MICROVASCULAR CHANGES EXPLAIN THE 2-HIT THEORY OF MULTIPLE ORGAN FAILURE

Objective The objective was to determine intestinal microvascular endo thelial cell control after sequential hemorrhage and bacteremia. Summa ry Background Data Sepsis that follows severe hemorrhagic shock often results in multiple system organ failure (MSOF) and death. The sequent ial nature of this clinical scenario has led to the idea of a ''two-hi t'' theory for the development of MSOF, the hallmark of which is perip heral vasodilation and acidosis. Acute bacteremia alone results in per sistent intestinal vasoconstriction and mucosal hypoperfusion. Little experimental data exist to support the pathogenesis of vascular dysreg ulation during sequential physiologic insults. We postulate that hemor rhagic shock followed by bacteremia results in altered microvascular e ndothelial cell control of dilation and blood flow. Methods Rats under went volume hemorrhage and resuscitation. A sham group underwent the v ascular cannulation without hemorrhage and resuscitation, and controls had no surgical manipulation. After 24 and 72 hours, the small intest ine microcirculation was visualized by in vivo videomicroscopy. Mean a rterial pressure, heart rate, arteriolar diameters, and A1 flow by Dop pler velocimetry were measured. Endothelial-dependent dilator function was determined by the topical application of acetylcholine (ACh). Alt er 1 hour of Escherichia coli bacteremia, ACh dose responses were agai n measured. Topical nitroprusside was then applied to assess direct sm ooth muscle dilation (endothelial-independent dilator function) in all groups. Vascular reactivity to ACh was compared among the groups. Res ults Acute bacteremia, with or without prior hemorrhage, caused signif icant large-caliber Al arteriolar constriction with a concomitant decr ease in blood flow. This constriction was blunted at 24 hours after he morrhage but was restored to control values by 72 hours. There was a r eversal of the response to bacteremia in the premucosal A3 vessels, wi th a marked dilation both at 24 and 72 hours. The sequence of hemorrha ge and E, coil resulted in a progressive enhanced reactivity to the en dothelial-dependent stimulus of ACh in the A3 vessels at 24 and 72 hou rs. Reactivity to endolhelial-independent smooth muscle relaxation and subsequent vessel dilation was similar for ail groups. Conclusions Th ese data indicate that there is altered endothelial control of the int estinal 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 s mall premucosal vessels. This experimental finding supports the premis e that an initial pathophysiologic stress alters the subsequent microv ascular blood flow responses to systemic inflammation. These changes i n the intestinal microcirculation are in concert with the ''two-hit'' theory for MSOF.