Electrophysiological and haemodynamic effects of vernakalant and flecainide in dyssynchronous canine hearts.
OBJECTIVE
About one-third of patients with mild dyssynchronous heart failure suffer from atrial fibrillation (AF). Drugs that convert AF to sinus rhythm may further slowdown ventricular conduction. We aimed to investigate the electrophysiological and haemodynamic effects of vernakalant and flecainide in a canine model of chronic left bundle branch block (LBBB).


RESULTS
Left bundle branch block was induced in 12 canines. Four months later, vernakalant or flecainide was administered using a regime, designed to achieve clinically used plasma concentrations of the drugs, n = 6 for each drug. Epicardial electrical contact mapping showed that both drugs uniformly prolonged myocardial conduction time. Vernakalant increased QRS width significantly less than flecainide (17 ± 13 vs. 34 ± 15%, respectively). Nevertheless, both drugs equally decreased LVdP/dtmax by ∼15%, LVdP/dtmin by ∼10%, and left ventricular systolic blood pressure by ∼5% (P = n.s. between drugs).


CONCLUSIONS
Vernakalant prolongs ventricular conduction less than flecainide, but both drugs had a similar, moderate negative effect on ventricular contractility and relaxation. Part of these reductions seems to be related to the increase in dyssynchrony.
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, Limburg, The Netherlands Department of Cardiothoracic Surgery, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Limburg, The Netherlands L.vanmiddendorp@maastrichtuniversity.nl.
Lars B
LB
van Middendorp
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, Limburg, The Netherlands.
Marc
M
Strik
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, Limburg, The Netherlands.
Patrick
P
Houthuizen
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, Limburg, The Netherlands.
Marion
M
Kuiper
Department of Cardiothoracic Surgery, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Limburg, The Netherlands.
Jos G
JG
Maessen
Division of Cardiology, Fondazione Cardiocentro Ticino, Via Tesserete 48, CH-6900 Lugano, Switzerland.
Angelo
A
Auricchio
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, Limburg, The Netherlands.
Frits W
FW
Prinzen
D000200:Action Potentials; D000818:Animals; D000840:Anisoles / Q000097:blood / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002037:Bundle-Branch Block / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004285:Dogs; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D005424:Flecainide / Q000097:blood / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011759:Pyrrolidines / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D000840:Anisoles; D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; C524581:vernakalant; D005424:Flecainide
Atrial fibrillation; Canine; Dyssynchrony; Epicardial electrical activation mapping; Flecainide; Left bundle branch block; Vernakalant