Abstract 20353: Serum and Glucocorticoid-Regulated Kinase 1 (SGK1) Activation Predisposes to Lethal Reperfusion Ventricular Arrhythmias while Inhibition Is Protective in a Mouse Model of Ischemia-Reperfusion

Background: Transgenic (TG) mice with cardiac-specific expression of constitutively-active SGK1 (SGK1-CA) have cardiac dysfunction, ventricular arrhythmias (VA), and increased persistent Na current INaL. Expression of dominant negative SGK1 (SGK1-DN) in the heart protects against progression to heart failure following pressure-overload. We tested the hypothesis that SGK1 activation may be deleterious, while inhibition may be beneficial in a mouse model of ischemia/reperfusion (I/R). Methods: TG mice and age-matched wild-type (WT) littermates were subjected to 30 min. ischemia and either 24 hour (acute I/R) or 4 weeks reperfusion (chronic I/R). Heart rhythm was monitored acutely and by implanted recorders for 24 hours following I/R. Harvested hearts were analyzed for infarct size, area at risk and TUNEL positive cells. Results: SGK1-CA TG mice subjected to I/R had an increase in mortality (8/10) compared with WT (7/29) or SGK1-DN mice (2/16), p =0.006. There was a trend towards increased PVCs in the SGK-CA...