Ectopic activity in the rat pulmonary vein can arise from simultaneous activation of alpha1- and beta1-adrenoceptors.
OBJECTIVE
Atrial fibrillation (AF) is the most common electrical cardiac disorder in clinical practice. The major trigger for AF is focal ectopic activity of unknown origin in sleeves of cardiac muscle that extend into the pulmonary veins. We examined the role of noradrenaline in the genesis of ectopic activity in the pulmonary vein.


METHODS
Mechanical activity of strips of pulmonary vein isolated from male Wistar rats was recorded via an isometric tension meter. Twitch contractions of cardiac myocytes were evoked by electrical field stimulation in a tissue bath through which flowed Krebs-Heinseleit solution warmed to 36-37 degrees C and gassed with 95% O(2) 5% CO(2).


RESULTS
The superfusion of noradrenaline induced ectopic contractions in 71 of 76 different isolated pulmonary veins. Ectopic contractions in the pulmonary vein were not associated with electrically evoked twitch contractions. The effect of noradrenaline on the pulmonary vein could be replicated by the simultaneous, but not separate, application of the alpha adrenoceptor agonist phenylephrine and the beta adrenoceptor agonist isoprenaline. The use of selective agonists and antagonists for adrenoceptor subtypes showed that ectopic activity in the pulmonary vein arose from the simultaneous stimulation of alpha(1) and beta(1) adrenoceptors. The application of noradrenaline to isolated strips of left atrium did not induce ectopic contractions (n=10). conclusions: These findings suggest an origin for ectopic activity in the pulmonary vein that requires activation of both alpha and beta adrenoceptors. They also open new perspectives towards our understanding of the triggering of AF.
Maupoil
V
V
CNRS UMR 6542, Faculté des Sciences, Université François-Rabelais de Tours, Tours, France.
Bronquard
C
C
Freslon
J-L
JL
Cosnay
P
P
Findlay
I
I
D000818:Animals; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011667:Pulmonary Veins / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D018340:Receptors, Adrenergic, alpha-1; D018342:Receptors, Adrenergic, beta-1; D014662:Vasoconstrictor Agents; D009638:Norepinephrine