The local repolarization heterogeneity in the murine pulmonary veins myocardium contributes to the spatial distribution of the adrenergically induced ectopic foci

Abstract

An atrial tachyarrhythmias is predominantly triggered by a proarrhythmic activity originate from the pulmonary veins (PV) myocardial sleeves; sympathetic or adrenergic stimulation facilitates PV proarrhythmia. In the present study the electrophysiological inhomogeneity, spatiotemporal characteristics of the adrenergically induced ectopic firing and sympathetic nerves distribution have been investigated in a murine PV myocardium to clarify mechanisms of adrenergic PV ectopy. Electrically paced murine PV demonstrate atrial-like pattern of conduction and atrial-like action potentials (AP) with longest duration in the mouth of PV. The application of norepinephrine (NE), agonists of α-and β-adrenergic receptors (ARs) or intracardiac nerves stimulation induced spontaneous AP in a form of periodical bursts or continuous firing. NE-or ARs agonists-induced SAP originated from unifocal ectopic foci with predominant localization in the region surrounding PV mouth, but not in the distal portions of a murine PV myocardium. A higher level of catecholamine content and catecholamine fiber network density was revealed in the PV myocardial sleeves relative to LA appendage. However, no significant local variation of catecholamine content and fiber density was observed in the murine PV. In conclusion, PV mouth region appear to be a most susceptible to adrenergic proarrhythmia in mice. Intrinsic spatial heterogeneity of AP duration can be considered as a factor influencing localization of the ectopic foci in PV.

Attenuation of inward rectifier potassium current contributes to the α1‐adrenergic receptor‐induced proarrhythmicity in the caval vein myocardium

“…Notably, our previous study demonstrated that application of α 1 ‐adrenomimetics was unable to induce RMP depolarization in murine PV myocardium 53 . In addition, in another study, I K1 current remained unchanged under α 1 ‐stimulation in isolated canine caval veins cardiomyocytes 26 .…”

“…Notably, our previous study demonstrated that application of α 1 -adrenomimetics was unable to induce RMP depolarization in murine PV myocardium. 53 In addition, in another study, I K1 current remained unchanged under α 1 -stimulation in isolated canine caval veins cardiomyocytes. 26 The species-specific channel-forming Kir2.x composition might underlie insensibility of this current to α1-adrenomimetics in mice and dogs 35 and sensitivity of I K1 in rats.…”

Automatic Activity Arising in Cardiac Muscle Sleeves of the Pulmonary Vein

“…In quiescent mouse PV [ 30 , 35 ], NE also induced automatic activity that appeared in the different forms (continuous or bursts of AP) already observed in spontaneously active preparations under basal conditions ( Section 5.1 ). NE was without effect on the LA.…”

“…The latter is consistent with human observation: nerve filaments and ganglia are located in the adventitia [ 29 ]. In the mouse, catecholamine fibers were concentrated in the PV rather than in the LA appendage [ 30 ]. In the rat, the density of catecholamine fibers in the PV increased with post-natal age [ 31 ].…”

“…NE was without effect on the LA. However, Potekhina et al [ 30 ] showed that automatic activity could also be evoked by isoprenaline or phenylephrine alone, which seems to be clearly a species-specific feature. Both substances caused hyperpolarization of the PV membrane potential.…”