Department of Anesthesiology and Intensive Care, Lund University and Lund University Hospital, Sweden.
Microvasc Res. 2011 Nov;82(3):339-45. doi: 10.1016/j.mvr.2011.08.008. Epub 2011 Aug 28.
A key feature of sepsis is hypovolemia due to increased microvascular permeability. It has been suggested that the negative charge of albumin and of the endothelial glycocalyx is important for maintenance of the normally low permeability for albumin. Here we tested the hypothesis that charge effects contribute to the increased permeability in sepsis. Transcapillary escape rate (TER) and initial distribution volume for (125)I-labeled bovine serum albumin (BSA, isoelectric point pH 4.6) and for (131)I-labeled charge modified BSA (cBSA, average isoelectric point, pH 7.1) was measured 3h after sepsis was induced by cecal ligation and incision (CLI) (n=11) and in control animals (n=12). The importance of charge for permeability in sepsis was estimated by comparing the ratio between TER for cBSA and TER for BSA during control conditions to that after CLI. Plasma concentration of the glycocalyx component glycosaminoglycans (GAGs) was measured in separate control and CLI animals. The initial distribution volume for BSA and cBSA in control animals was 38 ± 3 ml/kg and 47 ± 4 mL/kg and decreased by 17% and 19%, respectively, following CLI. TER for BSA increased from 16.7 ± 4.1% in the controls to 20.1 ± 1.9% following CLI. Corresponding values for cBSA were 26.7 ± 5.6% and 29.8 ± 3.5%, respectively. The ratio between TER for cBSA and TER for BSA was 1.62 ± 0.1 in the control group and 1.49 ± 0.1 following CLI (p<0.05). Plasma GAG concentrations were higher in CLI animals than in the control group. We conclude that CLI induce hypovolemia secondary to increased microvascular permeability. Negative charge contributes to the normally low permeability of albumin and the importance of charge is decreased in early experimental sepsis. The observed charge effects are associated with CLI-induced breakdown of the glycocalyx.
脓毒症的一个主要特征是由于微血管通透性增加导致的血容量不足。有人提出，白蛋白和内皮糖萼的负电荷对于维持白蛋白通常的低通透性是很重要的。在这里，我们测试了这样一种假设，即电荷效应有助于增加脓毒症的通透性。在盲肠结扎和切开术（CLP）后 3 小时，测量了跨毛细血管逃逸率（TER）和（125）I 标记牛血清白蛋白（BSA，等电点 pH4.6）和（131）I 标记电荷修饰的 BSA（cBSA，平均等电点，pH7.1）的初始分布容积（n=11）和在对照动物中（n=12）。通过比较对照条件下 cBSA 的 TER 与 CLP 后 cBSA 的 TER 的比值，来估计电荷对脓毒症通透性的重要性。在单独的对照和 CLP 动物中测量了糖萼成分糖胺聚糖（GAGs）的血浆浓度。在对照动物中，BSA 和 cBSA 的初始分布容积分别为 38±3ml/kg 和 47±4ml/kg，CLP 后分别下降 17%和 19%。BSA 的 TER 从对照中的 16.7±4.1%增加到 CLP 后的 20.1±1.9%。相应的 cBSA 值分别为 26.7±5.6%和 29.8±3.5%。对照中 cBSA 与 BSA 的 TER 比值为 1.62±0.1，CLP 后为 1.49±0.1（p<0.05）。CLP 动物的血浆 GAG 浓度高于对照组。我们得出结论，CLP 导致血容量不足继发于微血管通透性增加。负电荷有助于白蛋白的正常低通透性，而在早期实验性脓毒症中，电荷的重要性降低。观察到的电荷效应与 CLP 诱导的糖萼破裂有关。
