Decreased alpha-adrenergic response in the intestinal microcirculation after "two-hit" hemorrhage resuscitation and bacteremia

Background. The two-hit theory of multiple organ dysfunction syndrome propo ses that an initial insult primes the host for an altered response to subse quent stimuli. We have previously documented enhanced dilator tone in the s mall intestine after a two-hit insult; however, the effects on vasoconstric tor function are unknown. We postulated that prior hemorrhage and resuscita tion followed by bacteremia would alter microvascular responsiveness to alp ha-adrenergic stimulation. Methods. Male Sprague-Dawley rats underwent fixed-volume hemorrhage with re suscitation (H/R) or sham procedure (Sham). At 24 or 72 h, in vivo videomic roscopy of the small intestine was performed (inflow Al and premucosal A3 a rterioles). Constrictor function was assessed by topical application of nor epinephrine (NE; 10(-8)-10(-6) M) before and 1 h after intravenous Escheric hia coli or saline. Results. Sham, 24 or 72 h H/R, and E. coli alone produced no significant ch anges in A1 or A3 response to NE. Sequential H/R + E. coli resulted in decr eased 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 d oses of ME (10(-6) M). Conclusions. Prior H/R primes the intestinal microvasculature for an altere d response during a subsequent stress and these effects persist for up to 7 2 h following H/R. Sequential insults in this two-hit model caused marked h yporesponsiveness to NE. These alterations in control of microvascular tone might contribute to the hemodynamic compromise of sepsis, impair mucosal b lood flow, and contribute to the development of MODS. (C) 1999 Academic Pre ss.