title: Localization of the sites of conduction abnormalities in a mouse model of myotonic dystrophy.
abstract: BACKGROUND
  A mouse strain lacking functional myotonic dystrophy protein kinase (DMPK) has recently been developed. DMPK-/- mice exhibit muscular and conduction abnormalities consistent with the disease; however, the site of abnormal cardiac conduction is unknown.
  
  
  RESULTS
  Nine homozygous DMPK-/- mice and seven age matched wild-type (WT) controls underwent in vivo electrophysiologic studies using an endocardial 2-French catheter. Baseline intervals as well as Wenckebach and 2:1 cycle lengths were measured to assess AV and ventriculoatrial (VA) conduction. Effective refractory periods (ERP) and functional refractory periods were determined during atrial and ventricular premature stimulation. His-bundle recordings were obtained on all the studied animals (16/16). DMPK-/- mice had significantly prolonged PR (48.1 +/- 5.5 vs 40.9 +/- 3.9 msec, P = 0.010) and AH (36.7 +/- 4.0 vs 31.6 +/- 4.8 msec, P = 0.037) intervals compared to WT controls. HV intervals were very significantly prolonged as well (14.7 +/- 2.0 vs 10.3 +/- 0.8 msec; P < 0.0001). Three of 9 DMPK-/- and 1 of 7 WT mice exhibited VA block. Atrial ERP was reached before AV node ERP in 2 (22%) of 9 of the knockout mice and 5 (71%) of 7 of the controls (P = 0.06). Only one mouse (DMPK-/-) exhibited infra-Hisian block on premature atrial stimulation.
  
  
  CONCLUSIONS
  In this mouse model of myotonic dystrophy, AV conduction abnormalities were localized to the supra-Hisian and infra-Hisian conduction tissues, with a higher predilection to the latter, a finding similar to the human form of the disease.
authors.affiliation: Division of Cardiology, Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts, USA.
authors.forename: S
authors.initials: S
authors.lastname: Saba
authors.forename: B A
authors.initials: BA
authors.lastname: Vanderbrink
authors.forename: B
authors.initials: B
authors.lastname: Luciano
authors.forename: M J
authors.initials: MJ
authors.lastname: Aronovitz
authors.forename: C I
authors.initials: CI
authors.lastname: Berul
authors.forename: S
authors.initials: S
authors.lastname: Reddy
authors.forename: D
authors.initials: D
authors.lastname: Housman
authors.forename: M E
authors.initials: ME
authors.lastname: Mendelsohn
authors.forename: N A
authors.initials: NA
authors.lastname: Estes
authors.forename: P J
authors.initials: PJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D004562:Electrocardiography; D006321:Heart / Q000503:physiopathology*; D006329:Heart Conduction System; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009223:Myotonic Dystrophy / Q000235:genetics / Q000503:physiopathology*; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000235:genetics
chemical_list: C585517:DMPK protein, human; C585516:DMPK protein, mouse; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases