Garrison R N, Spain D A, Wilson M A, Keelen P A, Harris P D
Department of Surgery, University of Louisville, Louisville Veterans Administration Medical Center, Kentucky 40292, USA.
Ann Surg. 1998 Jun;227(6):851-60. doi: 10.1097/00000658-199806000-00008.
The objective was to determine intestinal microvascular endothelial cell control after sequential hemorrhage and bacteremia.
Sepsis that follows severe hemorrhagic shock often results in multiple system organ failure (MSOF) and death. The sequential nature of this clinical scenario has led to the idea of a "two-hit" theory for the development of MSOF, the hallmark of which is peripheral vasodilation and acidosis. Acute bacteremia alone results in persistent intestinal vasoconstriction and mucosal hypoperfusion. Little experimental data exist to support the pathogenesis of vascular dysregulation during sequential physiologic insults. We postulate that hemorrhagic shock followed by bacteremia results in altered microvascular endothelial cell control of dilation and blood flow.
Rats underwent volume hemorrhage and resuscitation. A sham group underwent the vascular cannulation without hemorrhage and resuscitation, and controls had no surgical manipulation. After 24 and 72 hours, the small intestine microcirculation was visualized by in vivo videomicroscopy. Mean arterial pressure, heart rate, arteriolar diameters, and A1 flow by Doppler velocimetry were measured. Endothelial-dependent dilator function was determined by the topical application of acetylcholine (ACh). After 1 hour of Escherichia coil bacteremia, ACh dose responses were again measured. Topical nitroprusside was then applied to assess direct smooth muscle dilation (endothelial-independent dilator function) in all groups. Vascular reactivity to ACh was compared among the groups.
Acute bacteremia, with or without prior hemorrhage, caused significant large-caliber A1 arteriolar constriction with a concomitant decrease in blood flow. This constriction was blunted at 24 hours after hemorrhage but was restored to control values by 72 hours. There was a reversal of the response to bacteremia in the premucosal A3 vessels, with a marked dilation both at 24 and 72 hours. The sequence of hemorrhage and E. coli resulted in a progressive enhanced reactivity to the endothelial-dependent stimulus of ACh in the A3 vessels at 24 and 72 hours. Reactivity to endothelial-independent smooth muscle relaxation and subsequent vessel dilation was similar for all groups.
These data indicate that there is altered endothelial control of the intestinal microvasculature after hemorrhage in favor of enhanced dilator mechanisms in premucosal vessels with enhanced constrictor forces in inflow vessels. This enhanced dilator sensitivity is most evident in small premucosal vessels. This experimental finding supports the premise that an initial pathophysiologic stress alters the subsequent microvascular blood flow responses to systemic inflammation. These changes in the intestinal microcirculation are in concert with the "two-hit" theory for MSOF.
确定在相继发生出血和菌血症后肠道微血管内皮细胞的调控情况。
严重失血性休克后继发的脓毒症常导致多系统器官衰竭（MSOF）和死亡。这种临床情况的相继发生引发了MSOF发病机制的“两次打击”理论，其标志是外周血管扩张和酸中毒。单纯急性菌血症会导致持续性肠道血管收缩和黏膜灌注不足。几乎没有实验数据支持相继发生生理损伤期间血管调节异常的发病机制。我们推测，出血性休克后继发菌血症会导致微血管内皮细胞对扩张和血流的调控发生改变。
对大鼠进行容量性出血和复苏。假手术组进行血管插管但不进行出血和复苏，对照组不进行手术操作。在24小时和72小时后，通过体内视频显微镜观察小肠微循环。测量平均动脉压、心率、小动脉直径以及用多普勒测速仪测量的A1血流。通过局部应用乙酰胆碱（ACh）来测定内皮依赖性舒张功能。在大肠杆菌菌血症1小时后，再次测量ACh剂量反应。然后在所有组中局部应用硝普钠以评估直接平滑肌舒张（非内皮依赖性舒张功能）。比较各组对ACh的血管反应性。
急性菌血症，无论有无先前的出血，都会导致大口径A1小动脉显著收缩，同时血流减少。这种收缩在出血后24小时减弱，但在72小时恢复到对照值。黏膜前A3血管对菌血症的反应发生逆转，在24小时和72小时均有明显扩张。出血和大肠杆菌感染的顺序导致在24小时和72小时时A3血管对ACh的内皮依赖性刺激的反应性逐渐增强。所有组对非内皮依赖性平滑肌舒张和随后血管扩张的反应性相似。
这些数据表明，出血后肠道微血管内皮调控发生改变，有利于黏膜前血管中舒张机制增强，而流入血管中收缩力增强。这种增强的舒张敏感性在小黏膜前血管中最为明显。这一实验发现支持了最初的病理生理应激会改变随后微血管对全身炎症的血流反应这一前提。肠道微循环的这些变化与MSOF的“两次打击”理论相一致。
