Uniaxial strain parallel to impulse propagation in cultured mouse and rat cardiomyocyte strands slows conduction more than strain in the perpendicular direction

Aim: Cardiac tissue deformation can modify tissue resistance, membrane capacitance and ion currents, and hence cause arrhythmogenic slow conduction. Our aim was to investigate whether uniaxial strain causes different changes in conduction velocity (θ) when applied parallel vs. perpendicular to impulse propagation. Methods: Cardiomyocyte strands were cultured on stretchable custom microelectrode arrays and θ was determined during steady-state pacing. Uniaxial strain (5%), either parallel to (orthodromic) or perpendicular to (paradromic) propagation, was applied for 1 min and controlled by imaging a grid of markers. The results were analysed in terms of cable theory. Results: Both types of strain induced immediate changes of θ upon application and release. In material coordinates, orthodromic strain decreased θ significantly more (p<0.001) than paradromic strain (2.2±0.5% vs 1.0±0.2% in n=8 mouse cardiomyocyte cultures, 2.3±0.4% vs 0.9±0.5% in n=4 rat cardiomyocyte cultures, respectively). The larger effect of orthodromic strain can be explained by the increase of axial myoplasmic resistance, which is not altered by paradromic strain. Thus, changes in tissue resistance substantially contributed to the changes of θ during strain, in addition to other influences (e.g., stretch-activated channels). Besides these immediate effects, the application of strain also consistently initiated a slow progressive decrease of θ and a slow recovery of θ upon release. Conclusion: Potentially arrhythmogenic changes in cardiac conduction caused by acute stretch do not only depend on the magnitude of strain itself but also on the orientation of strain relative to impulse propagation. This dependence is due to different effects on tissue resistance. MeSH keywords: Action Potentials; Biomechanical Phenomena; Electrophysiologic Techniques, Cardiac; Myocardium; Primary Cell Culture; Silicone Elastomers Buccarello et al. Cardiac conduction under uniaxial strain Page 3