Skip to main content
Erschienen in: Surgical and Radiologic Anatomy 1/2022

07.01.2022 | Original Article

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

verfasst von: Tulika Gupta, Mandeep Kaur, Daisy Sahni

Erschienen in: Surgical and Radiologic Anatomy | Ausgabe 1/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

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.

Methods

The study was conducted on a longitudinal tissue section of pulmonary vein, taken from 15 human cadaveric nondiseased 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 the 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.
Literatur
1.
Zurück zum Zitat Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar JG, Badhwar V, Brugada J, Camm J (2018) HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace 20(1):e1–e160CrossRef Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar JG, Badhwar V, Brugada J, Camm J (2018) HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace 20(1):e1–e160CrossRef
2.
Zurück zum Zitat Gao CH, Wang F, Jiang R, Zhang J, Mou H, Yin YH (2011) A region-specific quantitative profile of autonomic innervation of the canine left atrium and pulmonary veins. Auton Neurosci 162:42–47CrossRef Gao CH, Wang F, Jiang R, Zhang J, Mou H, Yin YH (2011) A region-specific quantitative profile of autonomic innervation of the canine left atrium and pulmonary veins. Auton Neurosci 162:42–47CrossRef
3.
Zurück zum Zitat Honjo H, Boyett MR, Niwa R, Inada S, Yamamoto M, Mitsui K, Horiuchi T, Shibata N, Kamiya K, Kodama I (2003) Pacing-induced spontaneous activity in myocardial sleeves of pulmonary veins after treatment with ryanodine. Circ J 107:1937–1943CrossRef Honjo H, Boyett MR, Niwa R, Inada S, Yamamoto M, Mitsui K, Horiuchi T, Shibata N, Kamiya K, Kodama I (2003) Pacing-induced spontaneous activity in myocardial sleeves of pulmonary veins after treatment with ryanodine. Circ J 107:1937–1943CrossRef
4.
Zurück zum Zitat Wang TM, Chiang CE, Sheu JR, Tsou CH, Chang HM, LUK HN (2003) Homogenous distribution of fast response action potentials in canine pulmonary vein sleeves: a contradictory report. Int J Cardiol 89:187–195CrossRef Wang TM, Chiang CE, Sheu JR, Tsou CH, Chang HM, LUK HN (2003) Homogenous distribution of fast response action potentials in canine pulmonary vein sleeves: a contradictory report. Int J Cardiol 89:187–195CrossRef
5.
Zurück zum Zitat Jais P (2000) Dissociation of the venous activity following radiofrequency ablation of pulmonary vein ostia for atrial fibrillation. Circ J 102:II–484 Jais P (2000) Dissociation of the venous activity following radiofrequency ablation of pulmonary vein ostia for atrial fibrillation. Circ J 102:II–484
6.
Zurück zum Zitat Marrouche NF, Cole C, Dresing T, Abdul-Karim A, Bash D, Martin D, Tchou P, Natale A (2002) Response to pharmacologic agents of dissociated pulmonary vein firing initiating atrial fibrillation. J Am Coll Cardiol 39:104CrossRef Marrouche NF, Cole C, Dresing T, Abdul-Karim A, Bash D, Martin D, Tchou P, Natale A (2002) Response to pharmacologic agents of dissociated pulmonary vein firing initiating atrial fibrillation. J Am Coll Cardiol 39:104CrossRef
7.
Zurück zum Zitat Yamane T, Shah DC, Jais P, Haïssaguerre M (2001) Pseudo sinus rhythm originating from the left superior pulmonary vein in a patient with paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 12:1190–1191CrossRef Yamane T, Shah DC, Jais P, Haïssaguerre M (2001) Pseudo sinus rhythm originating from the left superior pulmonary vein in a patient with paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 12:1190–1191CrossRef
8.
