XANTHINE-OXIDASE INHIBITION PREVENTS MESENTERIC BLOOD-FLOW DEFICITS AFTER RESUSCITATED HEMORRHAGIC-SHOCK BY PRESERVING ENDOTHELIAL FUNCTION

To determine the contribution of xanthine oxidase-mediated endothelial dysfunction to the blood flow deficits seen in the mesenteric circula tion after resuscitated hemorrhagic shock, rats were prepared for intr avital microscopic study then bled to 50% of baseline blood pressure f or 60 min. Treatment animals received a 50 mg/kg bolus and a 25 mg/kg/ hr infusion of the xanthine oxidase inhibitor allopurinol (allo) after shock but before resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group (Std Res) and a nonh emorrhage group served as controls. Endothelial function was quantifie d at baseline, 30 min (R30), and 90 min (R90) postresuscitation as a c hange in mesenteric vessel diameter after topical application of acety lcholine (Ach), an endothelial-dependent vasodilator. Resuscitation re stored cardiac output and blood pressure in both groups. First-order a rteriolar blood how (A1) remained depressed in the Std Res group but w as restored to baseline in the group treated with allo. A1 arterioles demonstrated a 22 and a 27% reduction in ability to dilate to Ach at R 30 and R90 after Std Res. V1 venules demonstrated a 39 and a 36% reduc tion in ability to dilate to Ach at R30 and R90 after Std Res. Endothe lial-dependent vasodilation and blood flow were preserved in the group receiving Std Res plus allo. The preservation of endothelial function correlated with the restoration of microvascular blood how postresusc itation. These data suggest that xanthine oxidase-mediated ischemia-re perfusion injury contributes to endothelial dysfunction and blood flow deficits in the mesenteric microcirculation after resuscitated hemorr hagic shock, the effect of which can be attenuated by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation. (C) 1997 Academic Press.