Conhaim R L, Watson K E, Potenza B M, Harms B A
Department of Surgery, University of Wisconsin-Madison Medical School Madison, USA.
J Trauma. 1999 May;46(5):800-8; discussion 808-10. doi: 10.1097/00005373-199905000-00007.
Gram-negative lipopolysaccharide (LPS) has been demonstrated to increase pulmonary capillary permeability as judged by the increased flow of protein-rich lymph from the lungs of sheep infused with LPS. This finding suggests that LPS-injured pulmonary capillaries might be less restrictive than uninjured capillaries to the filtration of large hetastarch molecules. Hetastarch has a broad molecular mass spectrum (35-1,500 kilodaltons (kDa)), and one way to test the restrictiveness of pulmonary capillaries is to measure the size of the largest hetastarch molecules that cross the microvascular barrier and enter the lymph. To evaluate the effects of LPS, we compared hetastarch molecular distributions in the lung lymph of normal and LPS-injured sheep.
Adult sheep (38.2 +/- 0.8 kg) were surgically prepared for the collection of lung lymph, with study initiation after a 5- to 7-day recovery period. Hetastarch (6%) was infused (10 mL/kg) 24 hours before study to allow for stabilization of the hetastarch molecular distribution. On the day of study, LPS (Escherichia coli lipopolysaccharide, 2 microg/kg; n = 6) was infused, and plasma and lymph samples were collected for 12 hours. An additional group of animals not infused with LPS (n = 6) served as controls. Hetastarch molecular distributions in plasma and lymph were measured by using high performance size exclusion chromatography.
In control sheep, the largest hetastarch molecules in lymph averaged 861 +/- 18 kDa (mean +/- SEM) (plasma, 1,065 +/- 18 kDa). In LPS-treated sheep, the largest hetastarch molecules in lymph averaged 845 +/- 19 kDa (not significant vs. normal) (plasma, 1,025 +/- 14 kDa). Hetastarch concentrations in plasma and lung lymph of normal sheep, respectively, were 0.61 +/- 0.05% and 0.34 +/- 0.07%. In LPS-treated sheep, hetastarch concentrations in plasma and lymph were 0.56 +/- 0.08 (not significant vs. normal) and 0.29 +/- 0.07, respectively (p < or = 0.05). Lymph concentrations were lower after LPS because of increased lymph flows (19.9 +/- 5.4 mL/30 min, compared with 3.6 +/- 0.8 mL/30 min in normal sheep).
Our results suggest that LPS does not alter the diameter of the largest pores perforating the walls of pulmonary capillaries. Rather, the number of these pores in the capillary wall appears to be increased. This increase would explain why lymph flows rise after LPS with little change in the lymph protein concentration. Our results are also consistent with a filtration model in which capillaries are assumed to be perforated by small pores (protein reflection coefficient = 1) as well as large pores (protein reflection coefficient = 0).
革兰氏阴性菌脂多糖（LPS）已被证明可增加肺毛细血管通透性，这可通过向输注LPS的绵羊肺部注入富含蛋白质的淋巴液流量增加来判断。这一发现表明，LPS损伤的肺毛细血管对大分子羟乙基淀粉分子的滤过限制可能比未损伤的毛细血管小。羟乙基淀粉具有广泛的分子量范围（35 - 1500千道尔顿（kDa）），检测肺毛细血管限制程度的一种方法是测量穿过微血管屏障进入淋巴的最大羟乙基淀粉分子的大小。为评估LPS的影响，我们比较了正常和LPS损伤绵羊肺淋巴中羟乙基淀粉的分子分布。
成年绵羊（38.2±0.8千克）经手术准备用于收集肺淋巴，在5至7天的恢复期后开始研究。在研究前24小时输注6%的羟乙基淀粉（10毫升/千克），以使羟乙基淀粉分子分布稳定。在研究当天，输注LPS（大肠杆菌脂多糖，2微克/千克；n = 6），并在12小时内收集血浆和淋巴样本。另一组未输注LPS的动物（n = 6）作为对照。通过高效尺寸排阻色谱法测量血浆和淋巴中羟乙基淀粉的分子分布。
在对照绵羊中，淋巴中最大的羟乙基淀粉分子平均为861±18 kDa（平均值±标准误）（血浆中为1065±18 kDa）。在LPS处理的绵羊中，淋巴中最大的羟乙基淀粉分子平均为845±19 kDa（与正常相比无显著差异）（血浆中为1025±14 kDa）。正常绵羊血浆和肺淋巴中的羟乙基淀粉浓度分别为0.61±0.05%和0.34±0.07%。在LPS处理的绵羊中，血浆和淋巴中的羟乙基淀粉浓度分别为0.56±0.08（与正常相比无显著差异）和0.29±0.07（p≤0.05）。LPS处理后淋巴浓度较低是因为淋巴流量增加（19.9±5.4毫升/30分钟，而正常绵羊为3.6±0.8毫升/30分钟）。
我们的结果表明，LPS不会改变穿过肺毛细血管壁的最大孔的直径。相反，毛细血管壁上这些孔的数量似乎增加了。这种增加可以解释为什么LPS处理后淋巴流量增加而淋巴蛋白浓度变化不大。我们的结果也与一种滤过模型一致，该模型假设毛细血管由小孔（蛋白质反射系数 = 1）和大孔（蛋白质反射系数 = 0）穿孔。
