Abstract
In cardiovascular research, several mouse strains with differing genetic backgrounds are used to investigate mechanisms leading to and sustaining ventricular arrhythmias. The genetic background has been shown to affect the studied phenotype in other research fields. Surprisingly little is known about potential strain-specific susceptibilities towards ventricular arrhythmias in vivo. Here, we hypothesized that inter-strain differences reported in the responsiveness of the β-adrenergic pathway, which is relevant for the development of arrhythmias, translate into a strain-specific vulnerability. To test this hypothesis, we characterized responses to β-adrenergic blockade (metoprolol) and β-adrenergic stimulation (isoproterenol) in 4 mouse strains commonly employed in cardiovascular research (Balb/c, BS, C57Bl/6 and FVB) using telemetric ECG recordings. We report pronounced differences in the electrical vulnerability following isoproterenol: Balb/c mice developed the highest number and the most complex arrhythmias while BS mice were protected. Balb/c mice, therefore, seem to be the background of choice for experiments requiring the occurrence of arrhythmias while BS mice may give insight into electrical stability. Arrhythmias did not correlate with the basal β-adrenergic tone, with the response to β-adrenergic stimulation or with the absolute heart rates during β-adrenergic stimulation. Thus, genetic factors dominate the susceptibility to ventricular arrhythmias in this model of β-adrenergic stimulation.
Highlights
In cardiovascular research, rodent models are commonly used to advance the understanding of mechanisms leading to and sustaining ventricular arrhythmias
We hypothesized that mouse strains with a high response to a β-adrenergic activation are more vulnerable to ventricular arrhythmias than those with a low β-adrenergic responsiveness
A plethora of mouse strains with differing genetic backgrounds are commercially available and used today
Summary
Rodent models are commonly used to advance the understanding of mechanisms leading to and sustaining ventricular arrhythmias. A high response to β-adrenergic activation has been linked to an increased risk for ventricular arrhythmias due to augmented Ca2+ loading of the sarcoplasmic reticulum and excessive activation of the Na+-Ca2+ exchanger[9,10,11,12] This suggests that inter-strain differences in β-adrenergic responsiveness may translate into substantial differences in the susceptibility to ventricular arrhythmias between different mouse strains. We hypothesized that mouse strains with a high response to a β-adrenergic activation are more vulnerable to ventricular arrhythmias than those with a low β-adrenergic responsiveness To test this hypothesis, we selected 4 mouse strains which are commonly used in cardiovascular research and which are reported to differ substantially in their responses to β-adrenergic blockade and activation[7,8,13]: Balb/c and FVB mice with contrasting adrenergic responsiveness, as well as Black Swiss (BS) and C57Bl/6 (C57Bl/6) mice with intermediate phenotypes. Contrasting our hypothesis, the electrical stability did not correlate with the β-adrenergic responsiveness of the animals
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
