PREVENTIVE EFFECTS OF INDOMETHACIN ON DIAPHRAGMATIC CONTRACTILE ALTERATIONS IN ENDOTOXEMIC RATS
PREVENTIVE EFFECTS OF INDOMETHACIN ON DIAPHRAGMATIC CONTRACTILE ALTERATIONS IN ENDOTOXEMIC RATS
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DOI：
10.1164/ajrccm/142.1.193
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发表时间：
1990-07-01
期刊：
影响因子：
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通讯作者：
AUBIER, M
中科院分区：
文献类型：
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作者：
BOCZKOWSKI, J;DUREUIL, B;AUBIER, M
我们评估了亚致死性大肠杆菌内毒素血症与吲哚美辛伴随给药和不伴随给药对体内大鼠模型的抗凝血强度的影响。96只大鼠连续两天皮下接种0.3和0.6 mg/100 g体重的E.大肠杆菌脂多糖组（E组，n = 64），生理盐水组（C组，n = 32）。将E组动物分为两组，分别皮下注射内毒素组（E组，n = 32）和内毒素加吲哚美辛组（EI组，n = 32）。在第一次内毒素或生理盐水给药后2天，评价每组14只动物的膈肌强度。通过在不同频率（0.5、10、20、30、50和100 Hz）下电刺激膈神经期间测量跨膜压（Pdi）来评估膈肌强度。每天在首次给予内毒素或生理盐水后1天和2天，对每组9只动物进行肺组织学检查和肺重量测量。在内毒素接种动物的肺中观察到中性粒细胞数量轻微增加，但无肺泡间隔增厚和肺泡水肿。C、E和EI组之间的肺重量/体重比和肺干/湿重量比均无差异。膈肌重量在三组中没有差异，而伸趾长肌、胫骨前肌和比目鱼肌的重量在E中与C和EI动物相比显著降低。与C组相比，E组膈肌强度降低，定义为50和100 Hz时Pdi降低。E组动物的肌力降低与抽搐PdI（雌性）的松弛速率增加有关。与C组动物相比（E：18.08 ±. 1.02 MS; C：14.41 ±。0.81 ms; p < 0.05）。吲哚美辛给药期间内毒素血症防止减少Pdi在50和100 Hz和延长。(EI：15.35 .+-. 0.7 ms;与E相比p < 0.05）。我们的结论是：（1）大鼠亚致死性内毒素血症导致继发于收缩力受损的强直性肌张力降低，（2）吲哚美辛给药可预防这一现象，表明这可能是由花生四烯酸前列腺素系统的产物介导的。
We evaluated the effects of a sublethal Escherichia coli endotoxemia with and without concomitant administration of indomethacin on diaphragmatic strength in an in vivo rat model. Ninety-six rats were inoculated subcutaneously on two successive days with 0.3 and 0.6 mg/100 g body weight of E. coli lipopolysaccharide, respectively (E animals, n = 64), or saline (C group, n = 32). E animals were divided into two groups based on subcutaneous administration of endotoxin alone (E group, n = 32) or endotoxin plus indomethacin (2.5 mg/kg body weight/day) (EI group, n = 32). Diaphragmatic strength was evaluated in 14 animals from each group 2 days after the first endotoxin or saline administration. Diaphragmatic strength was assessed by measuring the transdiaphragmatic pressure (Pdi) during electrical stimulation of the phrenic nerves at different frequencies (0.5, 10, 20, 30, 50, and 100 Hz). Lung histologic examination and measurements of lung weights were performed 1 and 2 days after the first endotoxin or saline administration in nine animals of each group each day. A slight increase in the number of neutrophils without alveolar septal thickening and alveolar edema was observed in the lungs of endotoxin-inoculated animals. No differences in the lung weight to body weight ratio nor in the dry to wet weight ratio of the lungs were noted between C, E, and EI groups. Diaphragmatic weight was not different in the three groups, whereas the weights of the extensor digitorium longus, tibialis anterior, and soleus muscles were significantly reduced in E compared with C and EI animals. Diaphragmatic strength was reduced in Group E when compared with group C as defined by reduction in Pdi for 50 and 100 Hz. Reduced diaphragmatic strength in E animals was associated with an increase in the rate of relaxation of the twitch PdI (.female.) when compared with C animals (E: 18.08 .+-. 1.02 ms; C: 14.41 .+-. 0.81 ms; p < 0.05). Indomethacin administration during endotoxemia prevented both the reduction in Pdi at 50 and 100 Hz and prolongation in .female. (EI: 15.35 .+-. 0.7 ms; p < 0.05 compared with E). We conclude that (1) sublethal endotoxemia in rats produces a decrease in tetanic diaphragmatic strength secondary to an impaired contractility, and (2) prevention of this phenomenon by indomethacin administration suggests that it could be mediated by products of the arachidonic acid prostaglandin system.