TNF-α and myocardial depression in endotoxemic rats:: Temporal discordance of an obligatory relationship
TNF-α and myocardial depression in endotoxemic rats:: Temporal discordance of an obligatory relationship
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DOI：
10.1152/ajpregu.1998.275.2.r502
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发表时间：
1998-08-01
影响因子：
2.8
通讯作者：
Harken, AH
中科院分区：
文献类型：
--
作者：
Meng, XZ;Ao, LH;Harken, AH
外源性肿瘤坏死因子-α（TNF-α）在体内诱导延迟性心肌抑制，但在体外促进快速心肌抑制。内源性TNF-α和内毒素性心肌抑制之间的时间关系尚不清楚，TNF-α在这种心肌疾病中的作用仍有争议。使用未并发休克的内毒素血症大鼠模型，我们试图确定1）循环和心肌TNF-α变化与心肌抑制的时间关系，2）蛋白质合成抑制或免疫抑制对TNF-α产生和心肌抑制的影响，以及3）TNF-α中和对心肌抑制的影响。用脂多糖（LPS，0.5mg/kg ip）处理大鼠。循环和心肌TNF-α在1和2小时增加，而心肌收缩力在4和6小时被抑制。用放线菌酮或地塞米松预处理可消除循环和心肌TNF-α的增加，并保留心肌收缩功能。同样地，在LPS后立即用TNF结合蛋白治疗可防止心肌抑制。我们的结论是内源性TNF-α介导内毒素血症大鼠迟发性心肌抑制，抑制TNF-α的产生或中和TNF-α可保护内毒素血症心肌收缩功能。
Exogenous tumor necrosis factor-alpha (TNF-alpha) induces delayed myocardial depression in vivo but promotes rapid myocardial depression in vitro. The temporal relationship between endogenous TNF-alpha and endotoxemic myocardial depression is unclear, and the role of TNF-alpha in this myocardial disorder remains controversial. Using a rat model of endotoxemia not complicated by shock, we sought to determine 1) the temporal relationship of changes in circulating and myocardial TNF-alpha with myocardial depression, 2) the influences of protein synthesis inhibition or immunosuppression on TNF-alpha production and myocardial depression, and 3) the influence of neutralization of TNF-alpha on myocardial depression. Rats were treated with lipopolysaccharide (LPS, 0.5 mg/kg ip). Circulating and myocardial TNF-alpha increased at 1 and 2 h, whereas myocardial contractility was depressed at 4 and 6 h. Pretreatment with cycloheximide or dexamethasone abolished the increase in circulating and myocardial TNF-alpha and preserved myocardial contractile function. Similarly, treatment with TNF binding protein immediately after LPS prevented myocardial depression. We conclude that endogenous TNF-alpha mediates delayed myocardial depression in endotoxemic rats and that inhibition of TNF-alpha production or neutralization of TNF-alpha preserves myocardial contractile function in endotoxemia.