Mouse models of arrhythmogenic cardiovascular disease: challenges and opportunities

Abstract

Arrhythmogenic cardiovascular disease is associated with significant morbidity and mortality and, in spite of therapeutic advances, remains an enormous public health burden. The scope of this problem motivates efforts to delineate the molecular, cellular and systemic mechanisms underlying increased arrhythmia risk in inherited and acquired cardiac and systemic disease. The mouse is used increasingly in these efforts owing to the ease with which genetic strategies can be exploited and mechanisms can be probed. The question then arises whether the mouse has proven to be a useful model system to delineate arrhythmogenic cardiovascular disease mechanisms. Rather than trying to provide a definite answer, the goal here is to consider the issues that arise when using mouse models and to highlight the opportunities.

Transverse cardiac slicing and optical imaging for analysis of transmural gradients in membrane potential and Ca2+ transients in murine heart

“…). Within the cardiovascular research community, the mouse has been widely used for exploring molecular, cellular and systemic mechanisms underlying inherited and acquired ventricular arrhythmic diseases (Nerbonne, ). As transgenic technology has advanced, mutagenesis has become much easier to carry out in mice and an increasing number of genetically modified mouse systems have been generated for the study of cardiac arrhythmias (Sabir et al .…”

Non-invasive ECG recording and QT interval correction assessment in anesthetized rats and mice

“…Rats and mice are the most common species used in experimental cardiac physiology and electrophysiology studies (Zaragoza et al 2011, Nerbonne 2014, Surikow et al 2017. Several disease models including myocardial infarction (Heywood et al 2017), diabetic cardiomyopathy (Bugger & Abel 2009), hypertrophic and dilated cardiomyopathy (Xu et al 2014, Yu et al 2014), Chagas' disease (Roman-Campos et al 2013) and QT syndrome (Drum et al 2014) are well established in such animals.…”

Limulus and heart rhythm

“…A critical function of the cor heart—pumping blood—is enabled by the sequential and recurrent contraction (systole) and relaxation (diastole) of its myocardium (Kobayashi & Irisawa, ). The heart, with each of its compartment/chamber, myocardial layer, and constitutive cells, possesses unique properties (Nerbonne, ). Within the heart, either muscle fibers or single cells trigger action potentials (AP) that mimic properties of the whole compartment/chamber (Barbic, Moreno, Harris, & Kay, ).…”

“…Because the late repolarization phase does not start timely, the MP starts to oscillate, triggers recurrent EADs, and remains at pseudoplateau (Figure b). Responsible K + ion channels are of distinct types during the two phases in mammals (Nerbonne, ). EADs similar to spikes of neurons (Kodirov, ; Kodirov, Wehrmeister, & Colom, ) exhibit both amplitude and frequency adaptations (Figure c,d).…”