Spain D A, Kawabe T, Keelan P C, Wilson M A, Harris P D, Garrison R N
Departments of Surgery and Physiology and Biophysics, University of Louisville, Louisville, Kentucky, 40292, USA.
J Surg Res. 1999 Jun 15;84(2):180-5. doi: 10.1006/jsre.1999.5638.
The two-hit theory of multiple organ dysfunction syndrome proposes that an initial insult primes the host for an altered response to subsequent stimuli. We have previously documented enhanced dilator tone in the small intestine after a two-hit insult; however, the effects on vasoconstrictor function are unknown. We postulated that prior hemorrhage and resuscitation followed by bacteremia would alter microvascular responsiveness to alpha-adrenergic stimulation.
Male Sprague-Dawley rats underwent fixed-volume hemorrhage with resuscitation (H/R) or sham procedure (Sham). At 24 or 72 h, in vivo videomicroscopy of the small intestine was performed (inflow A1 and premucosal A3 arterioles). Constrictor function was assessed by topical application of norepinephrine (NE; 10(-8)-10(-6) M) before and 1 h after intravenous Escherichia coli or saline.
Sham, 24 or 72 h H/R, and E. coli alone produced no significant changes in A1 or A3 response to NE. Sequential H/R + E. coli resulted in decreased constrictor response in both A1 (72 h H/R + E. coli-38% from baseline vs Sham - 54%, P < 0.05) and A3 arterioles (-8% vs -51%, P < 0.05) at high doses of NE (10(-6) M).
Prior H/R primes the intestinal microvasculature for an altered response during a subsequent stress and these effects persist for up to 72 h following H/R. Sequential insults in this two-hit model caused marked hyporesponsiveness to NE. These alterations in control of microvascular tone might contribute to the hemodynamic compromise of sepsis, impair mucosal blood flow, and contribute to the development of MODS.
多器官功能障碍综合征的双打击理论认为，初始损伤会使宿主对后续刺激的反应发生改变。我们之前已记录到双打击损伤后小肠扩张肌紧张增强；然而，其对血管收缩功能的影响尚不清楚。我们推测，先前的出血和复苏后再发生菌血症会改变微血管对α-肾上腺素能刺激的反应性。
雄性Sprague-Dawley大鼠接受固定容量出血并复苏（H/R）或假手术（假手术组）。在24或72小时时，对小肠进行体内视频显微镜检查（流入动脉A1和黏膜前动脉A3）。在静脉注射大肠杆菌或生理盐水前及1小时后，通过局部应用去甲肾上腺素（NE；10(-8)-10(-6)M）评估收缩功能。
假手术组、24或72小时H/R组以及单独大肠杆菌处理组对NE的A1或A3反应均无显著变化。序贯H/R + 大肠杆菌导致高剂量NE（10(-6)M）时A1（72小时H/R + 大肠杆菌组 - 较基线下降38%，假手术组 - 下降54%，P < 0.05）和A3小动脉（-8% vs -51%，P < 0.05）的收缩反应降低。
先前的H/R使肠道微血管在后续应激期间反应改变，且这些效应在H/R后可持续长达72小时。此双打击模型中的序贯损伤导致对NE的显著低反应性。微血管张力控制的这些改变可能导致脓毒症的血流动力学损害、损害黏膜血流，并促成多器官功能障碍综合征的发生。
