Abstract
BackgroundThe 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.MethodsCardiac hemodynamic and electrophysiological characteristics were investigated in diabetic db/db and control db/+ mice.ResultsWe 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.ConclusionsEnhanced 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.
Highlights
The aim of this study was to probe cardiac complications, including heart-rate control, in a mouse model of type-2 diabetes
The incidence of cardiovascular disease is higher among diabetic patients [2], and they often die from cardiovascular complications [3]
A hypercontractile systolic function in db/db mice was indicated by a greater fractional shortening (Figure 1B) and larger ejection fraction (db/+: 67 ± 2 versus db/db: Table 1 Characteristics of the control and diabetic mice db/+ (n = 11) db/db (n = 9)
Summary
The aim of this study was to probe cardiac complications, including heart-rate control, in a mouse model of type-2 diabetes. Elevated resting heart rate is associated with an increased risk of cardiovascular complications and sudden cardiac death in the general population and in T2DM patients [4,5,6]. Reports of impaired atrio-ventricular node in diabetic patients [11,12] supports the clinical observation that the cardiac conduction system, especially the function of the nodes, are compromised in T2DM. There are strong clinical indications of altered sino-atrial node (SAN) function in T2DM and that this could contribute to the increased cardiovascular mortality in this large patient population
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