Effects and Underlying Mechanisms of Refractory Period Pacing on Repolarization Dynamics in the Human Heart

Diogo Santos1, Michele Orini, Xin Zhou2, Alfonso Bueno-Orovio2, Ben Mark Hanson, Peter Taggart, Martin Hayward, Blanca Rodriguez3, Pier Lambiase

  • 1University College London
  • 2University of Oxford
  • 3Oxford University

Details

Category

Contributed Papers (Oral)

Theme

Cardiovascular and Respiratory Systems Engineering

Sessions

08:00 - 09:30 | Wed 17 Aug | Fantasia L | WeAT8

Cardiac Electrophysiology I

Abstract

Repolarization alternans is related to the initiation of life threatening cardiac arrhythmias. Experimental and computational studies suggest that the abolishment of alternans using dynamic pacing protocols may prevent abnormal heart rhythms. In a recent animal study, refractory period pacing (RPP) on every other beat has shown promising results in alternans reduction. However, the cellular mechanisms underlying this therapy and its efficiency in human patients remain unclear. In this study, in vivo unipolar electrograms acquired during RPP from 240 epicardial sites from one patient were analysed. Current clamp of 18 channels was performed in silico to elucidate the ionic mechanisms underlying action potential modulation by RPP. Its efficacy with positive and negative polarities was tested on a population of 87 calibrated human ventricular models exhibiting alternans. In vivo electrograms showed significant changes in T-wave alternans when applying RPP. In silico, results showed APD shortening for RPP with positive polarity and APD prolongation with RPP negative. Under current clamp protocols, voltage rectification of L-type Ca2+ (ICaL) and inward rectifier K+ (IK1) currents were identified as the key determinants for the observed changes. RPP pacing successfully reduced alternans on the in silico models using a negative polarity stimulus in the short beat.

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