Xanthine oxidase inhibition after resuscitated hemorrhagic shock restores mesenteric blood flow without vasodilation.
To determine the contribution of xanthine oxidase-mediated reperfusion injury to the blood flow deficits seen in the intestinal microcirculation 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/h infusion of the xanthine oxidase inhibitor allopurinol after shock but before standard resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group served as control. Blood flow and vessel diameters were measured in the neurovascularly intact terminal ileum using intravital microscopy and doppler velocimetry. Resuscitation restored cardiac output and blood pressure in both groups. Blood flow in first order arterioles 120 min postresuscitation was 41% of baseline in the standard resuscitation group and 77% of baseline in the allopurinol-treated group. A1 arteriolar diameter was not significantly different between the two groups, being 73 and 82% of baseline, respectively. These data suggest that xanthine oxidase-mediated ischemia-reperfusion injury contributes to blood flow deficits in the small intestinal microcirculation after resuscitated hemorrhagic shock and that the improvement in blood flow seen with allopurinol is not due to vasodilation within the microvasculature.
Flynn
W J
WJ
State University of New York at Buffalo, Department of Surgery, Erie County Medical Center 14215, USA.
Pilati
D
D
Hoover
E L
EL
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D013152:Splanchnic Circulation / Q000187:drug effects; D013481:Superoxides / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000187:drug effects
D013481:Superoxides; D000493:Allopurinol; D014969:Xanthine Oxidase