Abstract
Interactions along the neuro-cardiac axis are being explored with regard to their involvement in cardiac diseases, including catecholaminergic polymorphic ventricular tachycardia, hypertension, atrial fibrillation, long QT syndrome and sudden death in epilepsy. Interrogation of the pathophysiology and pathogenesis of neuro-cardiac diseases in animal models present challenges resulting from species differences, phenotypic variation, developmental effects and limited availability of data relevant at both the tissue and cellular level. By contrast, tissue-engineered models containing cardiomyocytes and peripheral sympathetic and parasympathetic neurons afford characterization of cellular- and tissue-level behaviours while maintaining precise control over developmental conditions, cellular genotype and phenotype. Such approaches are uniquely suited to long-term, high-throughput characterization using optical recording techniques with the potential for increased translational benefit compared to more established techniques. Furthermore, tissue-engineered constructs provide an intermediary between whole animal/tissue experiments and in silico models. This paper reviews the advantages of tissue engineering methods of multiple cell types and optical imaging techniques for the characterization of neuro-cardiac diseases.
Highlights
Neuro-cardiac disease describes the pathophysiological interaction between the nervous system (NS) and cardiovascular system (CVS), with pathological activity in one system resulting in pathological behaviour in the other [1]
NS to CVS pathogenesis was confirmed in a rodent model by Larsen et al for hypertension phenotypes [6], while the potential for CVS to NS pathogenesis has been highlighted by the observation that premature ventricular contractions (PVCs) have the capacity to excite a population of neurons independent of cardiac pacing and haemodynamic forces [19]
The complex pathophysiology of neuro-cardiac diseases is dependent upon an array of secretory factors, cell surface characteristics, rhythmic behaviours, connectivity and communication across multiple cell types including cardiomyocytes and neurons
Summary
Neuro-cardiac disease describes the pathophysiological interaction between the nervous system (NS) and cardiovascular system (CVS), with pathological activity in one system resulting in pathological behaviour in the other [1]. NS to CVS pathogenesis was confirmed in a rodent model by Larsen et al for hypertension phenotypes [6], while the potential for CVS to NS pathogenesis has been highlighted by the observation that premature ventricular contractions (PVCs) have the capacity to excite a population of neurons independent of cardiac pacing and haemodynamic forces [19]. Both neurons and cardiomyocytes are excitatory cells expressing similar ion channels and rhythmic behaviours. To illustrate the importance of such methods, we will first discuss how common cellular mechanisms, such as Ca2+ or K+ regulation through transmembrane channels, can affect both neural and cardiac tissue in CPVT and LQTS, as examples of diseases that were initially considered solely cardiac
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