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 circulation after resuscitated hemorrhagic shock, rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 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 nonhemorrhage group served as controls. Endothelial function was quantified at baseline, 30 min (R30), and 90 min (R90) postresuscitation as a change in mesenteric vessel diameter after topical application of acetylcholine (Ach), an endothelial-dependent vasodilator. Resuscitation restored cardiac output and blood pressure in both groups. First-order arteriolar blood flow (A1) remained depressed in the Std Res group but was 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 R30 and R90 after Std Res. V1 venules demonstrated a 39 and a 36% reduction in ability to dilate to Ach at R30 and R90 after Std Res. Endothelial-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 flow postresuscitation. These data suggest that xanthine oxidase-mediated ischemia-reperfusion injury contributes to endothelial dysfunction and blood flow deficits in the mesenteric microcirculation after resuscitated hemorrhagic shock, the effect of which can be attenuated by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation.
Flynn
W J
WJ
Department of Surgery, Erie County Medical Center, State University of New York at Buffalo 14215, USA.
Pilati
D
D
Hoover
E L
EL
D000109:Acetylcholine / Q000494:pharmacology; D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002302:Cardiac Output; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000503:physiopathology* / Q000628:therapy*; D013152:Splanchnic Circulation; D014664:Vasodilation; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000502:physiology
D004791:Enzyme Inhibitors; D000493:Allopurinol; D014969:Xanthine Oxidase; D000109:Acetylcholine