Spontaneous and inducible ventricular arrhythmias after myocardial infarction in mice

Tetsuo Betsuyaku, Shigeto Kanno, Deborah L. Lerner, Richard B. Schuessler, Jeffrey E. Saffitz, Kathryn A. Yamada

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Introduction Remodeling of gap junctions has been implicated in development of ventricular arrhythmias following myocardial infarction (MI) but the specific contribution of reduced electrical coupling is not known. We addressed this question using hearts from mice heterozygous for a connexin43 null allele (Cx43+/-). Methods To determine whether Cx43-deficient mice exhibit increased spontaneous ventricular arrhythmias in the setting of chronic ischemic heart disease, radiofrequency transmitters were implanted in wild-type and Cx43+/- mice 2 days or 9 weeks after left anterior descending coronary artery ligation or sham operations. ECGs were recorded from unanesthetized, unrestrained mice 1 and 10 weeks after MI. Isolated, perfused hearts excised 1 and 10 weeks after MI were subjected to programmed electrical stimulation to induce arrhythmias. Results and conclusions Hearts with infarcts exhibited more spontaneous and inducible arrhythmias, but there was no significant difference between wild-type and Cx43-deficient mice. Fewer hearts exhibited spontaneous ventricular tachycardia (VT) in vivo than were inducible in vitro, suggesting that structural and functional substrates for inducible VT in isolated hearts may not be sufficient for initiation and maintenance of sustained VT in vivo. Previous studies have shown that Cx43-deficient mice exhibit more VT than wild-type mice during acute regional ischemia. Mice with MI exhibit increased arrhythmias. However, reduced coupling in Cx43-deficient mice does not significantly enhance spontaneous or inducible VT after MI.

Original languageEnglish
Pages (from-to)156-164
Number of pages9
JournalCardiovascular Pathology
Volume13
Issue number3
DOIs
StatePublished - May 1 2004

Keywords

  • Arrhythmia
  • Connexin43
  • Mice
  • Myocardial infarction
  • Ventricular tachycardia

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