Zurück zum Zitat Gupta T, Randhawa A, Sahni D (2020) Histological evaluation of atrial muscle sleeve of pulmonary veins as relevant to trigger mapping and ablation. Surg Radiol Anat 42:1271–1277CrossRef Gupta T, Randhawa A, Sahni D (2020) Histological evaluation of atrial muscle sleeve of pulmonary veins as relevant to trigger mapping and ablation. Surg Radiol Anat 42:1271–1277CrossRef
9.
Zurück zum Zitat Perez-Lugones A, Mcmahon JT, Ratliff NB, Saliba WI, Schweikert RA, Marrouche NF, Saad EB, Navia JL, Mccarthy PM, Tchou P (2003) Evidence of specialized conduction cells in human pulmonary veins of patients with atrial fibrillation. J Cardiovasc Electrophysiol 14:803–809CrossRef Perez-Lugones A, Mcmahon JT, Ratliff NB, Saliba WI, Schweikert RA, Marrouche NF, Saad EB, Navia JL, Mccarthy PM, Tchou P (2003) Evidence of specialized conduction cells in human pulmonary veins of patients with atrial fibrillation. J Cardiovasc Electrophysiol 14:803–809CrossRef
10.
Zurück zum Zitat Larsson HP (2010) How is the heart rate regulated in the sinoatrial node? Another piece to the puzzle. J Gen Physiol 136:237–241CrossRef Larsson HP (2010) How is the heart rate regulated in the sinoatrial node? Another piece to the puzzle. J Gen Physiol 136:237–241CrossRef
11.
Zurück zum Zitat Nguyen BL, Fishbein MC, Chen LS, Chen PS, Masroor S (2009) Histopathological substrate for chronic atrial fibrillation in humans. Heart Rhythm 6:454–460CrossRef Nguyen BL, Fishbein MC, Chen LS, Chen PS, Masroor S (2009) Histopathological substrate for chronic atrial fibrillation in humans. Heart Rhythm 6:454–460CrossRef
12.
Zurück zum Zitat Difrancesco D (2010) The role of the funny current in pacemaker activity. Circ Res 106:434–446CrossRef Difrancesco D (2010) The role of the funny current in pacemaker activity. Circ Res 106:434–446CrossRef
13.
Zurück zum Zitat Mitrofanova LB, Gorshkov AN, Lebedev DS, Mikhaylov EN (2014) Evidence of specialized tissue in human interatrial septum: histological, immunohistochemical and ultrastructural findings. PLoS ONE 9:e113343CrossRef Mitrofanova LB, Gorshkov AN, Lebedev DS, Mikhaylov EN (2014) Evidence of specialized tissue in human interatrial septum: histological, immunohistochemical and ultrastructural findings. PLoS ONE 9:e113343CrossRef
14.
Zurück zum Zitat Anderson RH, Spicer DE, Mori S (2016) Of tracts, rings, nodes, cusps, sinuses, and arrhythmias—a comment on Szili-Torok et al.’s paper entitled. The dead-end tract and its role in arrhythmogenesis. J Cardiovasc Dev Dis 3:11CrossRef Anderson RH, Spicer DE, Mori S (2016) Of tracts, rings, nodes, cusps, sinuses, and arrhythmias—a comment on Szili-Torok et al.’s paper entitled. The dead-end tract and its role in arrhythmogenesis. J Cardiovasc Dev Dis 3:11CrossRef
15.
Zurück zum Zitat Aschoff L (1910) Referat uber die Herzstorungen in ihren Beziehungen zu den Spezifischen Muskelsystem des Herzens. Verh Dtsch Pathol Ges 14:3 (Ep Europace 20:e1-e160.35) Aschoff L (1910) Referat uber die Herzstorungen in ihren Beziehungen zu den Spezifischen Muskelsystem des Herzens. Verh Dtsch Pathol Ges 14:3 (Ep Europace 20:e1-e160.35)
16.
Zurück zum Zitat Monckeberg J (1910) Beitrage zur normalen und pathologischen Anatomie des Herzens. Verh Dtsch Pathol Ges 14:64–71 Monckeberg J (1910) Beitrage zur normalen und pathologischen Anatomie des Herzens. Verh Dtsch Pathol Ges 14:64–71
17.
Zurück zum Zitat Randhawa A, Gupta T, Aggarwal A, Sahni D, Singh RS (2017) Histological topography of the atrioventricular node and its extensions in relation to the cardiothoracic surgical landmarks in normal human hearts. Cardiovasc Pathol 30:38–44CrossRef Randhawa A, Gupta T, Aggarwal A, Sahni D, Singh RS (2017) Histological topography of the atrioventricular node and its extensions in relation to the cardiothoracic surgical landmarks in normal human hearts. Cardiovasc Pathol 30:38–44CrossRef
