title: Alcohol potentiates postburn remote organ damage through shifts in fluid compartments mediated by bradykinin.
abstract: Of the 450,000 burn patients each year, 50% have a positive blood alcohol content, and this predisposes them to worsened clinical outcomes. Despite high prevalence and established consequences, the mechanisms responsible for alcohol-mediated complications of postburn remote organ damage are currently unknown. To this end, mice received a single dose of alcohol (1.12 g/kg) or water by oral gavage and were subjected to a 15% total body surface area burn. Animals with a burn alone lost ∼5% of their body weight in 24 h, whereas intoxicated and burned mice lost only 1% body weight (P < 0.05) despite a 17% increase in hematocrit (P < 0.05) and a 57% increase in serum creatinine (P < 0.05) over burn injury alone. This retention of water weight despite increased dehydration suggests that intoxication at the time of a burn causes a shift in fluid compartments that may exacerbate end-organ ischemia and damage as evidenced by a 3-fold increase in intestinal bacterial translocation (P < 0.05), a 30% increase (P < 0.05) in liver weight-to-body weight ratio, and an increase in alveolar wall thickness over a burn alone. Furthermore, administration of the bradykinin antagonist HOE140 30 min after intoxication and burn restored fluid balance and alleviated end-organ damage. These findings suggest that alcohol potentiates postburn remote organ damage through shifts in fluid compartments mediated by bradykinin.
authors.affiliation: *Alcohol Research Program, †Stritch School of Medicine, ‡Department of Surgery, §Burn and Shock Trauma Research Institute, Loyola University Chicago, Maywood, Illinois.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Chen
authors.forename: Eileen B
authors.initials: EB
authors.lastname: O'Halloran
authors.forename: Jill A
authors.initials: JA
authors.lastname: Ippolito
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kovacs
mesh_terms: D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists / Q000494:pharmacology*; D002056:Burns / Q000097:blood / Q000150:complications / Q000188:drug therapy; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000494:pharmacology; D003404:Creatinine / Q000097:blood; D003681:Dehydration / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology; D006400:Hematocrit; D006801:Humans; D007511:Ischemia / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D008297:Male; D051379:Mice
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; D002492:Central Nervous System Depressants; D000431:Ethanol; C065679:icatibant; D003404:Creatinine; D001920:Bradykinin