Effect of allopurinol on venous endothelial dysfunction after resuscitated hemorrhagic shock.
BACKGROUND
Blood flow deficits contribute to organ dysfunction in patients resuscitated from hemorrhage.


OBJECTIVE
To determine the contribution of xanthine oxidase mediated reperfusion injury to venous endothelial function after resuscitated hemorrhagic shock.


METHODS
Rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 60 min. Treatment animals received a 50mg/kg bolus and a 25mg/kg/h 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) and a non-hemorrhage group (No HS) served as control. Endothelial function was quantified at baseline, 30 min (R30) and 90 min (R90) post resuscitation as a change in mesenteric vessel diameter after topical application of acetylcholine (Ach), an endothelial dependent vasodilator.


RESULTS
Resuscitation restored cardiac output and blood pressure in both hemorrhage groups. First order venules (V1) demonstrated a 39% and a 36% reduction in ability to dilate to Ach at R30 and R90 after resuscitation with shed blood and Ringer's lactate (Std). Second order venules (V2) demonstrated a 20% and a 25% reduction in ability to dilate to Ach at R30 and R90 after resuscitation with shed blood and Ringer's lactate (Std). Addition of allopurinol to standard resuscitation attenuated this response resulting in the preservation of endothelial dependent venous vasodilation.


CONCLUSIONS
These data suggest that xanthine oxidase mediated ischemia-reperfusion injury contributes to venous endothelial dysfunction in the mesenteric microcirculation after resuscitated hemorrhagic shock. Endothelial function can be preserved by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation lending support for its inclusion as an adjunct to resuscitation after hemorrhagic shock.
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
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000503:physiopathology* / Q000628:therapy*; D013152:Splanchnic Circulation; D014680:Veins / Q000187:drug effects / Q000503:physiopathology*; D014969:Xanthine Oxidase / Q000502:physiology
D004791:Enzyme Inhibitors; D000493:Allopurinol; D014969:Xanthine Oxidase