Identification of novel pulmonary vein nodes as generators of ectopic arrhythmic foci for atrial fibrillation: an immunohistochemical proof

Abstract

Introduction:The atrial muscle sleeve (AMS) of the pulmonary vein is the most common source of the arrhythmogenic triggers in atrial fibrillation (AF). Anatomical substrate generating these ectopic currents is still elusive. The present study was designed to study the AMS of pulmonary veins with an emphasis on the structural basis which might govern AF initiation and perpetuation. Materials and Methods:The study was conducted on longitudinal tissue section of pulmonary vein, taken from 15 human cadaveric non-diseased hearts. Tissue was studied histologically using H&E and Gömöri trichrome stain. The pacemaker channels were identified by immunohistochemistry using monoclonal HCN4 and HCN1 antibodies. Results:The AMS was identified in each pulmonary vein, located between the tunica adventitia and tunica media. A node like arrangement of myocytes was seen within the AMS in 30% of veins. It had a compact zone limited by a fibrous capsule and contained much smaller, paler and interconnected myocytes. Outside the capsule there was a zone of dispersed, singly placed myocytes separating the compact zone from the working myocytes of the AMS. HCN4 and HCN1 antibodies were expressed on the cell membrane of nodal myocytes, while the working myocytes demonstrated none to minimal staining. Conclusion:Pulmonary veins nodes are similar to the specialized cardiac conductive tissue in, histological arrangement of compact and transitional zones, cellular characteristics, and the presence of pacemaker channels. They might be the anatomical basis of ectopic arrhythmogenic foci. To our knowledge these nodes are being described for the first time in human.

Exploring the Impact of BKCa Channel Function in Cellular Membranes on Cardiac Electrical Activity

“…This prompts an intriguing hypothesis that cardiac fibroblasts may engage in significant interactions with cardiomyocytes, potentially making a significant contribution to the heart's overall structural and functional integrity (Figure 2). This hypothesis becomes especially pertinent when contemplating the potential augmentation of their numbers or sizes within cardiac tissues, particularly in conditions such as atrial fibrillation or preceding myocardial infarction [22,[28][29][30][31][32]. Atrial fibrillation is a common and often chronic heart rhythm disorder that affects the upper chambers of the heart, known as the atria.…”

“…These occurrences involve brief, selflimiting episodes of membrane hyperpolarization arising from the activation of K V channels, especially BK Ca channels. Therefore, a thorough investigation is thus warranted to determine whether the increased activity of BK Ca channels in vascular smooth muscle cells, especially at the junctions of blood vessels and cardiac tissues such as veins and the atria, or large arteries and the ventricles, might have a potential role in generating ectopic foci and subsequently triggering cardiac arrhythmias in these specific locations [7,22,31,32,43,45,50]. Indeed, earlier reports have identified the source of specific atrial tachycardia, flutter, or fibrillation, with many originating at the interface between the pulmonary veins and the posterior left atrium [51,52].…”

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation

“…Conversely, the ERP of PV cardiomyocytes and left atrial cells both similarly decreased [ 146 ]. Hyperpolarization activates hyperpolarized-activated cyclic nucleotide-gated (HCN) channels [ 147 , 148 ]. The activation of HCN results in a Na + inward current (If or pacemaker current), which is usually specifically located within the sinoatrial node cells.…”