Reverse cardiac remodeling

Cardiac mechanical unloading is associated with an increased risk of ventricular arrhythmias. Underlying pathophysiological mechanisms are still poorly understood. Recent studies indicate that unloading causes a remodeling of Ca2+ homeostasis in ventricular cardiomyocytes leading to a reduced contribution of sarcoplasmic reticulum (SR) Ca2+ release to the systolic Ca2+ transient. Using pharmacological and genetic interventions in a rodent model of cardiac unloading, this project tests the hypothesis that reestablishing the dominance of SR Ca2+ release will stabilize cardiac repolarization and therefore reduce the occurrence of arrhythmias.