Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice.

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  • Author(s): Soltysinska E; Speerschneider T; Winther SV; Thomsen MB
  • Source:
    Cardiovascular diabetology [Cardiovasc Diabetol] 2014 Aug 12; Vol. 13, pp. 122. Date of Electronic Publication: 2014 Aug 12.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101147637 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2840 (Electronic) Linking ISSN: 14752840 NLM ISO Abbreviation: Cardiovasc Diabetol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2002-
    • Subject Terms:
      Arrhythmias, Cardiac/*physiopathology ; Diabetes Mellitus, Experimental/*physiopathology ; Heart Conduction System/*abnormalities ; Sinoatrial Node/*physiopathology; Animals ; Arrhythmias, Cardiac/diagnostic imaging ; Brugada Syndrome ; Cardiac Conduction System Disease ; Diabetes Mellitus, Experimental/diagnostic imaging ; Heart Conduction System/diagnostic imaging ; Heart Conduction System/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Sinoatrial Node/diagnostic imaging ; Ultrasonography
    • Abstract:
      Background: The aim of this study was to probe cardiac complications, including heart-rate control, in a mouse model of type-2 diabetes. Heart-rate development in diabetic patients is not straight forward: In general, patients with diabetes have faster heart rates compared to non-diabetic individuals, yet diabetic patients are frequently found among patients treated for slow heart rates. Hence, we hypothesized that sinoatrial node (SAN) dysfunction could contribute to our understanding of the mechanism behind this conundrum and the consequences thereof.
      Methods: Cardiac hemodynamic and electrophysiological characteristics were investigated in diabetic db/db and control db/+ mice.
      Results: We found improved contractile function and impaired filling dynamics of the heart in db/db mice, relative to db/+ controls. Electrophysiologically, we observed comparable heart rates in the two mouse groups, but SAN recovery time was prolonged in diabetic mice. Adrenoreceptor stimulation increased heart rate in all mice and elicited cardiac arrhythmias in db/db mice only. The arrhythmias emanated from the SAN and were characterized by large RR fluctuations. Moreover, nerve density was reduced in the SAN region.
      Conclusions: Enhanced systolic function and reduced diastolic function indicates early ventricular remodeling in obese and diabetic mice. They have SAN dysfunction, and adrenoreceptor stimulation triggers cardiac arrhythmia originating in the SAN. Thus, dysfunction of the intrinsic cardiac pacemaker and remodeling of the autonomic nervous system may conspire to increase cardiac mortality in diabetic patients.
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    • Publication Date:
      Date Created: 20140813 Date Completed: 20150330 Latest Revision: 20231104
    • Publication Date:
      20231215
    • Accession Number:
      PMC4149194
    • Accession Number:
      10.1186/s12933-014-0122-y
    • Accession Number:
      25113792