Synthetic retinoids improve survival in rodent model of endotoxic shock

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 ann interventions- 31 male Sprague Dawley rats randomised into four groups: controls, given vehicle alone (n = 6), LPS 6 mg/kg body weight alo ne (n = 12), and LPS 6mg/kg but pretreated with the retinoic acid receptor- a (RAR-alpha() agonists CD336 (n = 6) and CD2081 (n = 7). Main outcome measures- Arterial blood pressure and heart rate measured hour ly 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 pres sure or heart rate. Conclusion- Pretreatment with selective synthetic RAR-alpha agonists improv es survival after LPS-induced septic shock in rats. These agents may have t herapeutic potential in the treatment of septic shuck in humens.