Cardiac electrophysiologic abnormalities in the CREBA133 transgenic mouse model of idiopathic dilated cardiomyopathy

Wei Zhu, John J. Lepore, Samir Saba, Saju Joseph, Mark S. Link, Munther K. Homoud, N. A.Mark Estes, Paul J. Wang, Jeffrey M. Leiden

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Introduction: We hypothesized that the transgenic mice expressing a dominant-negative form of the CREB transcription factor (CREBA133) under the control of the cardiac myocyte-specific α-MHC promoter and displaying dilated cardiomyopathy would exhibit electrophysiologic abnormalities similar to those observed in human cardiomyopathy. Methods and Results: Invasive electrophysiologic studies were performed on two age groups of mice: 11-week-old mice (n = 20, 9 transgenic mice and 11 wild-type controls) and 17-week-old mice (n = 16, 7 transgenic mice and 9 wild-type controls). Five additional transgenic mice underwent ambulatory ECG monitoring to determine the cause of death. The 11-week-old CREBA133 transgenic mice had longer PR and AH intervals than 11-week-old wild-type controls (P < 0.001), whereas at 17 weeks of age the transgenic mice also demonstrated increased HV intervals and widened QRS duration (P < 0.05). At both 11 weeks and 17 weeks of age, AV Wenckebach cycle length, 2:1 AV cycle length, and AV nodal functional and effective refractory periods were significantly longer in transgenic mice than in controls (P < 0.05). Although no ventricular arrhythmias were inducible at 11 weeks of age, at 17 weeks of age, ventricular tachycardia was induced in 4 of the 7 CREBA133 transgenic mice but in none of the 9 wild-type controls. All 5 CREBA133 transgenic mice that underwent ambulatory ECG monitoring revealed high-grade AV block, but not ventricular arrhythmia, at the time of death. Conclusion: These data suggest that CREBA133 transgenic mice manifest abnormalities of AV nodal and infra-Hisian conduction and inducibility of ventricular arrhythmia, which are characteristics of human dilated cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)982-989
Number of pages8
JournalJournal of Cardiovascular Electrophysiology
Volume14
Issue number9
DOIs
StatePublished - Sep 1 2003

Keywords

  • CREB transgenic mouse
  • Cardiac electrophysiology
  • Idiopathic dilated cardiomyopathy
  • Sudden death
  • Ventricular depolarization

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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