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Effects of Pinacidil on Reentrant Arrhythmias Generated During Acute Regional Ischemia: A Simulation Study

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Abstract

Many experimental studies have pointed out the controversy involving the arrhythmogenic effects of potassium channel openers (KCOs) in ischemia. KCOs activate the ATP-sensitive potassium current [IK(ATP)], resulting in action potential duration (APD) shortening, especially under pathological conditions such as ischemia. Acute myocardial ischemia leads to electrophysiological inhomogeneities in APD, conduction velocity, and refractoriness, which provide the substrate for reentry initiation and maintenance and may lead to malignant arrhythmias. The aim of this work is to analyze the effect of the KCO pinacidil on vulnerability to reentry during acute regional ischemia using computer simulations. We use a two-dimensional virtual heart tissue with implementation of acute regional ischemia conditions. Membrane kinetics are represented by a modified version of Luo–Rudy (phase II) action potential model that incorporates the effect of pinacidil on IK(ATP). The vulnerable window (VW) for reentry is quantified for different doses of pinacidil. Our results show that for doses below 3 μmol/l the VW widens with increasing pinacidil concentration, whereas for higher doses of pinacidil the VW decreases, becoming zero for concentrations above 10 μmol/l. The ionic mechanisms involved in this behavior are explored. This study demonstrates that the effect of pinacidil on arrhythmogenesis is strongly dose-dependent, and that high doses of pinacidil exert a strong antiarrhythmic effect.

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Authors and Affiliations

  1. Centro de Investigación e Innovación en Bioingeniería, Departamento de Ingeniería Electrónica, Universidad Politécnica de Valencia, Camino de Vera s/n, 46022, Valencia, Spain

    Beatriz Trénor, José M. Ferrero Jr. & Fulgencio Montilla

  2. Oxford University Computing Laboratory, Wolfson Building, Parks Road, Oxford, OX1 3QD, UK

    Blanca Rodríguez

  3. Departamento de Ingeniería Electrónica, Universidad Politécnica de Valencia, Camino de Vera s/n, 46022, Valencia, Spain

    José M. Ferrero Jr.

Authors
  1. Beatriz Trénor
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  2. José M. Ferrero Jr.
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  3. Blanca Rodríguez
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  4. Fulgencio Montilla
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Correspondence to José M. Ferrero Jr..

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Trénor, B., Ferrero, J.M., Rodríguez, B. et al. Effects of Pinacidil on Reentrant Arrhythmias Generated During Acute Regional Ischemia: A Simulation Study. Ann Biomed Eng 33, 897–906 (2005). https://doi.org/10.1007/s10439-005-3554-4

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  • DOI: https://doi.org/10.1007/s10439-005-3554-4

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