title: Modulation of diaspirin crosslinked hemoglobin induced systemic and regional hemodynamic response by ethanol in normal rats.
abstract: DCLHb, a hemoglobin based oxygen carrier, has been extensively studied for the treatment of hemorrhagic shock in both animal models and humans. Numerous accidents resulting in trauma are due to ethanol intoxication, in particular cases of car accidents. Therefore, trauma patients might be intoxicated with drugs of abuse like ethanol. Ethanol has significant effects on the cardiovascular system including peripheral vasodilation and decreased myocardial contractility. Such effects are likely to alter the cardiovascular actions of DCLHb, a resuscitative agent. Hence, this study investigated the effect of ethanol on the cardiovascular actions of DCLHb. Urethane anesthetized male Sprague-Dawley rats were divided into following groups (i) Saline + DCLHb (400 mg/kg) (n = 9), (ii) Ethanol (1 g/kg) + DCLHb (400 mg/kg) (n = 9), and (iii) Ethanol (4 g/kg) + DCLHb (400 mg/kg) (n = 8). Cardiovascular parameters were determined using a radioactive microsphere technique. DCLHb when administered to saline treated rats produced an increase in MAP, TPR, decreased renal and hepatic blood flow and increased blood flow to the skin and mesentery & pancreas. A high dose of ethanol (4 g/kg) significantly attenuated the DCLHb induced pressor response (p < 0.05) and increase in TPR (p < 0.05). Cardiac output was severely reduced by DCLHb in rats treated with high dose ethanol as compared to saline. No changes in TPR and cardiac output were observed in the low dose ethanol (1 g/kg) group. DCLHb reduced blood flow to the heart and mesentery & pancreas in rats treated with high dose ethanol. DCLHb caused a decrease in musculo-skeletal vascular resistance in rats treated with high dose ethanol. This decrease in vascular resistance in the musculo-skeletal system appears to be contributing to a decrease in TPR. It is concluded that ethanol in higher doses significantly alters the hemodynamic effects of DCLHb and may interfere with the resuscitative effects of DCLHb.
authors.affiliation: Department of Pharmaceutics and Pharmacodynamics, The University of Illinois at Chicago, 60612, USA.
authors.forename: R
authors.initials: R
authors.lastname: Palaparthy
authors.forename: B K
authors.initials: BK
authors.lastname: Saini
authors.forename: A
authors.initials: A
authors.lastname: Gulati
mesh_terms: D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology*; D001802:Blood Substitutes / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D006454:Hemoglobins / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects*; D013997:Time Factors
chemical_list: D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D006454:Hemoglobins; D000431:Ethanol; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin