Ectopic activity in the rat pulmonary vein can arise from simultaneous activation of α₁‐ and β₁‐adrenoceptors

Abstract

Background and purpose: 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. Experimental approach: 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 36-371C and gassed with 95% O 2 5% CO 2 . Key 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 a adrenoceptor agonist phenylephrine and the b 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 a 1 and b 1 adrenoceptors. The application of noradrenaline to isolated strips of left atrium did not induce ectopic contractions (n ¼ 10). Conclusions: These findings suggest an origin for ectopic activity in the pulmonary vein that requires activation of both a and b adrenoceptors. They also open new perspectives towards our understanding of the triggering of AF.

Catecholaminergic automatic activity in the rat pulmonary vein: electrophysiological differences between cardiac muscle in the left atrium and pulmonary vein

“…3B) also stopped automatic activity, and in this case the membrane potential depolarized to Ϫ38 Ϯ 2 mV (n ϭ 4). This extends our previous observation that inhibition of either ␣-or ␤-adrenergic receptors stops automatic activity induced by norepinephrine in the pulmonary vein (20).…”

“…There was little difference between the action potentials evoked by electrical stimulation (2 Hz) in cardiac muscle of the pulmonary vein and the left atrium. In the pulmonary vein, the diastolic membrane potential was Ϫ84 Ϯ 1 mV (n ϭ 51 penetrations in 7 preparations), action potential amplitude 99 Ϯ 1 mV, maximum rate of phase 0 depolarization 190 Ϯ 6 V/s, APD 20 1 ms, and APD 90 43 Ϯ 1 ms. In the left atrium, the diastolic membrane potential was Ϫ84 Ϯ 1 mV (n ϭ 92 penetrations in 10 preparations), action potential amplitude 106 Ϯ 1 mV, maximum rate of phase 0 depolarization 196 Ϯ 5 V/s, APD 20 3 Ϯ 1 ms, and APD 90 36 Ϯ 1 ms.…”

“…Action potential duration was measured at 20 and 90% of the repolarization (APD 20 and APD90, respectively). Membrane potential recordings were analyzed by measuring the resting membrane potential at 1-s intervals.…”

“…In our laboratory, we have never observed spontaneous activity in isolated pulmonary veins of the rat under basal physiological conditions. On the other hand, we recently showed that automatic contractile activity can be induced in pulmonary veins but not in the left atrium by the application of the catecholamine norepinephrine (20). Therefore, the objective of this study was to determine the effect of catecholaminergic stimulation on the membrane potential and to characterize automatic activity in cardiac muscle of the pulmonary vein of the rat.…”

Electrophysiological and Pharmacological Properties of the Pulmonary Vein Myocardium

“…Pharmacological analyses revealed that hyperpolarization and depolarization were mediated by β-and α-adrenergic receptors, respectively, and that simultaneous activation of both receptor types are necessary for the generation of automatic activity. 22,26,39) In case of the mouse pulmonary vein myocardium, 23) application of noradrenaline to quiescent preparations induced automatic activity (Fig. 1C), which were often preceded by hyperpolarization or depolarization of the resting membrane potential.…”