Guidelines for assessment of cardiac electrophysiology and arrhythmias in small animals

Abstract

Cardiac arrhythmias are a major cause of morbidity and mortality worldwide. Although recent advances in cell-based models, including human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM), are contributing to our understanding of electrophysiology and arrhythmia mechanisms, pre-clinical animal studies of cardiovascular disease remain a mainstay. Over the past several decades, animal models of cardiovascular disease have advanced our understanding of pathological remodeling, arrhythmia mechanisms, drug effects, and have led to major improvements in pacing and defibrillation therapies. There exist a variety of methodological approaches for assessment of cardiac electrophysiology, and a plethora of parameters may be assessed with each approach. This Guidelines article will provide an overview of the strengths and limitations of several common techniques used to assess electrophysiology and arrhythmia mechanisms at the whole animal, whole heart, and tissue level, with a focus on small animal models. We also define key electrophysiological parameters that should be assessed, along with their physiological underpinnings, and the best methods with which to assess these parameters.

Natriuretic Peptide Receptor B Protects Against Atrial Fibrillation by Controlling Atrial cAMP Via Phosphodiesterase 2

“…Consistent with this, it is known that enhanced SNS activity can contribute to AF initiation and maintenance 6,9 and mice normally have relatively high SNS activity in vivo. 38,39 Furthermore, patients with persistent AF have increased cardiac sympathetic nerve density and increased circulating catecholamine levels. 7 Large animal models also demonstrate SNS remodeling leading to AF.…”

A Minimally Invasive Approach for Cardiac Electrophysiology Studies in Mice

“…Arrhythmia susceptibility was assessed using the above S1-S2 decremental pacing protocol and a fast S1-S1 burst pacing (cycle length: 50 ms, 40 ms and 30 ms, respectively). Each S1-S1 pacing train lasted for 20 s. The recovery interval was at least 30 s between pacing trains [20]. AF was defined if more than 0.5 s of continuous high frequency and polymorphic P waves appeared after termination of pacing.…”

Adapting to a new environment: postnatal maturation of the human cardiomyocyte

“…75 beats min −1 ) humans Bratincsák et al, 2020;Jann Hau, 2010;Janssen & Periasamy, 2007;Rudolph, 2009). These physiological differences are supported by both anatomical adaptations and underlying molecular mechanisms (Edwards & Louch, 2017;Milani-Nejad & Janssen, 2014;Odening et al, 2021;Ripplinger et al, 2022). (1970) To bridge this gap, hPSC-CM have gained prominence because these cells have structural features and a gene/protein expression profile that is similar to primary human cardiomyocytes (Casini et al, 2017;Denning et al, 2016;Liang et al, 2013).…”

“…75 beats min −1 ) humans Bratincsák et al., 2020; Jann Hau, 2010; Janssen & Periasamy, 2007; Rudolph, 2009). These physiological differences are supported by both anatomical adaptations and underlying molecular mechanisms (Edwards & Louch, 2017; Milani‐Nejad & Janssen, 2014; Odening et al., 2021; Ripplinger et al., 2022).…”