18.
Zurück zum Zitat Vassall-Adams P (1983) Ultrastructure of the human atrio ventricular conduction tissues. Eur Heart J 4:449–460CrossRef Vassall-Adams P (1983) Ultrastructure of the human atrio ventricular conduction tissues. Eur Heart J 4:449–460CrossRef
19.
Zurück zum Zitat Waller B, Gering L, Branyas N, Slack J (1993) Anatomy, histology, and pathology of the cardiac conduction system: part I. Clin Cardiol 16:249–252CrossRef Waller B, Gering L, Branyas N, Slack J (1993) Anatomy, histology, and pathology of the cardiac conduction system: part I. Clin Cardiol 16:249–252CrossRef
20.
Zurück zum Zitat Ross MH, Pawlina W (2011) Histology: a text and atlas: with correlated cell and molecular biology. Wolters Kluwer/Lippincott Williams & Wilkins Health, Philadelphia Ross MH, Pawlina W (2011) Histology: a text and atlas: with correlated cell and molecular biology. Wolters Kluwer/Lippincott Williams & Wilkins Health, Philadelphia
21.
Zurück zum Zitat Rossi L (1980) Histopathology of cardiac arrhythmias. Ann Intern Med 93:384–384 Rossi L (1980) Histopathology of cardiac arrhythmias. Ann Intern Med 93:384–384
22.
Zurück zum Zitat Masani F (1986) Node-like cells in the myocardial layer of the pulmonary vein of rats: an ultrastructural study. J Anat 145:133PubMedPubMedCentral Masani F (1986) Node-like cells in the myocardial layer of the pulmonary vein of rats: an ultrastructural study. J Anat 145:133PubMedPubMedCentral
23.
Zurück zum Zitat Kholová I, Kautzner J (2003) Anatomic characteristics of extensions of atrial myocardium into the pulmonary veins in subjects with and without atrial fibrillation. Pacing Clin Electrophysiol 26:1348–1355CrossRef Kholová I, Kautzner J (2003) Anatomic characteristics of extensions of atrial myocardium into the pulmonary veins in subjects with and without atrial fibrillation. Pacing Clin Electrophysiol 26:1348–1355CrossRef
24.
Zurück zum Zitat Saito T, Waki K, Becker AE (2000) Left atrial myocardial extension onto pulmonary veins in humans: anatomic observations relevant for atrial arrhythmias. J Cardiovasc Electrophysiol 11:888–894CrossRef Saito T, Waki K, Becker AE (2000) Left atrial myocardial extension onto pulmonary veins in humans: anatomic observations relevant for atrial arrhythmias. J Cardiovasc Electrophysiol 11:888–894CrossRef
25.
Zurück zum Zitat Tagawa M, Higuchi K, Chinushi M, Washizuka T, Ushiki T, Ishihara N (2001) Myocardium extending from the left atrium onto the pulmonary veins: a comparison between subjects with and without atrial fibrillation. Pacing Clin Electrophysiol 24:1459–1463CrossRef Tagawa M, Higuchi K, Chinushi M, Washizuka T, Ushiki T, Ishihara N (2001) Myocardium extending from the left atrium onto the pulmonary veins: a comparison between subjects with and without atrial fibrillation. Pacing Clin Electrophysiol 24:1459–1463CrossRef
26.
Zurück zum Zitat Li YD, Hong YF, Zhang Y, Zhou XH, Ji YT, Li HL, Xu GJ, Li JX, Sun L, Zhang JH (2014) Association between reversal in the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel and age-related atrial fibrillation. Med Sci Mon Int Med J Exp Clin Res 20:2292 Li YD, Hong YF, Zhang Y, Zhou XH, Ji YT, Li HL, Xu GJ, Li JX, Sun L, Zhang JH (2014) Association between reversal in the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel and age-related atrial fibrillation. Med Sci Mon Int Med J Exp Clin Res 20:2292
27.
Zurück zum Zitat Li N, Csepe TA, Hansen BJ, Dobrzynski H, Higgins RS, Kilic A, Mohler PJ, Janssen PM, Rosen MR, Biesiadecki BJ (2015) Molecular mapping of sinoatrial node HCN channel expression in the human heart. Circ Arrhythm Electrophysiol 8:1219–1227CrossRef Li N, Csepe TA, Hansen BJ, Dobrzynski H, Higgins RS, Kilic A, Mohler PJ, Janssen PM, Rosen MR, Biesiadecki BJ (2015) Molecular mapping of sinoatrial node HCN channel expression in the human heart. Circ Arrhythm Electrophysiol 8:1219–1227CrossRef
