Download 2016 department of medicine research day

2016 DEPARTMENT OF MEDICINE RESEARCH DAY
Title of Poster: Increased incidence of ventricular arrhythmias in type 2 diabetic mice
not due to loss of ganglionic neurotransmission at intrinsic cardiac ganglia
Presenter: John D. Tompkins, PhD
Division: Cardiology
☒ Faculty ☐ Fellow ☐ Resident ☐ Post-doc Research Fellow ☐ Graduate Student ☐ Medical Student ☐Other
Principal Investigator/Mentor: John D. Tompkins, PhD
Co-Investigators: Christiane Jungen, MD
Thematic Poster Category: Neurobiology, Smooth, Striated and Cardiac Muscle Function, Cardiac Conduction
Systems and Arrhythmias, Biology of Perception and Pain, Psychoneuroimmunology
Abstract
Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing life threatening
cardiac arrhythmias. An imbalanced regulation of cardiac physiology by the autonomic nervous
system is thought to be a contributing factor. Parasympathetic nerve activity is reduced in T2DM mice
and humans, and interruption of ganglionic neurotransmission at cardiac ganglia in the isolated mouse
heart is proarrhythmic. To determine if T2DM mice are susceptible to ventricular arrhythmias and if
interruption of ganglionic neurotransmission contributes to the phenotype, we evaluated the sensitivity
of diabetic hearts to pacing induced ventricular arrhythmias and assessed viability of intracardiac
parasympathetic nerves. Arrhythmia susceptibility was measured in retrogradely perfused hearts,
isolated from 12 week old diabetic (db/db) and control (db het) mice, using standard extrastimulus
pacing and burst stimulation protocols. Basic indices of cardiac electrophysiology (atrial refractory
period, AV nodal recovery time, Wenckebach point, ventricular refractory period) were similar between
groups. Ventricular tachycardia, however, was inducible in 7/7 (100%) T2DM mouse hearts versus
1/7 (14%) controls (p = 0.0014). In isoflurane anesthetized mice, unilateral stimulation of the vagus
nerve produced similar bradycardic responses in both diabetic and control mice. Intracellular
recordings from cardiac neurons in isolated cardiac ganglia showed no change in membrane properties
or synaptic transmission in control or T2DM mice. In conclusion, ex vivo hearts from obese T2DM
mice are susceptible to pacing induced ventricular arrhythmias and provide a useful model to study
arrhythmogenesis in the diabetic heart. The arrhythmia susceptibility does not result from a loss of
parasympathetic neurotransmission at cardiac ganglia or a reduction in SA node sensitivity to
acetylcholine, suggesting the loss of parasympathetic drive previously reported is centrally mediated.