R. Hayward et Am. Lefer, Administration of polymerized bovine hemoglobin improves survival in a ratmodel of traumatic shock, METH FIND E, 21(6), 1999, pp. 427-433
Citations number
38
Categorie Soggetti
Pharmacology & Toxicology
Journal title
METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY
The ability of purified and modified hemoglobin solutions to expand blood v
olume and act as oxygen and carbon dioxide transporters with no apparent to
xic 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 s
tudied in whole body traumatic injury. We investigated the effects of a pol
ymerized bovine hemoglobin solution (HBOC-201) in a rat model of traumatic
shock. Pentobarbital-anesthetized rats subjected to Noble-Collip drum traum
a developed a shock state characterized by marked hypotension, a survival t
ime of 102 +/- 20 min, significant increases in intestinal myeloperoxide (M
PO) activity and splanchnic vascular endothelial dysfunction characterized
by an impaired vasorelaxation of the superior mesenteric artery (SMA) to en
dothelium-dependent vasodilators. Traumatized rats were treated with HBOC-2
01 or an equal volume of vehicle corresponding to 5, 10 or 15% of the calcu
lated blood volume. Treatment with HBOC-201 10 min posttrauma prolonged sur
vival, normalized mean arterial blood pressure and attenuated endothelial d
ysfunction of the SMA. However, administration of HBOC-201 failed to signif
icantly attenuate increases in intestinal MPO activity following trauma. No
beneficial effects were observed with the administration the vehicle. Thes
e data indicate the HBOC-201 exerts significant beneficial effects in traum
atic shock states by normalizing system blood pressure and attenuating vasc
ular endothelial dysfunction. HBOC-201 may serve as a useful adjunctive age
nt in the early treatment of trauma. (C)1999 Prous Science. All rights rese
rved.