Effects of antiarrhythmic drug therapy on atrioventricular nodal function during atrial fibrillation in humans.
OBJECTIVE
To assess the effects of metoprolol and amiodarone on atrial and ventricular activity during atrial fibrillation (AF) in post-surgical patients, and to develop and use a mathematical model of the atrioventricular (AV) node during AF that incorporates parameters describing the properties of the AV node to evaluate the physiological basis of the drug effects.


RESULTS
Ten post-surgical patients were evaluated where three received no medical therapy, three received metoprolol, three received amiodarone, and one received both metoprolol and amiodarone. The medications led to increases of 37-310 ms in the mean VV interval in treated patients, but much smaller changes in the mean AA intervals in the right and left atria. The mathematical model incorporating a random influence of the concealed conduction parameter was capable of reproducing the histograms of the VV intervals based on the input from the right atrium by systematically searching parameter space.


CONCLUSIONS
Changes in the ventricular rate are mainly due to the alteration in the AV nodal properties rather than changes in the atrial rhythm. The medications can display differential effects on the physiological properties of the AV node, and therefore the mathematical model may help to identify novel pharmacological targets.
Mangin
Laurence
L
Département de Physiologie-Explorations Fonctionnelles, CHU Bichat, Université Paris VII, France.
Vinet
Alain
A
Pagé
Pierre
P
Glass
Leon
L
D000368:Aged; D000638:Amiodarone / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D001283:Atrioventricular Node / Q000187:drug effects* / Q000503:physiopathology; D003198:Computer Simulation; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008433:Mathematics; D008790:Metoprolol / Q000494:pharmacology*; D008875:Middle Aged
D000889:Anti-Arrhythmia Agents; D008790:Metoprolol; D000638:Amiodarone