Endocrine targets in experimental shock

Abstract

Modified resuscitation regimens and cytokine blockade/receptor antagonism after trauma have not been successful in decreasing the mortality rates from sepsis in trauma patients; therefore, an alternative approach using endocrine targets as modulators or inhibitors may be useful. Information regarding the influence of gender and hormones on immune and cardiovascular responses after nonthermal trauma-hemorrhagic shock is, on the one hand, considerable but, on the other hand, disappointingly incomplete. Trauma-hemorrhagic shock produces gender dimorphic immune and cardiovascular responses; men exhibit cardiovascular depression and are immunosuppressed, whereas proestrus women do not show cardiovascular or immunologic depression under those conditions. Furthermore, experimental studies have demonstrated the use of hormones, hormone antagonists, sex steroids, and receptor antagonists as salutary adjuncts, without any adverse effects on gastrointestinal, hepatic, and renal functions, for restoring the depressed immune and cardiovascular responses after trauma-hemorrhage. Thus, flutamide, dehydroepiandrosterone, metoclopramide, and 17beta-estradiol, which are readily availably clinically and do not produce any adverse hemodynamic effects, appear to be safe and novel agents/hormones for the treatment of immune and cardiovascular depression after severe blood loss in male and female trauma victims.