Whiteford M, Spirig A, Rudolph A, Neville L, Abdullah F, Feuerstein G, Rabinovici R
Department of Surgery, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
Shock. 1998 Jun;9(6):428-33. doi: 10.1097/00024382-199806000-00007.
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.
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。