Abstract 13598: Cardiac Electrical Remodeling Triggered by Mechanical Stretch: New Evidence From the Zebrafish Model
Background: Altered mechanical loading leading to hypertrophy and decompensated heart failure is a powerful risk factor for fatal arrhythmias. However, the mechanisms linking mechanical to electrical dysfunction in the heart are poorly understood. We have established for the first time a zebrafish model of stretch-induced ventricular electrical remodeling (VER) that combines high-precision localized stretch of an intact vertebrate heart with high-throughput genetics and high-resolution electrophysiology.
Methods: Ventricles from isolated zebrafish embryo hearts were stretched during field-pacing via attached 10-um-diameter carbon fibers (Figure A). Mechanical load was set at high precision by means of computer-controlled micromanipulators. Following stretch, VER was determined using high-speed, high-resolution fluorescence imaging of action potentials and calcium transients.
Results: Only 90 minutes of ventricular stretch induced persistent and localized VER in the ventricles of zebrafish embryo hearts that was characterized by prolonged action potentials (Figure B: 374±35ms stretched vs. 212±19ms control, p<0.01), slowed conduction (5.4±1.9mm/s stretched vs. 12.3±1.9mm/s control, p<0.05) and enhanced calcium transients (0.126±0.011 stretched vs. 0.079±0.008 control, ratiometric units F405/F495, p<0.01). Ventricular stretch did not affect the atrium. Afterdepolarizations which are known to trigger arrhythmias, were observed in stretched, but not in unstretched control hearts (2 of 5 stretched vs. 0 of 5 control).
Conclusions: These results suggest that the heart responds to stretch via a mechano-electrical feedback mechanism. The model reproduced the key electrophysiological phenotypes of the mammalian heart. By combining these methods we have created a unique assay for studying the various responses of an intact heart to stretch and to dissect the molecular pathways that lead to VER and contribute to arrhythmias.
- © 2011 by American Heart Association, Inc.