Increased intestinal permeability in endotoxic pigs. Mesenteric hypoperfusion as an etiologic factor.
Increased intestinal permeability in endotoxic pigs. Mesenteric hypoperfusion as an etiologic factor.
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DOI：
10.1001/archsurg.1991.01410260101014
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发表时间：
1991-02
影响因子：
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通讯作者：
Mitchell P. Fink;Jan B. Antonsson;Hailong Wang;H. R. Rothschild
中科院分区：
文献类型：
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作者：
Mitchell P. Fink;Jan B. Antonsson;Hailong Wang;H. R. Rothschild
给猪输注脂多糖（LPS）可降低上级肠系膜动脉血流量（Qsma），提示肠系膜灌注不足可能是LPS诱导的肠粘膜通透性改变的原因。为了验证这一假设，我们研究了四组麻醉的猪。第1组动物（N = 6）用LPS输注（从60分钟开始，在1小时内250微克/kg），并用林格氏乳酸盐（48 mL/kg/小时）连续复苏。在第2组（N = 5）中，通过机械封堵器将Qsma降低50%，以模拟在第I组中观察到的LPS诱导的Qsma变化。包括第3组（N = 5），以记录我们检测缺血/再灌注诱导的粘膜渗透性变化的能力;在这些猪中，Qsma逐步降低至零流量（在150至210分钟），然后恢复灌注（在210至270分钟）。第4组中的猪（N = 6）作为正常对照;这些动物以与第1组相同的速率用林格氏乳酸盐复苏，但不输注LPS。为了评估粘膜渗透性，我们测量了两种标记物（铬51标记的乙二胺四乙酸一水合物（EDTA）和尿素）的血浆-管腔清除率。静脉内给予标记物的负荷和维持输注，并在37 ℃下用乳酸林格氏液以2 mL/min连续灌注20 cm的分离小肠段。结果表示为两种探针的清除率比值（CEDTA/CUREA）。在第3组中，CEDTA/CUREA在270分钟时为基线的999% +/- 355%。在第1组中，270分钟时CEDTA/CUREA为基线的572% +/- 235%。然而，在第2组和第4组中，CEDTA/CUREA在研究期间与基线值相比没有显著变化。这些数据表明，增加粘膜通透性后LPS是由于因素以外（或除了）肠系膜灌注不足。
Infusing pigs with lipopolysaccharide (LPS) decreases superior mesenteric artery blood flow (Qsma), suggesting that mesenteric hypoperfusion may be responsible for LPS-induced alterations in gut mucosal permeability. To test this hypothesis, we studied four groups of anesthetized swine. Group 1 animals (N = 6) were infused with LPS (250 micrograms/kg over 1 hour beginning at 60 minutes) and continuously resuscitated with Ringer's lactate (48 mL/kg per hour). In group 2 (N = 5), Qsma was decreased by 50% by means of a mechanical occluder to mimic the LPS-induced alterations in Qsma observed in group I. Group 3 (N = 5) was included to document our ability to detect ischemia/reperfusion-induced alterations in mucosal permeability; in these pigs, Qsma was decreased in steps to zero flow (at 150 to 210 minutes) and then perfusion was restored (at 210 to 270 minutes). Pigs in group 4 (N = 6) served as normal controls; these animals were resuscitated with Ringer's lactate at the same rate as in group 1 but were not infused with LPS. To assess mucosal permeability, we measured plasma-to-lumen clearances for two markers, chromium 51-labeled edetic acid monohydrate (EDTA) and urea. Loading and maintenance infusions of the markers were given intravenously, and a 20-cm isolated segment of small intestine was continuously perfused at 2 mL/min with Ringer's lactate at 37 degrees C. Results were expressed as the ratio of the clearances for the two probes (CEDTA/CUREA). In group 3, CEDTA/CUREA was 999% +/- 355% of baseline at 270 minutes. In group 1, CEDTA/CUREA was 572% +/- 235% of baseline at 270 minutes. In groups 2 and 4, however, CEDTA/CUREA did not change significantly from the baseline value over the duration of the study. These data suggest that increased mucosal permeability after LPS is due to factors other than (or in addition to) mesenteric hypoperfusion.