Abstract 214: Sphingosine Kinase-1 Knockout Mice Have Increased Cardiac Arrest Mortality That is Rescued by Sphingosine-1-Phosphate Lyase Inhibition

Introduction: Sphingosine-1-phosphate (S1P) is an important regulator of pro-survival signaling. Two sphingosine kinases (SK), SK1 and SK2, form S1P in cells while S1P lyase irreversibly degrades S1P and controls the total pool of cellular sphingolipids. Deletion of the SK1 gene is detrimental in both in vitro and in vivo heart models of ischemia/reperfusion (I/R) injury. Using our mouse model of cardiac arrest and return of spontaneous circulation (CA/ROSC), we tested the hypothesis that SK1 knockout (SK1-KO) mice will demonstrate decreased survival after CA/ROSC, and that upregulation of S1P levels via pharmacologic S1P lyase inhibition will rescue the effect of SK1 gene deletion in this model. Methods: Control C57Bl/6 and SK1-KO mice were subjected to an established potassium-induced CA protocol. After 8 min CA, CPR was performed for 1.5 min, followed by an epinephrine bolus (1.5 μg/mouse) with continued CPR for an additional 3 min or until ROSC. Blood pressure, ETCO2, body temperature and ECG monitori...