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Androstenetriol Improves Survival in a Severe Trauma Hemorrhagic Shock Model
Author(s) -
Marcu Andreea Cristina,
Barbee Robert W.,
Carter Hans,
Ivatury Rao R.,
Ward Kevin R.,
Loria Roger M.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1384-c
Traumatic shock activates a complex host response leading to overwhelming inflammation and immunosuppression resulting in sepsis, organ failure, and death. Androstenetriol (AET), is a more potent metabolite of dehydroepiandrosterone, that markedly up regulates host immune response, prevents immune suppression and modulates inflammation, leading to improved survival after lethal infections by pathogens and lethal radiation. AET improves survival in a conscious rodent model of combined hemorrhage and soft tissue trauma. The model consisted of a pressure driven protocol (n=29), in which after catheterization and soft tissue trauma, animals were hemorrhaged down to a 35–40 mmHg mean arterial pressure for over 1 hour time period. Resuscitation was initiated and a single subcutaneous injection of AET (40 mg/kg) or vehicle, blindly randomized, was administered along with the opiate and crystalloid fluids, followed by packed red blood cells. After resuscitation, animals were observed for hemodynamics and blood gases for 24 and 48 hours. In this study, mortality in the untreated group (n=16) was 69% (11/16). In contrast, AET treated animals (n=13) had a mortality rate of 31% (4/13), showing its protective effects (Fisher's Exact Test p<0.05). The results indicate that a single subcutaneous injection of the immune modulator ‐ AET, is highly effective in improving survival in a severe trauma‐hemorrhage shock model.