CHANGE IN CONDUCTION VELOCITY DUE TO 2D FIBER CURVATURE IN CULTURED NEONATAL RAT VENTRICULAR MYOCYTES by ELLIOT BLAKE BOURGEOIS JACK M. ROGERS, COMMITTEE CHAIR

Continuum modeling of two-dimensional curved fiber fields has suggested that fiber curvature modulates conduction velocity (CV) in the myocardium. To verify the existence of this effect in living tissue, we measured CV in macroscopically anisotropic monolayers of cultured neonatal rat ventricular myocytes with controlled fiber curvature. A novel growth-directing substrate was used to produce fiber fields with significant curvature (78 ̊/cm to 333 ̊/cm). Anisotropy ratios (longitudinal CV / transverse CV) measured in cultures grown using this method (n=32) were 2.3±0.3, which is similar to the anisotropy exhibited by human ventricular myocardium. Propagating wavefronts were initiated transverse to fiber orientation in two alternating directions (with respect to fiber curvature) using unipolar stimulation. Action potentials were recorded using a voltage-sensitive fluorescent dye (di-4-ANEPPS) and a high speed digital video camera. A statistically significant (p=0.00033) change in CV was observed when propagation direction was reversed with respect to the direction of fiber curvature. The measured change in CV was 0.38±0.44 cm/s for all samples (n=24). A control group of cultures with uncurved transverse fiber orientation was also studied, and a 0.06±0.18 cm/s (p=NS) difference in CV was measured for propagation in both directions in this group (n=8). We conclude that fiber curvature can affect CV and may be involved in arrhythmiogenesis, for example, by promoting wavebreak or conduction block.