Cardiac electrophysiology: purpose tailored animal models for complex conditions

This commentary refers to ‘Animals in cardiovascular research: important role of rabbit models in cardiac electrophysiology’, by K.E. Odening et al., 2020;41:2036. We thank the authors for their interest in our article on the use of animals in cardiovascular research1,2 and greatly appreciate their input on rabbits as a highly relevant and representative model for studies in cardiac electrophysiology. Indeed, due to the focus on small, genetically modified, and large animal models, this species was underrepresented in our work. Odening et al.,1 correctly emphasize on the undeniable fact that cardiac electrophysiology in rabbits closely resembles that one of humans and therefore this species has been extensively used in academic research and pharmaceutical safety screening.3 Beside dogs, rabbits are quite susceptible for developing spontaneous arrhythmia (including high incidence of torsade des points) in models of atrio-ventricular block and in hypertrophy/heart failure (HF) models induced by volume and/or pressure overload.3,4 Furthermore, long established and validated preparations of Langendorff perfused and ex vivo working rabbit hearts (from either healthy or animals with experimentally induced cardiac conditions such as HF) provide scientists with (electro-) physiological data (i.e. spatiotemporal pattern of action potential alternations) which are otherwise almost impossible to obtain. On the other hand, arrhythmia models using myocardial infarction as the substrate for re-entry might be challenging in rabbits due to the variability in coronary anatomy and in particular, the short, relatively small and early branching left anterior descending (LAD) coronary artery. Hence, protocol adaptations such as occlusion of the marginal branch of left circumflex artery (LCX) may need to be considered.5 Beside rabbits, rodents can provide deep insights into molecular [e.g. γ2 adenosine monophosphate-activated protein kinase (AMPK)-related bradycardia] processes related to spontaneous arrhythmias. Nevertheless, they may better represent specific pathological mechanisms rather than more common and complex conditions. For other type of studies (i.e. resuscitation strategies or device-based therapies), the use of large animals is often more preferred. However due to the plethora of disease aspects, it’s complexity and species-, and even model-specific differences, the decision on ideal translational model may often be challenging and should therefore be made on a case-by-case basis and in a tailored fashion. Last but not least, and building on the comprehensive comment from Odening et al., we would like to point the increasingly important role of genetically engineered models. In the era of increased social scrutiny and financial pressure, emergence of novel (e.g. humanized, knock-in, and conditional mutations) rabbit, rodent, and non-mammalian models should be expected, not only in the field of electrocardiophysiology but also in the broader arena of cardiovascular research.6 Conflict of interest: none declared.