ANTITUMOR NECROSIS FACTOR-ALPHA PREVENTS DECREASED VENTRICULAR CONTRACTILITY IN ENDOTOXEMIC PIGS
ANTITUMOR NECROSIS FACTOR-ALPHA PREVENTS DECREASED VENTRICULAR CONTRACTILITY IN ENDOTOXEMIC PIGS
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DOI：
10.1164/ajrccm.152.2.7633696
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发表时间：
1995-08-01
影响因子：
24.7
通讯作者：
WALLEY, KR
中科院分区：
文献类型：
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作者：
HERBERTSON, MJ;WERNER, HA;WALLEY, KR
目前尚不清楚内毒素暴露后左心室收缩能力下降是如何介导的，也不知道肿瘤坏死因子-α抗体是否可以预防这种下降。用绵羊抗人肿瘤坏死因子α多克隆抗体(抗肿瘤坏死因子α)、非特异性免疫球蛋白抗体或生理盐水对4组6头麻醉和仪器化的猪进行预处理，然后用内毒素或生理盐水处理。我们测量了血流动力学、左心室压力(Millar导管)和容量(电导导管)。使用收缩末期压力-容量关系的斜率(E(Max))评估左心室收缩能力。内毒素注射4h后，非特异性免疫球蛋白预处理组E(Max)下降44+/-6%(p<；0.05)，平均动脉压从115+/-7 mm Hg降至70+/-10 mm Hg(p<；0.05)，心输出量在开始升高后迅速下降(p<；0.05)。抗肿瘤坏死因子α显著降低4h的E(Max)(11+/-9%，p<；0.05)和全身性低血压(108+/-15 mm Hg至99+/-6 mm Hg，p<；0.05)，并阻止晚期心输出量的下降。这提示，肿瘤坏死因子α是脓毒症导致左心室收缩能力下降的重要早期介质。
It is not known how the decrease in left ventricular contractility following endotoxin exposure is mediated, or whether this decrease is preventable by antibodies to tumor necrosis factor-alpha (TNF alpha). Four groups of six anesthetized and instrumented pigs were pretreated with ovine polyclonal antibody to human TNF alpha (anti-TNF alpha), nonspecific IgG, or saline, and then treated with either endotoxin or saline. We measured hemodynamics and left ventricular pressures (Millar catheter) and volumes (conductance catheter). Left ventricular contractility was assessed using the slope (E(max)) of the end-systolic pressure-volume relationship. Four hours after the start of endotoxin infusion In the nonspecific IgG pretreated group, E(max) had decreased by 44 +/- 6% (p < 0.05), mean arterial pressure had decreased from 115 +/- 7 mm Hg to 70 +/- 10 mm Hg (p < 0.05), and cardiac output was rapidly decreasing after an initial increase (p < 0.05). Anti-TNF alpha significantly reduced the decrease in E(max) (11 +/- 9%, p < 0.05), and the systemic hypotension (108 +/- 15 mm Hg to 99 +/- 6 mm Hg, p < 0.05), at 4 h, and prevented the late decrease in cardiac output. This suggests that TNF alpha is an important early mediator in sepsis leading to decreased left ventricular contractility.