Synthetic retinoids improve survival in rodent model of endotoxic shock.

ABSTRACT

OBJECTIVE: To investigate the effect of synthetic retinoids on septic shock induced by lipopolysaccharide (LPS) in rats. DESIGN: Randomised study. SETTINGS University hospital laboratory, Sweden. ANIMALS AND INTERVENTIONS: 31 male Sprague Dawley rats randomised into four groups controls, given vehicle alone (n = 6), LPS 6 mg/kg body weight alone (n = 12), and LPS 6 mg/kg but pretreated with the retinoic acid receptor-alpha (RAR-alpha) agonists CD336 (n = 6) and CD2081 (n = 7). MAIN OUTCOME MEASURES: Arterial blood pressure and heart rate measured hourly for four hours; mortality. RESULTS: LPS caused a pronounced fall in blood pressure within one hour of injection in all groups of rats. Of the 12 rats given LPS but not RAR-alpha agonists, 6 died before the end of the experiment. By contrast, all animal given either CD336 or CD2081 survived. The significantly improved survival was found despite no significant improvements in either mean arterial pressure or heart rate. CONCLUSION: Pretreatment with selective synthetic RAR-alpha agonists improves survival after LPS-induced septic shock in rats. These agents may have therapeutic potential in the treatment of septic shock in humans.