A Model for Human Action Potential Dynamics In Vivo.

Computational modeling based on experimental data remain important components in cardiac electrophysiological research, especially because clinical data such as human action potential (AP) dynamics are scarce or limited by practical or ethical concerns. Such modeling has been used to develop and test a variety of mechanistic hypotheses, with the majority of these studies involving the rate dependence of action potential duration (APD) and conduction velocity (CV). However, there is very little information regarding the complex dynamics at the boundary of repolarization (or refractoriness) and re-excitability. Here, we developed a 'minimal' ionic model of the human action potential, based on in-vivo human AP recordings obtained during clinical programmed electrical stimulation (PES), to address the progressive decrease in AP take-off potential (TOP) and associated CV slowing seen during tightly spaced extra-stimuli. Recent voltage clamp data demonstrating the effect of intracellular calcium on sodium current availability was incorporated and was required to reproduce large (> 15 mV) elevations in TOP and progressive encroachment. Introducing clinically observed APD gradients into the model enabled us to replicate the dynamic response to PES in patients leading to conduction block and reentry formation for the positive, but not the negative, APD gradient. Finally, we modeled the dynamics of reentry and show that spiral waves follow a meandering trajectory with a period of ~180 ms. We conclude that our model reproduces a variety of electrophysiological behavior including the response to sequential premature stimuli and provides a basis for studies of the initiation of reentry in human ventricular tissue.

• Publication year

  2020

• Venue

  American Journal of Physiology. Heart and Circulatory Physiology

• Publication date

  2020-01-17

• Fields of study

  Medicine, Chemistry, Engineering

• Identifiers
  DOI 10.1152/ajpheart.00557.2019PMID 31951472
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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