Administration of polymerized bovine hemoglobin improves survival in a rat model of traumatic shock.
The ability of purified and modified hemoglobin solutions to expand blood volume and act as oxygen and carbon dioxide transporters with no apparent toxic side effects has lead to an increased interest in their utilization in shock conditions. Although hemoglobin solutions have been shown to provide beneficial effects in endotoxic and hemorrhagic shock, they have not been studied in whole body traumatic injury. We investigated the effects of a polymerized bovine hemoglobin solution (HBOC-201) in a rat model of traumatic shock. Pentobarbital-anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by marked hypotension, a survival time of 102 +/- 20 min, significant increases in intestinal myeloperoxidase (MPO) activity and splanchnic vascular endothelial dysfunction characterized by an impaired vasorelaxation of the superior mesenteric artery (SMA) to endothelium-dependent vasodilators. Traumatized rats were treated with HBOC-201 or an equal volume of vehicle corresponding to 5, 10 or 15% of the calculated blood volume. Treatment with HBOC-201 10 min posttrauma prolonged survival, normalized mean arterial blood pressure and attenuated endothelial dysfunction of the SMA. However, administration of HBOC-201 failed to significantly attenuate increases in intestinal MPO activity following trauma. No beneficial effects were observed with the administration the vehicle. These data indicate that HBOC-201 exerts significant beneficial effects in traumatic shock states by normalizing systemic blood pressure and attenuating vascular endothelial dysfunction. HBOC-201 may serve as a useful adjunctive agent in the early treatment of trauma.
Hayward
R
R
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Lefer
A M
AM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000494:pharmacology*; D002417:Cattle; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects / Q000201:enzymology; D066298:In Vitro Techniques; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012774:Shock, Traumatic / Q000188:drug therapy* / Q000401:mortality*; D016019:Survival Analysis
D001802:Blood Substitutes; D006454:Hemoglobins; C096798:HBOC 201; D009195:Peroxidase