A Validated Smartphone-based Electrocardiogram Reveals Severe Bradyarrhythmias during Immobilizing Restraint in Mice of Both Sexes and Four Strains

Mouse handling and restraint affect behavior, physiology, and animal welfare, yet little information is available on how various mouse restraint methods affect cardiovascular parameters. We validated the use of a smartphone-based ECG sys- tem in mice by performing simultaneous smartphone and telemetry ECG recordings in conscious, restrained mice and in anesthetized mice. We observed that mice held in standard immobilizing restraint ("scruffing") experienced severe bradycardia. Mice of both sexes and 4 different strains (BALB/cJ, C57BL/6J, DBA/2J, and FVB/nJ) were restrained by 3 handlers using 3 different restraint methods: light restraint; 3-finger restraint, which creates a dorsal transverse fold of skin; and the standard immobilizing restraint, which creates a dorsal longitudinal fold of skin that results in a crease on the ventral neck. Regardless of the handler, immobilizing restraint, but not 3-finger restraint, produced severe bradycardia with irregular rhythm in all 4 strains and both sexes, with an average decrease in heart rate of 31%, or 211 bpm, and a maximal decrease of 79%, or 542 bpm. When evaluated using telemetry, immobilizing restraint produced severe arrhythmias such as junctional and ventricular escape rhythms, and second- and third-degree atrioventricular block. Sinus pauses were observed for an average of 4 min, but up to 6.8 min after release from immobilizing restraint. Atropine administration to C57BL/6J mice attenuated immobilizing restraint-induced bradycardia, supporting the hypothesis that pressure on cervical baroreceptors during stretching of the neck skin results in a vagally-mediated reflex bradycardia. Because of these profound cardiovascular effects, we recommend using the light or 3-finger restraint and avoiding or minimizing the use of immobilization restraint while handling mice.

The pathophysiology of vasovagal syncope

Vasovagal syncope, known also as neurogenic or neurocardiogenic syncope, accounts for about 30-40% of syncopes of unclear origin and is the most common type of syncope among children and adolescents. Vasovagal syncope is defined as a state of temporary loss of consciousness with reduction of muscle tone followed by sudden, rapid and total return of consciousness. Vasovagal syncope is caused by a drop in blood pressure and/or reflex bradycardia which occurs as a result of emotional or orthostatic stress. Consequently, in understanding the mechanism of neurogenic syncope, most attention is paid to the dysregulation of sympathetic-parasympathetic autonomic nervous system. The main objective of this study was to systematically review the pathomechanisms triggering a vasovagal reaction. The analysis is based on a review of the literature on this topic. Material was obtained using the library system ALEPH. The literature was obtained from databases such as PubMed, Medline and GBL. This study focused on the role of tilt testing in the diagnosis of vasovagal syncope as well as other tests used to assess the functioning of the autonomous control of the cardiovascular system in syncope.