scholarly journals Do M-cells contribute significantly in T-wave morphology during normal and arrhythmogenesis conditions like short QT Syndrome?

2020 ◽  
Author(s):  
Ponnuraj Kirthi Priya ◽  
Srinivasan Jayaraman

AbstractAimsThis paper proposes to explain the mechanism of M-cells, particularly its role in the T-wave generation and its contribution to arrhythmogenesis in short QT syndrome 2 (SQTS2).MethodsA 2D transmural anisotropic ventricular model made up of three principal cell types were developed. Different setups in which: a) entire column of mid-myocardial (mid) cells, b) single island of cells c) two island of cells within the mid-layer d) single island of cells in endocardial (endo)-mid layer were considered as M-cells. These setups are stimulated to explain i) contribution of M-cells in T-wave morphology ii) arrhythmia generation phenomena under SQTS2 heterozygous gene mutation by creating pseudo ECGs from the tissue.ResultsFindings infer that setups with an entire layer of M-cells and a higher percentage of epicardial (epi) cells exhibit positive T-waves. Increasing the size of the island in M-cell island setups results in an increased positive T-peak. Placing the M-cell island in the bottom of the mid-layer produced low amplitude T-waves. Further, in two M-cell islands setup, a higher T-wave amplitude was observed when the islands are placed closer than far apart. Moving the M-cell island slightly into the endo layer increases the amplitude of the T-wave. Lastly, on including SQTS2 conditions and pacing with premature beats, an arrhythmia occurs only in those setups containing a layer of M-cells compared to M-cells island setup.ConclusionThese simulation findings paved the way for a better understanding of the M-cells functionality in T-wave morphology as well as promoting arrhythmogenesis under SQTS2 condition.

2009 ◽  
Vol 14 (3) ◽  
pp. 262-267 ◽  
Author(s):  
Olli Anttonen ◽  
Juhani Junttila ◽  
Carla Giustetto ◽  
Fiorenzo Gaita ◽  
Eeva Linna ◽  
...  

2011 ◽  
Vol 301 (1) ◽  
pp. H200-H208 ◽  
Author(s):  
Jun-ichi Okada ◽  
Takumi Washio ◽  
Akiko Maehara ◽  
Shin-ichi Momomura ◽  
Seiryo Sugiura ◽  
...  

The cellular basis of the T-wave morphology of surface ECG remains controversial in clinical cardiology. We examined the effect of action potential duration (APD) distribution on T-wave morphology using a realistic model of the human ventricle and torso. We developed a finite-element model of the ventricle consisting of ∼26 million elements, including the conduction system, each implemented with the ion current model of cardiomyocytes. This model was embedded in a torso model with distinct organ structures to obtain the standard ECG leads. The APD distribution was changed in the transmural direction by locating the M cells in either the endocardial or epicardial region. We also introduced apicobasal gradients by modifying the ion channel parameters. Both the transmural gradient (with M cells on the endocardial side) and the apicobasal gradient produced positive T waves, although a very large gradient was required for the apicobasal gradient. By contrast, T waves obtained with the transmural gradient were highly symmetric and, therefore, did not represent the true physiological state. Only combination of the transmural and the moderate apicobasal gradients produced physiological T waves in surface ECG. Positive T waves in surface ECG mainly originated from the transmural distribution of APD with M cells on the endocardial side, although the apicobasal gradient was also required to attain the physiological waveform.


EP Europace ◽  
2018 ◽  
Vol 20 (suppl_3) ◽  
pp. iii113-iii119 ◽  
Author(s):  
Ben J M Hermans ◽  
Job Stoks ◽  
Frank C Bennis ◽  
Arja S Vink ◽  
Ainara Garde ◽  
...  

Heart Rhythm ◽  
2018 ◽  
Vol 15 (6) ◽  
pp. 860-869 ◽  
Author(s):  
Nobuhiro Takasugi ◽  
Mieko Takasugi ◽  
Hiroko Goto ◽  
Takashi Kuwahara ◽  
Takashi Nakashima ◽  
...  

EP Europace ◽  
2019 ◽  
Vol 21 (11) ◽  
pp. 1725-1732 ◽  
Author(s):  
Greg J Mellor ◽  
Pankaj Panwar ◽  
Andrea K Lee ◽  
Christian Steinberg ◽  
Julie A Hathaway ◽  
...  

Abstract Aims Pathogenic gain-of-function variants in CACAN1C cause type-8 long QT syndrome (LQT8). We sought to describe the electrocardiographic features in LQT8 and utilize molecular modelling to gain mechanistic insights into its genetic culprits. Methods and results Rare variants in CACNA1C were identified from genetic testing laboratories. Treating physicians provided clinical information. Variant pathogenicity was independently assessed according to recent guidelines. Pathogenic (P) and likely pathogenic (LP) variants were mapped onto a 3D modelled structure of the Cav1.2 protein. Nine P/LP variants, identified in 23 patients from 19 families with non-syndromic LQTS were identified. Six variants, found in 79% of families, clustered to a 4-residue section in the cytosolic II–III loop region which forms a region capable of binding STAC SH3 domains. Therefore, variants may affect binding of SH3-domain containing proteins. Arrhythmic events occurred in similar proportions of patients with II–III loop variants and with other P/LP variants (53% vs. 48%, P = 0.41) despite shorter QTc intervals (477 ± 31 ms vs. 515 ± 37 ms, P = 0.03). A history of sudden death was reported only in families with II–III loop variants (60% vs. 0%, P = 0.03). The predominant T-wave morphology was a late peaking T wave with a steep descending limb. Exercise testing demonstrated QTc prolongation on standing and at 4 min recovery after exercise. Conclusion The majority of P/LP variants in patients with CACNA1C-mediated LQT8 cluster in an SH3-binding domain of the cytosolic II–III loop. This represents a ‘mutation hotspot’ in LQT8. A late-peaking T wave with a steep descending limb and QT prolongation on exercise are commonly seen.


