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脂质体包裹血红蛋白对大鼠内毒素诱导休克发展的影响。

Effect of liposome-encapsulated hemoglobin on the development of endotoxin-induced shock in the rat.

作者信息

Whiteford M, Spirig A, Rudolph A, Neville L, Abdullah F, Feuerstein G, Rabinovici R

机构信息

Department of Surgery, Jefferson Medical College, Philadelphia, Pennsylvania, USA.

出版信息

Shock. 1998 Jun;9(6):428-33. doi: 10.1097/00024382-199806000-00007.

Abstract

Liposome-encapsulated hemoglobin (LEH) is an experimental oxygen-carrying resuscitation fluid. Because LEH is cleared from the circulation primarily by the reticuloendothelial system, its effect on the development of sepsis remains a major concern. Thus, the present study aimed to evaluate whether LEH modifies consequences of endotoxemia in the conscious normovolemic rat. LEH infusion at 10% of estimated blood volume (n = 10) did not affect mortality (30%, p < .05) and serum tumor necrosis factor-alpha levels (6204 +/- 414, p < .05) induced by 3.6 mg/kg Escherichia coli endotoxin administered (intravenous bolus) 22 h later. In contrast, when a shorter LEH-endotoxin time interval (<12 h, n = 10) or a higher dose of endotoxin (14.4 mg/kg, n = 20) was tested, LEH enhanced endotoxin-induced mortality (90% and 100%, respectively, p < .05) and broadened serum tumor necrosis factor-alpha response without modifying its peak levels. LEH (n = 20) did not exacerbate the endotoxin-induced tachycardia, leukopenia, and thrombocytopenia. Therefore, in this model, the effect of LEH on endotoxin-induced responses was dependent on the time interval between LEH and endotoxin administration as well as the endotoxin dose. The clinical relevance of these results should be further investigated.

摘要

脂质体包裹的血红蛋白(LEH)是一种实验性的携氧复苏液。由于LEH主要通过网状内皮系统从循环中清除,其对脓毒症发展的影响仍是一个主要关注点。因此,本研究旨在评估LEH是否会改变清醒、血容量正常大鼠内毒素血症的后果。以估计血容量的10%输注LEH(n = 10)对22小时后静脉推注3.6 mg/kg大肠杆菌内毒素所诱导的死亡率(30%,p < 0.05)和血清肿瘤坏死因子-α水平(6204 ± 414,p < 0.05)没有影响。相比之下,当测试较短的LEH - 内毒素时间间隔(<12小时,n = 10)或更高剂量的内毒素(14.4 mg/kg,n = 20)时,LEH提高了内毒素诱导的死亡率(分别为90%和100%,p < 0.05),并扩大了血清肿瘤坏死因子-α反应,但未改变其峰值水平。LEH(n = 20)并未加重内毒素诱导的心动过速、白细胞减少和血小板减少。因此,在该模型中,LEH对内毒素诱导反应的影响取决于LEH与内毒素给药之间的时间间隔以及内毒素剂量。这些结果的临床相关性应进一步研究。

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