Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation.

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.