Abstract 563: Fibroblast Infiltration Reduces Conduction Velocity and Leads to Reentry Multiplication in Cardiomyocyte Monolayers
Background: Cardiac fibrosis acts as an electrical obstacle and is thought to cause discontinuous propagation and arrhythmias. Fibrosis results from proliferation of fibroblasts which can form gap junctions with myocytes.
Methods and Results: We conducted optical mapping experiments in 35 x 35 mm hetero-cellular neonatal rat monolayers of cardiac origin to test the hypothesis that fibroblast infiltration modifies the dynamics of reentry. When one half of the monolayer had a randomly distributed myocyte/fibroblast mixture (~50/50%), and the other half had >95% myocytes, slow (2.75 Hz) sustained reentry stabilized in the region with more fibroblasts. The wavefronts propagated 2:1 to the 95% myocyte region at twice the conduction velocity (CV) (27.75 vs 12.86 cm/s). In separate experiments, as the percentage of fibroblasts in the monolayers was increased, the number of wavebreaks and reentry circuits increased and the excitation pattern became progressively more complex. In 4-s movies, when the preparations contained 5% fibroblasts, phase maps revealed only 1–2 singularity points corresponding to organizing cores of sustained reentrant activity. At 30% fibroblasts, the number of wavebreaks increased to 5±2 and the activity was much more irregular and disorganized. Finally, at 70% fibroblasts, the monolayers underwent extremely complex self-sustained activity with 42±5 repeated wavebreaks forming small wavelets that remained confined to small areas and rotated around their own singularity points. All wavelets rotated at the same frequency and the more stable ones clustered at or near the center of the preparations.
Conclusions: Co-culturing fibroblasts with myocytes significantly reduces CV while creating a substrate for increased stability and multiplication of reentry. These results predict that increased fibrosis in cardiac muscle would increase the complexity of wave propagation and reduce the frequency of reentry.