OBJECTIVES: The aim of this study was to evaluate the links between connexin43 (Cx43) expression, myocardial conduction velocity, and ventricular tachycardia in a model of healed myocardial infarction. BACKGROUND: Post-infarction ventricular arrhythmias frequently cause sudden death. Impaired myocardial conduction has previously been linked to ventricular arrhythmias. Altered connexin expression is a potential source of conduction slowing identified in healed scar border tissues. The functional effect of increasing border-zone Cx43 has not been previously evaluated. METHODS: Twenty-five Yorkshire pigs underwent anterior infarction by transient left anterior descending coronary artery occlusion, followed by weekly testing for arrhythmia inducibility. Twenty animals with reproducibly inducible sustained monomorphic ventricular tachycardia were randomized 2:1:1 to receive AdCx43, Adβgal, or no gene transfer. One week later, animals underwent follow-up electrophysiologic study and tissue assessment for several functional and molecular measures. RESULTS: Animals receiving AdCx43 had less electrogram fractionation and faster conduction velocity in the anterior-septal border zone. Only 40% of AdCx43 animals remained inducible for ventricular tachycardia, while 100% of controls were inducible after gene transfer. AdCx43 animals had 2-fold higher Cx43 protein levels in the anterior-septal infarct border, with similar percents of phosphorylated and intercalated disk-localized Cx43 compared with controls. CONCLUSIONS: These data mechanistically link Cx43 expression to slow conduction and arrhythmia susceptibility in the healed scar border zone. Targeted manipulation of Cx43 levels improved conduction velocity and reduced ventricular tachycardia susceptibility. Cx43 gene transfer represents a novel treatment strategy for post-infarction arrhythmias.
OBJECTIVES: The aim of this study was to evaluate the links between connexin43 (Cx43) expression, myocardial conduction velocity, and ventricular tachycardia in a model of healed myocardial infarction. BACKGROUND: Post-infarction ventricular arrhythmias frequently cause sudden death. Impaired myocardial conduction has previously been linked to ventricular arrhythmias. Altered connexin expression is a potential source of conduction slowing identified in healed scar border tissues. The functional effect of increasing border-zone Cx43 has not been previously evaluated. METHODS: Twenty-five Yorkshire pigs underwent anterior infarction by transient left anterior descending coronary artery occlusion, followed by weekly testing for arrhythmia inducibility. Twenty animals with reproducibly inducible sustained monomorphic ventricular tachycardia were randomized 2:1:1 to receive AdCx43, Adβgal, or no gene transfer. One week later, animals underwent follow-up electrophysiologic study and tissue assessment for several functional and molecular measures. RESULTS: Animals receiving AdCx43 had less electrogram fractionation and faster conduction velocity in the anterior-septal border zone. Only 40% of AdCx43 animals remained inducible for ventricular tachycardia, while 100% of controls were inducible after gene transfer. AdCx43 animals had 2-fold higher Cx43 protein levels in the anterior-septal infarct border, with similar percents of phosphorylated and intercalated disk-localized Cx43 compared with controls. CONCLUSIONS: These data mechanistically link Cx43 expression to slow conduction and arrhythmia susceptibility in the healed scar border zone. Targeted manipulation of Cx43 levels improved conduction velocity and reduced ventricular tachycardia susceptibility. Cx43 gene transfer represents a novel treatment strategy for post-infarction arrhythmias.
Authors: Jian-An Yao; Wajid Hussain; Pravina Patel; Nicholas S Peters; Penelope A Boyden; Andrew L Wit Journal: Circ Res Date: 2003-01-30 Impact factor: 17.367
Authors: J M de Bakker; R Coronel; S Tasseron; A A Wilde; T Opthof; M J Janse; F J van Capelle; A E Becker; G Jambroes Journal: J Am Coll Cardiol Date: 1990-06 Impact factor: 24.094
Authors: Martin Mollenhauer; Kai Friedrichs; Max Lange; Jan Gesenberg; Lisa Remane; Christina Kerkenpaß; Jenny Krause; Johanna Schneider; Thorben Ravekes; Martina Maass; Marcel Halbach; Gabriel Peinkofer; Tomo Saric; Dennis Mehrkens; Matti Adam; Florian G Deuschl; Denise Lau; Birgit Geertz; Kashish Manchanda; Thomas Eschenhagen; Lukas Kubala; Tanja K Rudolph; Yuping Wu; W H Wilson Tang; Stanley L Hazen; Stephan Baldus; Anna Klinke; Volker Rudolph Journal: Circ Res Date: 2017-04-12 Impact factor: 17.367
Authors: Anthony N DeMaria; Jeroen J Bax; Gregory K Feld; Barry H Greenberg; Jennifer L Hall; Mark A Hlatky; Wilbur Y W Lew; João A C Lima; Ehtisham Mahmud; Alan S Maisel; Sanjiv M Narayan; Steven E Nissen; David J Sahn; Sotirios Tsimikas Journal: J Am Coll Cardiol Date: 2013-01-22 Impact factor: 24.094
Authors: Cody A Rutledge; Fu Siong Ng; Matthew S Sulkin; Ian D Greener; Artem M Sergeyenko; Hong Liu; Joanna Gemel; Eric C Beyer; Ali A Sovari; Igor R Efimov; Samuel C Dudley Journal: J Am Coll Cardiol Date: 2014-01-08 Impact factor: 24.094