Girardin E, Grau G E, Paunier L, Le Coultre C
Department of Pediatrics, Hôpital des Enfants, Geneva, Switzerland.
Circ Shock. 1994 Jan;42(1):20-6.
TNF alpha is an early mediator of endotoxemic shock. Its acute effect on renal hemodynamics is not known. In this study, the early hemodynamic and renal effects of TNF alpha were investigated in a rabbit model of shock, in which the measurement of the aortic blood flow before the bifurcation of the renal arteries allows one to differentiate between prerenal factors and hemodynamic renal response. Six groups of rabbits were studied, receiving either: (1) endotoxin, (2) endotoxin + thromboxane inhibitor Dazmegrel, (3) TNF alpha, (4) TNF alpha + Dazmegrel, (5) TNF alpha+indomethacin, or (6) placebo. Between 60 min and 3 hr after the injection, endotoxin induced a mean fall in arterial pressure of 32% (P < 0.01) and TNF alpha of 16% (P < 0.01). After endotoxin, the aortic blood flow decreased by 27% (P < 0.01) and after TNF alpha by 18% (P < 0.001). Both specific thromboxane inhibition and indomethacin abolished the TNF alpha central hemodynamic effect. The renal blood flow (-53%), the renal fraction of the aortic blood flow (-38%), and the glomerular filtration rate (-47%, P < 0.05) decreased 1 hr after endotoxin injection. In contrast, TNF alpha induced only a slight fall of the renal fraction of the aortic blood flow (-19%) after 2.5 hr. Glomerular filtration was not modified after TNF alpha injection most likely because of a 17% mean increase of filtration fraction in this group (P < 0.001). These data indicate that TNF alpha is implicated in the early hemodynamic changes of endotoxemic shock.(ABSTRACT TRUNCATED AT 250 WORDS)
肿瘤坏死因子α（TNFα）是内毒素血症性休克的早期介质。其对肾血流动力学的急性作用尚不清楚。在本研究中，在休克兔模型中研究了TNFα的早期血流动力学和肾脏效应，其中通过测量肾动脉分叉前的主动脉血流量，可区分肾前因素和肾脏血流动力学反应。研究了六组兔子，分别给予：（1）内毒素，（2）内毒素+血栓素抑制剂达美格雷，（3）TNFα，（4）TNFα+达美格雷，（5）TNFα+吲哚美辛，或（6）安慰剂。注射后60分钟至3小时内，内毒素导致平均动脉压下降32%（P<0.01），TNFα导致下降16%（P<0.01）。内毒素注射后，主动脉血流量下降27%（P<0.01），TNFα注射后下降18%（P<0.001）。特异性血栓素抑制和吲哚美辛均消除了TNFα的中心血流动力学效应。内毒素注射1小时后，肾血流量（-53%）、主动脉血流量的肾部分（-38%）和肾小球滤过率（-47%，P<0.05）下降。相比之下，TNFα注射2.5小时后仅导致主动脉血流量的肾部分略有下降（-19%）。TNFα注射后肾小球滤过未改变，很可能是因为该组滤过分数平均增加了17%（P<0.001）。这些数据表明，TNFα与内毒素血症性休克的早期血流动力学变化有关。（摘要截断于250字）
