Localization of the sites of conduction abnormalities in a Mouse Model of Myotonic Dystrophy

Heart Block in a Mouse Model of Myotonic Dystrophy. Introduction: A mouse s train lacking functional myotonic dystrophy protein kinase (DMPK) has recen tly been developed. DMPK-/- mice exhibit muscular and conduction abnormalit ies consistent with the disease; however, the site of abnormal cardiac cond uction is unknown. Methods and Results: Nine homozygous DMPK-/- mice and seven age matched wil d-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) con duction. Effective refractory periods (ERP) and functional refractory perio ds 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 c ompared to WT controls. HV intervals were very significantly prolonged as w ell (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 E RP 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 prematur e atrial stimulation. Conclusion: In this mouse model of myotonic dystrophy, AV conduction abnorm alities were localized to the supra-Hisian and infra-Hisian conduction tiss ues, with a higher predilection to the latter, a finding similar to the hum an form of the disease.