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      Decreased connexin 43 and increased fibrosis in atrial regions susceptible to complex fractionated atrial electrograms.

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          Abstract

          Complex fractionated atrial electrograms (CFAE) is distributed at preferential sites of atrium, and the mechanism underlying CFAE is not fully understood. We hypothesized that preexisting atrial abnormalities may be involved in the formation of CFAE.

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          Remodelling of gap junctions and connexin expression in diseased myocardium

          Nicholas J. Severs, Alexandra Bruce, Emmanuel Dupont … (2008)
          Gap junctions form the cell-to-cell pathways for propagation of the precisely orchestrated patterns of current flow that govern the regular rhythm of the healthy heart. As in most tissues and organs, multiple connexin types are expressed in the heart: connexin43 (Cx43), Cx40 and Cx45 are found in distinctive combinations and relative quantities in different, functionally-specialized subsets of cardiac myocyte. Mutations in genes that encode connexins have only rarely been identified as being a cause of human cardiac disease, but remodelling of connexin expression and gap junction organization are well documented in acquired adult heart disease, notably ischaemic heart disease and heart failure. Remodelling may take the form of alterations in (i) the distribution of gap junctions and (ii) the amount and type of connexins expressed. Heterogeneous reduction in Cx43 expression and disordering in gap junction distribution feature in human ventricular disease and correlate with electrophysiologically identified arrhythmic changes and contractile dysfunction in animal models. Disease-related alterations in Cx45 and Cx40 expression have also been reported, and some of the functional implications of these are beginning to emerge. Apart from ventricular disease, various features of gap junction organization and connexin expression have been implicated in the initiation and persistence of the most common form of atrial arrhythmia, atrial fibrillation, though the disparate findings in this area remain to be clarified. Other major tasks ahead focus on the Purkinje/working ventricular myocyte interface and its role in normal and abnormal impulse propagation, connexin-interacting proteins and their regulatory functions, and on defining the precise functional properties conferred by the distinctive connexin co-expression patterns of different myocyte types in health and disease.
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            Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation.

            Radmira Greenstein, Sohail Hassan, Mehmet Ozaydin … (2002)
            The pulmonary veins (PVs) have been demonstrated to often play an important role in generating atrial fibrillation (AF). The purpose of this study was to determine the safety and efficacy of segmental PV isolation in patients with paroxysmal or persistent AF. In 70 consecutive patients (mean age, 53 +/- 11 years) with paroxysmal (58) or persistent (12) AF, segmental PV isolation guided by ostial PV potentials was performed. The left superior, left inferior, and right superior PVs were targeted for isolation in all patients, and the right inferior PV was isolated in 20 patients. Among the 230 targeted PVs, 217 (94%) were completely isolated, with a mean of 6.5 +/- 4.2 minutes of radiofrequency energy applied at a maximum power setting of 35 W. A second PV isolation procedure was performed in 6 patients (9%). At 5 months of follow-up, 70% of patients with paroxysmal and 22% of patients with persistent AF were free from recurrent AF (P 80% of patients with paroxysmal AF. The clinical efficacy of pulmonary vein isolation is much lower when AF is persistent than when it is paroxysmal.
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              Chamber-related differences in connexin expression in the human heart.

              N Severs, Esther Dupont-Versteegden, C Vozzi … (1999)
              Electrical coupling in the heart is mediated by gap junctions, aggregates of cell-to-cell channels composed of connexins. The principal cardiac gap-junctional connexin, connexin43 (Cx43), is reduced in diseased human myocardium that is prone to arrhythmia. Three additional connexin isoforms, Cx40, Cx45 and Cx37, of distinctive functional capacities in vitro, are expressed in cardiovascular cells, but our knowledge of their expression patterns in the human heart is fragmentary. In the present study, we therefore applied Northern blotting, Western blotting and immunoconfocal microscopy to analyse and compare the expression of Cx43, Cx40, Cx37 and Cx45 mRNA and protein in the human left ventricle, right ventricle, left atrium and right atrium of the human heart. Cx43 was confirmed to be abundantly expressed at similar levels by myocytes in all four chambers. Cx40 levels varied between chambers in the order right atrium >left atrium >/= right ventricle approximately left ventricle. Cx37 (exclusively expressed in the endothelium) was expressed at similar overall levels in all chambers (as judged from Northern blots). Cx45 was detectable only at very low levels, with a trend toward higher levels in the atria than the ventricles in a pattern similar to Cx40. The results indicate that in humans, the ventricles and atria have distinctive connexin expression profiles, and that the atrial-type connexin profile is more pronounced in the right atrium than the left atrium. While the ventricular connexin expression pattern resembles that of other mammalian species, atrial connexin expression shows greater species variation. These differences contribute to the interpretative framework for examining the potential role of altered connexin expression in ventricular and atrial arrhythmia in the human heart. Copyright 1999 Academic Press.
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                Author and article information

                Journal
                Journal ID (iso-abbrev): Cardiology
                Title: Cardiology
                ISSN (Electronic): 1421-9751
                ISSN (Print): 0008-6312
                Publication date (Electronic): 2009
                Volume: 114
                Issue: 1
                Affiliations
                [1 ] Department of Cardiology, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai 200030, China. xkliuxu@126.com
                Article
                Publisher Item ID: 000210398
                DOI: 10.1159/000210398
                PubMed ID: 19342855
                SO-VID: 12094643-ed90-4173-9b46-850a3d9fa4cd
                Copyright © Copyright 2009 S. Karger AG, Basel.
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