Project Summary Despite over a century of research into sudden cardiac arrest (SCA), survival from such an event remains abysmally low. Presently, treatment immediately following SCA consists of cardiopulmonary resuscitation (CPR) and intravenous fluid therapy. The proposed research seeks to challenge the paradigm that 0.9% normal saline (NS) is an ideal IV-fluid post-SCA. Undeterred by the nomenclature “normal saline,” neither the sodium concentration ([Na+]; 155mM) nor the chloride concentration (155mM) in NS falls within the normal physiological range for humans (Na+=135-147mM; Cl-=98-106mM). Previous research investigating the effects of manipulating extracellular sodium concentrations have demonstrated that increased sodium leads to impaired mechanical and metabolic function in heart. These studies however, were conducted in isolated cells with sodium concentrations far beyond clinical relevance. I will use an isolated, whole heart model to study the effect of hypernatremic perfusion (155mM Na+) on cardiac mechanical and metabolic function. To assess mechanical and metabolic function, I am going to use cardiac optical mapping, a technique in which fluorescent probes are loaded into the intact whole-heart and then imaged with high spatio-temporal resolution using a CMOS (complementary metal-oxide semiconductor) camera system, and transmission electron microscopy. The proposed study aims to lay the foundation for creating novel IV-fluids optimized to improve overall cardiac function and survival following cardiac arrest.