Author(s):  
Grażyna Markiewicz-Łoskot ◽  
Ewelina Kolarczyk ◽  
Bogusław Mazurek ◽  
Marianna Łoskot ◽  
Lesław Szydłowski

The head-up tilt table test (HUTT) with the upright phase is used to help determine an imbalance of the sympathetic nervous system that is related to abnormal electrocardiographic repolarization in children with vasovagal syncope (VVS) and also in patients with the long QT syndrome (LQTS). The study attempted to evaluate T wave morphology and QT and TpTe (Tpeak–Tend) intervals recorded in ECG during the HUTT for a more accurate diagnosis of children with VVS. The group investigated 70 children with a negative HUTT result: 40 patients with VVS and 30 healthy volunteers without syncope. The RR interval as well as TpTe, and QTc intervals were measured in lead V5 of electrocardiogram (ECG) on admission to the hospital and during three phases of the HUTT. In syncopal children, which included 23 children with bifid or flat T waves and 17 patients with normal T waves in the upright phase, the QTc and TpTe were longer (p < 0.001) compared to the other test phases and longer (p < 0.001) than in the control group, respectively, with the risk of arrhythmias. Only in the control group, the TpTe was shorter (p < 0.001) in the upright phase than in the other tilt phases. The TpTe in the upright phase (>70 ms) was a good discriminator, and was better than the QTc (>427 ms). Prolongation of electrocardiographic TpTe and QT intervals, in addition to the (abnormal T wave morphology recorded during the HUTT, are helpful for identifying VVS children more predisposed to ventricular arrhythmias with a latent risk of LQTS. Further studies are required to assess the value of these repolarization parameters in clinical practice.


Heart Rhythm ◽  
2004 ◽  
Vol 1 (3) ◽  
pp. 285-292 ◽  
Author(s):  
Jørgen K. Kanters ◽  
Søren Fanoe ◽  
Lars A. Larsen ◽  
Poul Erik Bloch Thomsen ◽  
Egon Toft ◽  
...  

Author(s):  
J.J. Struijk ◽  
J.K. Kanters ◽  
M.P. Andersen ◽  
T. Hardahl ◽  
C. Graff ◽  
...  

1999 ◽  
Vol 67 (2) ◽  
pp. 946-953 ◽  
Author(s):  
Paul J. Giannasca ◽  
Karen T. Giannasca ◽  
Alan M. Leichtner ◽  
Marian R. Neutra

ABSTRACT The biochemical features that distinguish human M cells from other intestinal epithelial cell types are important for understanding microbial pathogenesis and for targeting vaccines to the mucosal immune system. We applied a large panel of carbohydrate-specific monoclonal antibodies and lectins to Peyer’s patch and cecum biopsy specimens from three normal individuals and a patient with inflammatory bowel disease. The results show that human M-cell glycosylation patterns are distinct from those of other species examined and that human M cells preferentially display the sialyl Lewis A antigen. This carbohydrate epitope is also present in a small subpopulation of enterocytes in the follicle-associated epithelium and in goblet cell mucins.


1996 ◽  
Vol 44 (9) ◽  
pp. 1033-1042 ◽  
Author(s):  
A Gebert

The tonsil crypt epithelium contains membranous (M)-cells that transport antigens from the lumen to underlying lymphoid cells, thereby initiating specific immune responses. Mechanisms mediating the adhesion of antigens to the M-cell surface are important for effective and selective uptake of potential pathogens but are still poorly understood. Therefore, the carbohydrates present on crypt epithelial cells of the rabbit palatine tonsil were studied by lectin histochemistry. Ultrathin LR White sections were incubated with a panel of eight lectins conjugated to colloidal gold or biotin. The glycocalyx of the apical membrane of M-cells was selectively labeled by UEA-I, LTA, HPA, and VVA, whereas that of the remaining squamous epithelial cells preferentially bound RCA-I and PNA. WGA and ConA showed only little binding, with no discernible preference for any of the cell types. Double labeling of UEA-1 together with anti-vimentin antibodies revealed that UEA-I-positive epithelial cells also contained the rabbit M-cell marker vimentin, and vice versa. The results show that a specific composition of glycoconjugates, which differs from that on squamous epithelial cells, is found on M-cells of the rabbit tonsil. The M-cell-specific glycoproteins and glycolipids could be selectively targeted by microorganisms that adhere to M-cells and enter the host along this pathway.


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