Nishikawa Y, Mathison J, Lew W Y
Department of Medicine, Department of Veterans Affairs Medical Center, San Diego, California, USA.
Am J Physiol. 1996 Feb;270(2 Pt 2):H485-91. doi: 10.1152/ajpheart.1996.270.2.H485.
Tumor necrosis factor-alpha (TNF-alpha) is an endogenous mediator for several effects of endotoxin. To evaluate whether TNF-alpha mediates endotoxin-induced left ventricular (LV) dysfunction, we measured LV function (sonomicrometers) and serum TNF-alpha (cytolytic assay) in anesthetized rabbits given endotoxin (100 micrograms/kg iv). In the control group (n = 8), systolic depression (defined by a > 10% increase in end-systolic volume at a matched end-systolic pressure) developed in four rabbits and diastolic dilation (> 10% increase in end-diastolic volume at a matched end-diastolic pressure) developed in three rabbits. Neither the increase in end-systolic volume nor the increase in end-diastolic volume correlated with the increase in TNF-alpha, which reached a peak of 2,875 +/- 762 U/ml. In a second group of rabbits (n = 7), a goat polyclonal anti-rabbit antibody to TNF-alpha was given 30-60 min before endotoxin. Anti-TNF-alpha antibody alone did not alter LV function. Although the TNF-alpha response to endotoxin was effectively blunted (peak TNF-alpha remained < 100 U/ml), all seven rabbits developed systolic depression (P = 0.08 compared with control group) and diastolic dilation (P = 0.03). We conclude that serum TNF-alpha does not mediate endotoxin-induced LV systolic depression or diastolic dilation in this model.
肿瘤坏死因子-α（TNF-α）是内毒素多种效应的内源性介质。为评估TNF-α是否介导内毒素诱导的左心室（LV）功能障碍，我们在静脉注射内毒素（100微克/千克）的麻醉兔中测量了LV功能（超声微测仪）和血清TNF-α（细胞溶解测定法）。在对照组（n = 8）中，4只兔出现收缩期抑制（定义为在匹配的收缩末期压力下收缩末期容积增加> 10%），3只兔出现舒张期扩张（在匹配的舒张末期压力下舒张末期容积增加> 10%）。收缩末期容积增加和舒张末期容积增加均与TNF-α升高无关，TNF-α升高至峰值2,875 +/- 762 U/ml。在第二组兔（n = 7）中，在内毒素注射前30 - 60分钟给予山羊抗兔TNF-α多克隆抗体。单独的抗TNF-α抗体未改变LV功能。尽管对内毒素的TNF-α反应有效减弱（TNF-α峰值仍< 100 U/ml），但所有7只兔均出现收缩期抑制（与对照组相比P = 0.08）和舒张期扩张（P = 0.03）。我们得出结论，在该模型中血清TNF-α不介导内毒素诱导的LV收缩期抑制或舒张期扩张。
