Abstract P2097: Hypochloremia Alters Cardiac Physiology After Myocardial Ischemia-Reperfusion Injury

Abstract

Ischemic heart disease (IHD) is one of the leading causes of death related due to heart failure (HF). It is mainly characterized by impairment of heart contraction-relaxation (rhythmicity) and cardiac output. While a myriad of cellular processes is associated with IHD, one of the major cellular aspects strongly associated is the electrolyte and ionic imbalance. Serum sodium levels have been a well-established adverse prognostic marker for patients with chronic heart failure. Recent evidences have suggested that the lower serum chloride (hypochloremia, &lt90mM) is associated with increased mortality risk in patients with chronic HF independent of serum sodium levels. Serum chloride (Cl - ) is a major anion in physiology but its correlation to IHD has not been studied extensively. Hence, to better understand the role of hypochloremia in HF patients, we reviewed patients who received a left ventricular assist device (LVAD) placement at The Ohio State University Medical Center. Survival analysis demonstrated that patients with hypochloremia before LVAD placement had decreased survival at one year compared to patients with normal serum Cl - (p=0.0055). Moreover, our e x vivo studies with isolated rat hearts indicate hypochloremia aggravates myocardial infarction post ischemia-reperfusion (IR) injury. Hence, to elucidate Cl - mediated signaling mechanism we incorporated highly translational human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Our cellular studies demonstrate that physiological alteration of extracellular Cl - affects the function of beating hiPSC-CM. Hypochloremia significantly increases the beating rate by reducing the calcium cycling durations in hiPSC-CM. Studies are ongoing to determine the involvement of the chloride channel in maintaining chloride homeostasis. Taken together, our results for the first time establish the novel role and mechanism of chloride homeostasis in IR injury. These results will advance the need to search for effective therapeutic approaches to target novel Cl - channels in IHD.