Heart block in mice overexpressing calcineurin but not NF-AT3.

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  • Additional Information
    • Source:
      Publisher: Oxford Journals Country of Publication: England NLM ID: 0077427 Publication Model: Print Cited Medium: Print ISSN: 0008-6363 (Print) Linking ISSN: 00086363 NLM ISO Abbreviation: Cardiovasc Res Subsets: MEDLINE
    • Publication Information:
      Publication: 2008- : Oxford : Oxford Journals
      Original Publication: London, British Medical Assn.
    • Subject Terms:
      Calcineurin/*genetics ; DNA-Binding Proteins/*genetics ; Heart Block/*metabolism ; Hypertrophy, Left Ventricular/*metabolism ; Nuclear Proteins/*genetics ; Transcription Factors/*genetics; Animals ; Calcineurin/metabolism ; Electrocardiography ; Gene Expression ; Heart Conduction System ; Hypertrophy, Left Ventricular/embryology ; Mice ; Mice, Transgenic ; NFATC Transcription Factors ; Perfusion
    • Abstract:
      Objective: Overexpression of calcineurin causes cardiac hypertrophy and arrhythmic deaths. During disease development, sinus bradycardia followed by high degree atrioventricular (AV) block finally culminating in ventricular asystole has been observed over time in calcineurin hearts. AV block is associated with the development of pleomorphic ventricular tachycardia in mice and downregulation of potassium currents in ventricular myocytes. We tested the hypothesis that the abnormalities of AV block and propensity to ventricular tachycardia relate to overexpression of calcineurin independent of the development of hypertrophy.
      Methods: Cardiac electrophysiologic properties were compared in isolated perfused hearts with ventricular hypertrophy due to overexpression of calcineurin or NF-AT3 and in their corresponding wild types at 15 or 30 days of age.
      Results: Compared to wild-type hearts, significant prolongation of sinus node recovery times was noted in both NF-AT3 and calcineurin hearts. Compared to wild-type hearts, Wenckebach cycle length (WCL) and the left ventricular effective refractory period (LVERP) were significantly prolonged in the calcineurin hearts (p<0.05) but not NF-AT3 hearts. In calcineurin mice, left ventricular effective refractory period impinged on Wenckebach cycle length resulting in a significant correlation between left ventricular effective refractory period and Wenckebach cycle length (r(2)=0.56). No such correlation was observed for wild type or NF-AT3 hearts. At 30 days of development, ventricular tachycardia developed in 70% of calcineurin hearts compared to 0% wild-type hearts (p=0.003), whereas ventricular tachycardia was observed in 33% of NF-AT3 hearts and 10% of corresponding wild-type hearts (p=NS).
      Conclusions: The prolonged ventricular refractoriness, seen only in calcineurin hearts, impinges on Wenckebach cycle length resulting in heart block and is associated with propensity to ventricular tachycardia.
    • Accession Number:
      0 (DNA-Binding Proteins)
      0 (NFATC Transcription Factors)
      0 (Nuclear Proteins)
      0 (Transcription Factors)
      EC 3.1.3.16 (Calcineurin)
    • Publication Date:
      Date Created: 20041113 Date Completed: 20050217 Latest Revision: 20081121
    • Publication Date:
      20221213
    • Accession Number:
      10.1016/j.cardiores.2004.08.005
    • Accession Number:
      15537502