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PAR 1 contribution in acute electrophysiological properties of oral anticoagulants in rabbit pulmonary vein sleeve preparations
Author(s) -
Font Jonaz,
Simeon Mathilda,
Simard Christophe,
Allouche Stéphane,
Plane AnneFlore,
Ferchaud Virginie,
Brionne Marie,
Rouet René,
Nowoczyn Marie,
Manrique Alain,
Puddu Paolo Emilio,
Milliez Paul,
Alexandre Joachim
Publication year - 2018
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12365
Subject(s) - apixaban , dabigatran , effective refractory period , agonist , medicine , atrial fibrillation , pharmacology , rivaroxaban , warfarin , electrophysiology , cardiology , receptor , anesthesia
Abstract Whether oral anticoagulants, vitamin K antagonists ( VKA s), and nonvitamin K oral anticoagulant ( NOAC s) frequently prescribed to atrial fibrillation ( AF ) patients, do themselves have a pro‐ or anti‐arrhythmic effect have never been addressed. Transmembrane action potentials were recorded in an acute rabbit model of superfused pulmonary veins ( PV s) sleeves preparations using standard microelectrode technique. Fluindione 10 μ m ( n = 6) increased the AP (action potential) duration ( APD ), induced a significantly V max depression (from 95 ± 14 to 53 ± 5 V/s, P < 0.05), and 2 : 1 blocks during rapid atrial pacing thus evoking class I anti‐arrhythmic properties, and prevented spontaneous trigger AP s. Apixaban 10 μ m ( n = 6) increased the APD , significantly prolonged the effective refractory period (from 56.3 ± 4.2 to 72.0 ± 8.6 ms, P < 0.05), and prevented triggered AP s occurrence. Fluindione and apixaban effects were suppressed with the addition of the protease‐activated receptors 1 ( PAR 1) agonist SFLLR ‐ NH 2 . Warfarin 10 μ m ( n = 6) significantly abbreviated the early refractory period (from 56.3 ± 4.2 to 45.0 ± 2.2 ms, P < 0.05) and increased triggered AP s occurrence that were successfully prevented by nifedipine but not by the addition of the protease‐activated receptors 1 agonist SFLLR ‐ NH 2 . In this acute rabbit PV s model, VKA s and NOAC s, at physiological concentrations, exhibited very different pharmacological properties that influence PV s electrophysiology, implying PAR 1, with fluindione and apixaban which exhibited more anti‐arrhythmic properties, whereas warfarin exhibited more pro‐arrhythmic properties.