Abstract 20797: Sphingosine-1-Phosphate Receptor Agonist Fingolimod After Prolonged Circulatory Arrest Improves Cardiac and Neurological Outcomes in a Rat Model of Extracorporeal Life Support.

Introduction: Fingolimod, a sphingosine-1-phosphate receptor agonist, is used for the treatment of multiple sclerosis and exerts anti-inflammatory and antiapoptotic properties. Hypothesis: We hypothesized that sphingosine-1-phosphate receptor activation with fingolimod during circulatory arrest inhibits apoptosis and inflammation leading to increased myocardial and cerebral functions after reperfusion with extracorporeal life support (ECLS). Methods and Results: Ventricular fibrillation (VF) was induced in male Wistar rats. After 10 min of untreated VF, veno-arterial ECLS was instituted for 60 minutes. At the beginning of ECLS animals randomly received fingolimod or saline (control). Restoration of spontaneus circulation and 24 hours survival were higher in rats that received fingolimod (p = 0.03). Fingolimod treatment activated the cardioprotective reperfusion injury salvage kinase and survivor activating factor enhancement pathways leading to decreased cardiomyocyte apoptosis and reduced myocardial oxid...