PO-455617-7 CHRONIC SYMPATHETIC REMODELING IN HEART FAILURE IMPACTS WHOLE-HEART CAMP SIGNALING AND ARRHYTHMOGENESIS.

Elevated sympathetic tone and b-AR desensitization are characteristics associated with heart failure (HF) contributors to the initiation of arrhythmia. Studies have shown that altered responsiveness in HF leads compartmentalization imparied sub-cellular cAMP signaling. Yet, if signaling is heterogeneously remodeled throughout intact heart, how this may contribute arrhythmia unknown. To assess whole-heart functional responses adrenergic activation HF. was induced via transverse aortic constriction cardiac specific CAMPER reporter mice, expressing a FRET-based biosensor. confirmed by echocardiography hearts were Langendorff-perfused for simultaneous Ca2+ imaging on an integrated optical mapping FRET system. Sham mice underwent same procedure but without aorta. Baseline levels, assessed as ratio, uniform ventricles male female hearts. Conversely, HF, baseline levels higher apex vs. base, particularly Low-dose b1-AR stimulation (100nM NE) led greater response Sham, across heart. In hearts, there trend toward basal, not apical regions. At high dose (500nM NE), had reduced compared mainly apex, where dose-dependent lost. Similar apex-base differences evident following b1 b2-AR (100-500nM Epi), lower Uniform accompanied shortening transient duration (CaTD) low stimulation. Following CaTD shorter than reduced. Moreover, no longer spatially uniform, shortened beyond basal regions stimulation, ventricular observed 8/10 vs 0/4 Using imaging, we activity became heterogeneous Heterogeneity heterogenous