Anticoagulants influence the in vitro activity and composition of shock lymph but not its in vivo activity.
Anticoagulants influence the in vitro activity and composition of shock lymph but not its in vivo activity.
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DOI：
10.1097/shk.0b013e3182205c30
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Feinman R
中科院分区：
文献类型：
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作者：
Deitch EA;Qin X;Sheth SU;Tiesi G;Palange D;Dong W;Lu Q;Xu D;Feketeova E;Feinman R
创伤失血性休克(T/HS)的许多模型都需要回输抗凝的失血。我们最近观察到抗凝剂肝素诱导肠系膜淋巴脂肪酶活性升高，从而导致体外内皮细胞毒性，促使我们研究肝素诱导的脂肪酶活性在体内器官损伤中的作用以及其他抗凝剂在体外和体内对肠系膜淋巴生物活性的影响。为了研究这一问题，对创伤出血大鼠的失血用肝素、合成抗凝剂Arixtra或柠檬酸盐进行抗凝。与肝素相比，Arixtra不会增加淋巴脂肪酶活性，也不会导致高水平的内皮细胞毒性。但阿利施特拉组T/HS大鼠仍存在肺损伤、中性粒细胞启动和红细胞功能障碍，但经淋巴管结扎后完全消失。此外，将从Arixtra大鼠采集的T/HS肠系膜淋巴(而不是假休克淋巴)注入对照组小鼠，再现了真正休克后观察到的肺损伤、PMN激活和红细胞功能障碍的模式。与这些观察结果一致的是，柠檬酸抗凝的T/HS大鼠发生了肺损伤，而将柠檬酸抗凝的T/HS大鼠的肠系膜淋巴注射到对照组小鼠也导致了肺损伤。基于这些结果，可以得出几个结论。首先，肝素诱导的肠系膜淋巴脂肪酶活性升高不是T/HS肠系膜淋巴体内效应的原因。其次，在研究肠系膜淋巴的生物学或成分时，应避免使用肝素作为抗凝剂，因为它能够引起淋巴脂肪酶活性的增加，从而增加这些淋巴样本的体外细胞毒性。
Many models of trauma-hemorrhagic shock (T/HS) involve the reinfusion of anticoagulated shed blood. Our recent observation that the anticoagulant heparin induces increased mesenteric lymph lipase activity and consequent in vitro endothelial cell cytotoxicity prompted us to investigate the effect of heparin-induced lipase activity on organ injury in vivo as well as the effects of other anticoagulants on mesenteric lymph bioactivity in vitro and in vivo. To investigate this issue, rats subjected to trauma-hemorrhage had their shed blood anticoagulated with heparin, the synthetic anticoagulant arixtra or citrate. Arixtra, in contrast to heparin, did not increased lymph lipase activity or result in high levels of endothelial cytotoxicity. Yet, the arixtra-treated rats subjected to T/HS still manifested lung injury, neutrophil priming and RBC dysfunction, which was totally abrogated by lymph duct ligation. Furthermore, the injection of T/HS mesenteric lymph, but not sham-shock lymph, collected from the arixtra rats into control mice recreated the pattern of lung injury, PMN priming and RBC dysfunction observed after actual shock. Consistent with these observations, citrate anticoagulated rats subjected to T/HS developed lung injury and the injection of mesenteric lymph from the citrate-anticoagulated T/HS rats into control mice also resulted in lung injury. Based on these results, several conclusions can be drawn. First, heparin-induced increased mesenteric lymph lipase activity is not responsible for the in vivo effects of T/HS mesenteric lymph. Secondly, heparin should be avoided as an anticoagulant when studying the biology or composition of mesenteric lymph due to its ability to cause increases in lymph lipase activity that increase the in vitro cytotoxicity of these lymph samples.