title: Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice.
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.
authors.forename: Ewa
authors.initials: E
authors.lastname: Soltysinska
authors.forename: Tobias
authors.initials: T
authors.lastname: Speerschneider
authors.forename: Sine V
authors.initials: SV
authors.lastname: Winther
authors.forename: Morten B
authors.initials: MB
authors.lastname: Thomsen
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000000981:diagnostic imaging / Q000503:physiopathology*; D053840:Brugada Syndrome; D000075224:Cardiac Conduction System Disease; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006329:Heart Conduction System / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012849:Sinoatrial Node / Q000000981:diagnostic imaging / Q000503:physiopathology*; D014463:Ultrasonography
references.citation: Methods Mol Biol. 2012;933:47-57
references.pmid: 22893400
references.citation: PLoS One. 2013 Nov 08;8(11):e76534
references.pmid: 24250786
references.citation: J Physiol. 2013 Dec 1;591(23):5923-37
references.pmid: 24099801
references.citation: Exp Clin Endocrinol Diabetes. 2003 Jun;111(4):215-22
references.pmid: 12845560
references.citation: Circulation. 1981 Jan;63(1):54-64
references.pmid: 7438408
references.citation: Cardiovasc Res. 2006 Feb 15;69(3):716-25
references.pmid: 16376323
references.citation: J Auton Nerv Syst. 1998 Mar 3;69(1):21-30
references.pmid: 9672120
references.citation: Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2387-96
references.pmid: 17220191
references.citation: Circulation. 2003 Aug 12;108(6):754-9
references.pmid: 12885755
references.citation: Acta Physiol (Oxf). 2013 Dec;209(4):262-71
references.pmid: 24119104
references.citation: Diabetes Care. 2004 May;27(5):1047-53
references.pmid: 15111519
references.citation: Diabetes. 1976 Jan;25(1):6-10
references.pmid: 1245267
references.citation: J Am Soc Echocardiogr. 2003 Nov;16(11):1144-9
references.pmid: 14608285
references.citation: Pacing Clin Electrophysiol. 1990 Dec;13(12 Pt 2):2086-90
references.pmid: 1704598
references.citation: Auton Neurosci. 2013 Dec;179(1-2):142-7
references.pmid: 24075402
references.citation: Diabetes Care. 1979 Mar-Apr;2(2):120-6
references.pmid: 520114
references.citation: Cardiology. 2002;98(1-2):33-9
references.pmid: 12373045
references.citation: Exp Physiol. 2009 Jun;94(6):648-58
references.pmid: 19218356
references.citation: Circ Res. 2003 Aug 22;93(4):277-9
references.pmid: 12893740
references.citation: Science. 1966 Sep 2;153(3740):1127-8
references.pmid: 5918576
references.citation: Endocrinology. 2010 Nov;151(11):5218-25
references.pmid: 20844006
references.citation: Circulation. 1996 Mar 1;93(5):1043-65
references.pmid: 8598068
references.citation: JAMA. 2007 Aug 15;298(7):765-75
references.pmid: 17699010
references.citation: Acta Physiol (Oxf). 2010 Sep;200(1):11-22
references.pmid: 20175764
references.citation: Cardiovasc Diabetol. 2013 Jan 17;12:19
references.pmid: 23327647
references.citation: Diabetes Res Clin Pract. 2004 Apr;64(1):51-8
references.pmid: 15036827
references.citation: Circulation. 2001 Mar 27;103(12):1638-43
references.pmid: 11273990
references.citation: Exp Physiol. 2008 Jan;93(1):83-94
references.pmid: 17911354
references.citation: Circulation. 2003 Jan 28;107(3):448-54
references.pmid: 12551870
references.citation: Circulation. 2007 Jan 23;115(3):387-97
references.pmid: 17242296
references.citation: Am Fam Physician. 2003 Apr 15;67(8):1725-32
references.pmid: 12725451
references.citation: Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:6560-3
references.pmid: 22255842
references.citation: Auton Neurosci. 2011 Jul 5;162(1-2):24-31
references.pmid: 21334985
references.citation: Mol Cell Biochem. 2007 Jun;300(1-2):39-46
references.pmid: 17541508
references.citation: Hypertension. 2009 Feb;53(2):387-92
references.pmid: 19029483
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5972-7
references.pmid: 19276108
references.citation: Chest. 2005 Oct;128(4):2611-4
references.pmid: 16236932
references.citation: Intern Med. 1995 Dec;34(12):1174-7
references.pmid: 8929644
references.citation: Horm Metab Res Suppl. 1992;26:84-7
references.pmid: 1490698
references.citation: J Mol Cell Cardiol. 1980 Dec;12(12):1341-51
references.pmid: 7205953
references.citation: Eur J Pharmacol. 2002 Jan 25;435(2-3):269-76
references.pmid: 11821037
references.citation: Circulation. 2004 Sep 7;110(10):1269-75
references.pmid: 15313952
references.citation: Diabetes Nutr Metab. 2000 Dec;13(6):346-9
references.pmid: 11232760
references.citation: J Clin Invest. 2013 Mar;123(3):1262-74
references.pmid: 23426181
references.citation: Am J Physiol Endocrinol Metab. 2004 Mar;286(3):E449-55
references.pmid: 14600074
references.citation: Acta Diabetol Lat. 1977 Sep-Dec;14(5-6):229-34
references.pmid: 613687
references.citation: Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2106-18
references.pmid: 17122193
references.citation: J Am Coll Cardiol. 1997 Jul;30(1):171-9
references.pmid: 9207639
references.citation: Diabetologia. 2012 May;55(5):1283-90
references.pmid: 22286552
references.citation: Nature. 2013 Oct 17;502(7471):372-6
references.pmid: 24077098
references.citation: Anesthesiology. 1992 Oct;77(4):669-74
references.pmid: 1416163
references.citation: Am J Physiol Heart Circ Physiol. 2008 Oct;295(4):H1634-41
references.pmid: 18708447