧自由基与严重脓毒症时发生的内皮细胞损伤及心肌抑制有关，我们研究了N-乙酰-L-半胱氨酸（NAC）是否会在内毒素激发后，心脏压塞引起急性血流减少期间影响氧摄取能力。16只麻醉、输注生理盐水并进行机械通气的犬，在通过向心包腔内反复推注温盐水诱发心脏压塞前30分钟，接受大肠杆菌内毒素（2mg/kg）。在内毒素给药前30分钟，9只犬接受NAC（150mg/kg，随后以20mg·kg-1·h-1输注）；另外7只犬作为对照组。与对照组相比，NAC组维持了更高的心指数、氧输送（DO2）和左心室每搏功指数，但全身和肺血管阻力更低。两组在临界DO2（DO2crit）时的氧摄取（VO2）水平相同。然而，NAC组的DO2crit显著低于对照组（8.1±1.7 vs. 10.8±1.8ml·kg-1·min-1，P<0.01）。NAC组的临界氧摄取率和VO2与DO2依赖线的斜率高于对照组（分别为72±14 vs. 53±15%和0.80 vs. 0.56；P均<0.05）。NAC组的乳酸峰值和最大肿瘤坏死因子（TNF）水平低于对照组（分别为5.2±0.4 vs. 7.6±0.4mM，以及0.14±0.03 vs. 1.21±0.58ng/ml；P均<0.01）。NAC显著提高了谷胱甘肽过氧化物酶活性（摘要截断于250字）
