Abstract 1405: Antifibrillatory Action of Increased Excitability in Neonatal Rat Ventricular Monolayers Overexpressing hSCN5A
Previous studies have suggested that a reduction of excitability through INa decrease in the ventricles may increase the likelihood of reentry and ventricular fibrillation (VF). We have investigated the molecular correlates of the relationship between excitability and the initiation of functional reentry through the vortex-shedding mechanism, which is demonstrable by the interaction of the wavefront with an impermeable barrier. We hypothesize that increased excitability will serve to reduce the likelihood of vortex shedding, wavebreak, and the ultimate initiation of reentry. We constructed 6 – 8 day old control (uninfected), GFP expressing (Ad-GFP), and sodium channel (NaCh) overexpressing (Ad-hSCN5a, molecular correlate for Nav 1.5, alpha subunit of the human NaCh) neonatal rat ventricular myocyte monolayers. Impulse propagation was optically imaged (Di-8-ANEPPS) at high spatio-temporal resolution (80x80, 0.4375 mm per pixel, 200 fps) as the impulse circumnavigated around an unexcitable obstacle (lesion.) Voltage clamp recordings showed a 71 fold increase in source current in single NaCh overexpressing mycoytes, thus improving the excitability. In the monolayers, the increased INa is reflected by a significant increase in conduction velocity (CV) at all frequencies studied (Panel A). Moreover, compared to control and GFP expressing monolayers, NaCh overexpressing monolayers presented a significantly (p<0.05, Chi-square) decreased incidence of vortex shedding (Panel B), preventing the initiation of reentry. This is the first demonstration in a biological system that increasing excitability through INa increase may be antiarrhythmic.