Moeniralam H S, Bemelman W A, Romijn J A, Endert E, Ackermans M T, van Lanschot J J, Hermsen R C, Sauerwein H P
Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
J Surg Res. 1997 Nov;73(1):47-53. doi: 10.1006/jsre.1997.5190.
Different routes of endotoxin administration have been used to mimic inflammatory and metabolic responses observed during sepsis. Because the origin of endotoxemia may affect the reactions to endotoxin, we compared the induction of tumor necrosis factor (TNF), interleukin-6 (IL-6), hormones, and glucose production after endotoxin (1.0 microg/kg Escherichia coli 0111:B4) administration into a peripheral (n = 8) versus the portal (n = 8) vein in anesthetized dogs. Prior to endotoxin, a laparotomy was performed for cannulation of hepatic vessels. To evaluate the effects of surgery and anesthesia, we also studied the effects of peripheral endotoxin administration in six awake dogs. The rate of appearance of glucose was measured by primed continuous infusion of [6,6-2H2]glucose. In anesthetized dogs, arterial concentrations of TNF and IL-6 increased after endotoxin administration (P < 0.01 vs basal; NS between groups). Net hepatic TNF production was increased after endotoxin administration (peripheral vs portal endotoxin administration: 533 +/- 177 vs 2135 +/- 1127 ng/min, both P < 0.05 vs basal; NS between groups). Net hepatic IL-6 production was stimulated only after portal endotoxin delivery (from 86 +/- 129 to 4740 +/- 1899 ng/min, P < 0.05; NS between groups). Although there were no differences in neuroendocrine activation, portal endotoxin administration resulted in decreased glucose production compared with peripheral administration (13.6 +/- 0.9 vs 16.8 +/- 1.2 micromol/kg.min, P < 0. 05). In contrast to anesthetized dogs, endotoxin increased glucose production considerably in awake dogs from 13.8 +/- 1.2 to 24.2 +/- 3.2 micromol/kg.min (P < 0.05; P < 0.05 vs anesthetized dogs). The contribution of anesthesia and surgery increased the endotoxin-induced IL-6 response by approximately 350% compared with the effect of endotoxin in awake dogs (P < 0.01). In conclusion, there are no major differences in the responses to endotoxin between peripherally treated and portally treated dogs, except for differences in glucose production. Portal delivery compared with systemic delivery of endotoxin alters hepatic metabolism through nonendocrine mechanisms, reflected in decreased glucose production. The inflammatory, endocrine, and metabolic effects of endotoxin are altered by the combination of surgery and anesthesia.
已采用不同的内毒素给药途径来模拟脓毒症期间观察到的炎症和代谢反应。由于内毒素血症的起源可能影响对内毒素的反应，我们比较了在麻醉犬中经外周静脉（n = 8）与门静脉（n = 8）给予内毒素（1.0微克/千克大肠杆菌0111:B4）后肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）、激素及葡萄糖生成的诱导情况。在内毒素给药前，进行剖腹术以插管肝血管。为评估手术和麻醉的影响，我们还研究了六只清醒犬外周给予内毒素的效果。通过[6,6-2H2]葡萄糖的预充连续输注来测量葡萄糖的出现率。在麻醉犬中，给予内毒素后动脉血中TNF和IL-6浓度升高（与基础值相比P < 0.01；两组间无显著差异）。给予内毒素后肝脏净TNF生成增加（外周给予与门静脉给予内毒素：533±177对2135±1127纳克/分钟，两者与基础值相比P < 0.05；两组间无显著差异）。仅在门静脉给予内毒素后肝脏净IL-6生成受到刺激（从86±129至4740±1899纳克/分钟，P < 0.05；两组间无显著差异）。尽管神经内分泌激活无差异，但与外周给予相比，门静脉给予内毒素导致葡萄糖生成减少（13.6±0.9对16.8±1.2微摩尔/千克·分钟，P < 0.05）。与麻醉犬相反，内毒素使清醒犬的葡萄糖生成显著增加，从13.8±1.2至24.2±3.2微摩尔/千克·分钟（P < 0.05；与麻醉犬相比P < 0.05）。与清醒犬中内毒素的作用相比，麻醉和手术的影响使内毒素诱导的IL-6反应增加约350%（P < 0.01）。总之，除了葡萄糖生成的差异外，外周治疗犬与门静脉治疗犬对内毒素的反应无主要差异。与全身给予内毒素相比，门静脉给予内毒素通过非内分泌机制改变肝脏代谢，表现为葡萄糖生成减少。手术和麻醉的联合作用改变了内毒素的炎症、内分泌和代谢作用。
