TOTAL PARENTERAL-NUTRITION AND BOWEL REST MODIFY THE METABOLIC RESPONSE TO ENDOTOXIN IN HUMANS
TOTAL PARENTERAL-NUTRITION AND BOWEL REST MODIFY THE METABOLIC RESPONSE TO ENDOTOXIN IN HUMANS
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DOI：
10.1097/00000658-198910000-00005
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发表时间：
1989-10-01
影响因子：
9
通讯作者：
LOWRY, SF
中科院分区：
文献类型：
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作者：
FONG, YM;MARANO, MA;LOWRY, SF
肠粘膜萎缩，诱导全胃肠外营养（TPN）和/或肠休息时间延长，被假设为增强肠内毒素（LPS）易位，并可能改变宿主对感染的反应。为了研究TPN诱导的肠萎缩对LPS反应的影响，12名健康志愿者随机接受肠内喂养（ENT，n = 6）或7天的TPN不经口摄入（TPN，n = 6）。在研究阶段开始并在整个后续研究阶段持续进行恒定葡萄糖输注（50 mg/kg/h）时，在研究阶段前12小时终止肠内或TPN喂养。在放置动脉、肝静脉和股静脉导管后，在静脉内大肠杆菌LPS激发（20 U/kg）之前和之后6小时测定代谢参数。随后的动脉胰高血糖素峰值水平（ENT，189 . ±. 39 pg/mL; TPN，428 ±。48; p < 0.01）、动脉肾上腺素（ENT，236 . ±. 52 pg/mL，TPN，379 ±。49; p < 0.05）和肝静脉恶病质/肿瘤坏死因子（恶病质/TNF）（ENT，250 . ±. 56 pg/mL; TPN，479 ±。136; p < 0.05），TPN组显著高于ENT组。肢体乳酸流出（ENT，-16 . ±-. 4 μ g/ml-100cc组织，TPN，-52 ±。13; t = 2小时; p < 0.05）和氨基酸（ENT，-334 . 77 nmol/min-100 cc组织; TPN，-884 . ±. 58; t = 4小时; p < 0.05）在内毒素攻击后TPN受试者中更高。在TPN受试者中，毒素注射后24小时测量的循环C-反应蛋白（CRP）水平也显著更高（ENT，1.7 ± 0.01）。0.2 mg/dL; TPN，3.2 . ±. p < 0.1）。因此，TPN和肠道休息后，对LPS的反调节激素和内脏细胞因子反应增强。这与放大的急性期反应、外周氨基酸动员和外周乳酸产生有关。因此，先前的TPN可能通过过度的反调节激素反应以及增强的收缩期和内脏细胞因子产生来影响感染和脓毒症中观察到的代谢改变。
Intestinal mucosal atrophy, as induced by total parenteral nutrition (TPN) and/or prolonged bowel rest, is hypothesized to enhance bowel endotoxin (LPS) translocation and may alter host responses to infection. To examine the effect of TPN-induced bowel atrophy on the response to LPS, 12 healthy volunteers were randomized to receive either enteral feedings (ENT, n = 6) or seven days of TPN without oral intake (TPN, n = 6). Enteral or TPN feedings were terminated 12 hours before the study period when a constant dextrose infusion (50 mg/kg/hour) was initiated and continued throughout the subsequent study period. After placement of arterial, hepatic vein, and femoral vein catheters, metabolic parameters were determined before and for six hours after an intravenous Escherichia coli LPS challenge (20 U/kg). Subsequent peak levels of arterial glucagon (ENT, 189 .+-. 39 pg/mL; TPN, 428 .+-. 48; p < 0.01), arterial epinephrine (ENT, 236 .+-. 52 pg/mL, TPN, 379 .+-. 49; p < 0.05) and hepatic venous cachectin/tumor necrosis factor (cachectin/TNF) (ENT, 250 .+-. 56 pg/mL; TPN, 479 .+-. 136; p < 0.05) were significantly higher in the TPN group than in the ENT group. The extremity efflux of lactate (ENT, -16 .+-. 4 .mu.g/ml-100cc tissue, TPN, -52 .+-. 13; t = 2 hours; p < 0.05) and of amino acids (ENT, -334 .+-. 77 nmol/min-100cc tissue; TPN, -884 .+-. 58; t = 4 hours; p < 0.05) were higher in the TPN subjects after the endotoxin challenge. Circulating C-reactive Protein (CRP) levels measured 24 hours postendotoxin were also significantly higher in the TPN subjects (ENT, 1.7 .+-. 0.2 mg/dL; TPN, 3.2 .+-. p < 0.1). Hence the counter-regulatory hormone and splanchnic cytokine responses to LPS were enhanced after TPN and bowel rest. This is associated with a magnified acute-phase response, peripheral amino acid mobilization, and peripheral lactate production. Thus antecedent TPN may influence the metabolic alterations seen in infection and sepsis via both an exaggerated counter-regulatory hormone response as well as an enhanced systolic and splanchnic production of cytokines.