Abstract 1344: Biphasic Effect of Electrotonic Fibroblast-Myocyte Coupling on 2D Wave Conduction Velocity and Reentry
Fibroblast proliferation is common to various cardiac diseases. Differentiation of fibroblasts into myofibroblasts may result in myocyte-fibroblast electrical coupling via gap junctions. We hypothesized that fibroblast proliferation and varying heterocellular coupling significantly alter 2-dimensional cardiac wave propagation and reentry dynamics.
Methods: Monolayers of co-cultured fibroblasts and myocytes from neonatal rat ventricles were optically mapped. The junctional coupling was reduced using Cx43 RNA silencer in the fibroblasts. Simulations were used to quantify the effects of heterocellular coupling variation. Conduction velocity (CV) was measured when pacing at 2 Hz.
Results: Experiments and simulations show linear CV and reentry frequency reduction with increased number of wavebreaks as fibroblast/myocyte mixed area ratio increases. However, simulations show that the effect of fibroblast-myocyte coupling on CV and reentry frequency is biphasic: as coupling increases reentry frequency and CV initially decrease and then increase. Panel A shows that for a 1/4 fibroblasts/myocytes mixture the minimum CV is at ~10% of the myocytes coupling. In both experiments and simulations, low heterocellular coupling can result in similar CV and frequency of rotation (p<0.05), but more fragmented wavefronts as compared with high coupling (panel B).
Conclusion: Fibroblasts may have a dual role as current “sinks” and “transmitters”, depending on the level of heterocellular coupling. This study provides novel insight into the mechanisms whereby electrical interactions between myocytes and fibroblasts modify wave propagation and the propensity to arrhythmias.