28.
Zurück zum Zitat Lubitz SA, Yi BA, Ellinor PT (2009) Genetics of atrial fibrillation. Cardiol Clin 27:25–33CrossRef Lubitz SA, Yi BA, Ellinor PT (2009) Genetics of atrial fibrillation. Cardiol Clin 27:25–33CrossRef
29.
Zurück zum Zitat Li JY, Wang HJ, Xu B, Wang XP, Fu YC, Chen MY, Zhang DX, Liu Y, Xue Q, Li Y (2012) Hyperpolarization activated cation current (If) in cardiac myocytes from pulmonary vein sleeves in the canine with atrial fibrillation. J Geriatr Cardiol 9:366PubMedPubMedCentral Li JY, Wang HJ, Xu B, Wang XP, Fu YC, Chen MY, Zhang DX, Liu Y, Xue Q, Li Y (2012) Hyperpolarization activated cation current (If) in cardiac myocytes from pulmonary vein sleeves in the canine with atrial fibrillation. J Geriatr Cardiol 9:366PubMedPubMedCentral
30.
Zurück zum Zitat Schoenwolf GC, Bleyl SB, Brauer PR, Francis-West PH (2015) Larsen’s human embryology. Elsevier, Philadelphia Schoenwolf GC, Bleyl SB, Brauer PR, Francis-West PH (2015) Larsen’s human embryology. Elsevier, Philadelphia
31.
Zurück zum Zitat Jongbloed MR, Schalij MJ, Poelmann RE, Blom NA, Fekkes ML, Wang Z, Fishman GI, Gittenberger-De Groot AC (2004) Embryonic conduction tissue: a spatial correlation with adult arrhythmogenic areas. J Cardiovasc Electrophysiol 15:349–355CrossRef Jongbloed MR, Schalij MJ, Poelmann RE, Blom NA, Fekkes ML, Wang Z, Fishman GI, Gittenberger-De Groot AC (2004) Embryonic conduction tissue: a spatial correlation with adult arrhythmogenic areas. J Cardiovasc Electrophysiol 15:349–355CrossRef
32.
Zurück zum Zitat Tan AY, Li H, Wachsmann-Hogiu S, Chen LS, Chen PS, Fishbein MC (2006) Autonomic innervation and segmental muscular disconnections at the human pulmonary vein-atrial junction: implications for catheter ablation of atrial-pulmonary vein junction. J Am Coll Cardiol 48:132–143CrossRef Tan AY, Li H, Wachsmann-Hogiu S, Chen LS, Chen PS, Fishbein MC (2006) Autonomic innervation and segmental muscular disconnections at the human pulmonary vein-atrial junction: implications for catheter ablation of atrial-pulmonary vein junction. J Am Coll Cardiol 48:132–143CrossRef
33.
Zurück zum Zitat Kirklin/Barratt B (1993) Cardiac surgery: morphology, diagnostic criteria, natural history, techniques, results, and indications, pp. 15–17 Kirklin/Barratt B (1993) Cardiac surgery: morphology, diagnostic criteria, natural history, techniques, results, and indications, pp. 15–17
Metadaten
Titel
Identification of novel pulmonary vein nodes as generators of ectopic arrhythmic foci for atrial fibrillation: an immunohistochemical proof
verfasst von
Tulika Gupta
Mandeep Kaur
Daisy Sahni
Publikationsdatum
07.01.2022
Verlag
Springer Paris
Erschienen in
Surgical and Radiologic Anatomy / Ausgabe 1/2022
Print ISSN: 0930-1038
Elektronische ISSN: 1279-8517
DOI
https://doi.org/10.1007/s00276-021-02864-w

Weitere Artikel der Ausgabe 1/2022

Surgical and Radiologic Anatomy 1/2022 Zur Ausgabe

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

S3-Leitlinie zu Pankreaskrebs aktualisiert

23.04.2024 Pankreaskarzinom Nachrichten

Die Empfehlungen zur Therapie des Pankreaskarzinoms wurden um zwei Off-Label-Anwendungen erweitert. Und auch im Bereich der Früherkennung gibt es Aktualisierungen.

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

18.04.2024 Pädiatrische Notfallmedizin Nachrichten

Im Choosing-Wisely-Programm, das für die deutsche Initiative „Klug entscheiden“ Pate gestanden hat, sind erstmals Empfehlungen zum Umgang mit Notfällen von Kindern erschienen. Fünf Dinge gilt es demnach zu vermeiden.

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.