Localization of the Sites of Conduction Abnormalities in a Mouse Model of Myotonic Dystrophy

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Abstract
Heart Block in a Mouse Model of Myotonic Dystrophy. Introduction: 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. Methods and 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 bad 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 I 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. Conclusion: 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.