PROTECTIVE EFFECTS OF N-ACETYL-L-CYSTEINE IN ENDOTOXEMIA

被引:133
|
作者
ZHANG, HB
SPAPEN, H
NGUYEN, DN
BENLABED, M
BUURMAN, WA
VINCENT, JL
机构
[1] ERASME UNIV HOSP, DEPT INTENS CARE, B-1070 BRUSSELS, BELGIUM
[2] UNIV LIMBURG, DEPT SURG, IMMUNOL LAB, 6200 MD MAASTRICHT, NETHERLANDS
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1994年 / 266卷 / 05期
关键词
OXYGEN DELIVERY; OXYGEN EXTRACTION; OXYGEN FREE RADICALS; GLUTATHIONE PEROZIDASE; PEROXIDASE; SUPEROXIDE DISMUTASE; VITAMIN-E; TUMOR NECROSIS FACTOR; TAMPONADE; HYPOXIA;
D O I
10.1152/ajpheart.1994.266.5.H1746
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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,it 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. In this model of endotoxic shock, prior administration of NAC improved oxygen extraction capabilities as well as myocardial function. Enhancement of glutathione peroxidase activity and inhibition of TNF release by NAC can be implicated.
引用
收藏
页码:H1746 / H1754
页数:9
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