Key result
In a computational model, electrical remodeling of the L-type calcium current driven by mechanoelectric feedback resulted in more homogeneous fiber shortening and increased heterogeneity in action potential duration.
Why the study?
Does electrical remodeling triggered by changes in mechanical load reduce heterogeneity in cardiomechanics induced by ventricular pacing in a computational model?
Does electrical remodeling triggered by changes in mechanical load reduce heterogeneity in cardiomechanics induced by ventricular pacing in a computational model?
This computational model study suggests that electrical remodeling may serve as a mechanism to reduce cardiomechanical heterogeneity induced by ventricular pacing.
No immediate clinical implications for pacing; leaves open whether mechanoelectric feedback mitigates dyssynchrony in vivo.
Regional variation in ionic membrane currents causes differences in action potential duration (APD) and is proarrhythmic. After several weeks of ventricular pacing, AP morphology and duration are changed due to electrical remodeling of the transient outward potassium current (I (to)) and the L-type calcium current (I (Ca,L)). It is not clear what mechanism drives electrical remodeling. By modeling the cardiac muscle as a string of segments that are electrically and mechanically coupled, we investigate the hypothesis that electrical remodeling is triggered by changes in mechanical load. Contractile force generated by the sarcomeres depends on the calcium transient and on the sarcomere length. Stroke work is determined for each segment by simulating the cardiac cycle. Electrical remodeling is simulated by adapting I (Ca,L) kinetics such that a homogeneous distribution of stroke work is obtained. With electrical remodeling, a more homogeneous shortening of the fiber is obtained, while heterogeneity in APD increases and the repolarization wave reverses. Our results are in agreement with experimentally observed homogeneity in mechanics and heterogeneity in electrophysiology. In conclusion, electrical remodeling is a possible mechanism to reduce heterogeneity in cardiomechanics induced by ventricular pacing.
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Kuijpers et al. (2008) studied Cardiac electrical remodeling. Simulated electrical remodeling of ICa,L triggered by mechanical load vs. No remodeling was evaluated on Homogeneity of stroke work and fiber shortening. In a computational model, electrical remodeling of the L-type calcium current driven by mechanoelectric feedback resulted in more homogeneous fiber shortening and increased heterogeneity in action potential duration.
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