Details

Autor(en) / Beteiligte

• Jungen, Christiane
• Scherschel, Katharina
• Flenner, Frederik
• Jee, Haesung
• Rajendran, Pradeep
• De Jong, Kirstie A
• Nikolaev, Viacheslav
• Meyer, Christian
• Ardell, Jeffrey L
• Tompkins, John D

Titel

Increased arrhythmia susceptibility in type 2 diabetic mice related to dysregulation of ventricular sympathetic innervation

Ist Teil von

• American journal of physiology. Heart and circulatory physiology, 2019-12, Vol.317 (6), p.H1328-H1341

Ort / Verlag

United States: American Physiological Society

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Patients with type 2 diabetes mellitus (T2DM) have a greater risk of developing life-threatening cardiac arrhythmias. Because the underlying mechanisms and potential influence of diabetic autonomic neuropathy are not well understood, we aimed to assess the relevance of a dysregulation in cardiac autonomic tone. Ventricular arrhythmia susceptibility was increased in Langendorff-perfused hearts isolated from mice with T2DM ( ). Membrane properties and synaptic transmission were similar at cardiac postganglionic parasympathetic neurons from diabetic and control mice; however, a greater asynchronous neurotransmitter release was present at sympathetic postganglionic neurons from the stellate ganglia of mice. Western blot analysis showed a reduction of tyrosine hydroxylase (TH) from the ventricles of mice, which was confirmed with confocal imaging as a heterogeneous loss of TH-immunoreactivity from the left ventricular wall but not the apex. In vivo stimulation of cardiac parasympathetic (vagus) or cardiac sympathetic (stellate ganglion) nerves induced similar changes in heart rate in control and mice, and the kinetics of pacing-induced Ca transients (recorded from isolated cardiomyocytes) were similar in control and cells. Antagonism of cardiac muscarinic receptors did not affect the frequency or severity of arrhythmias in mice, but sympathetic blockade with propranolol completely inhibited arrhythmogenicity. Collectively, these findings suggest that the increased ventricular arrhythmia susceptibility of type 2 diabetic mouse hearts is due to dysregulation of the sympathetic ventricular control. Patients with type 2 diabetes mellitus have greater risk of suffering from sudden cardiac death. We found that the increased ventricular arrhythmia susceptibility in type 2 diabetic mouse hearts is due to cardiac sympathetic dysfunction. Sympathetic dysregulation is indicated by an increased asynchronous release at stellate ganglia, a heterogeneous loss of tyrosine hydroxylase from the ventricular wall but not apex, and inhibition of ventricular arrhythmias in mice after β-sympathetic blockade.