3D anatomical modelling of the human cardiac conduction system

UoM administered thesis: Master of Philosophy

Abstract

Background. The cardiac conduction system is responsible for the initiation and propagation of action potentials in the heart. The sinus node is the primary pacemaker in the heart. Action potentials then pass through the atrial myocardium to the atrioventricular node, into the His bundle and finally the Purkinje fibre network. A detailed understanding of the anatomy of the cardiac conduction system is important in understanding its functioning and potential role in arrhythmogenesis. The creation of 3D models is an increasingly important field as they are powerful tools and have many potentially valuable educational, research and clinical uses such as teaching complex anatomy can and in computer modelling studies of disease.Aims. In this study the aim was to create 3D anatomical computer models of the human sinus node and complete paranodal area, and also create a reconstruction of the major components of the cardiac conduction system of the human heart from an intact heart.Methods. A formalin fixed human heart and a right atrial sample containing the intercaval region were CT scanned. The samples were then frozen and serially sectioned. Masson's trichrome histology and immunohistochemistry using antibodies against Cx43, HCN4 and KCa1.1 were used to identify the major components of the cardiac conduction system. Avizo software was used to segment structures and create 3D anatomical reconstructions. 3D measurements of structures made. Results. 1) A 3D anatomical reconstruction of the sinus node and paranodal was successfully created. The sinus node is a crescent shaped structure 1.6 cm in length. The paranodal area is ellipsoid in shape and 2 cm in length. The two structures are in close proximity but there were no connections found between them. 2) A 3D anatomical reconstruction of the human heart and major components of the cardiac conduction system was successfully created from tissue sections of the intact heart. The His bundle is the closest structure to the non-coronary cusp of the aortic valve. 3) KCa1.1 appears to be more highly expressed in the sinus node than atrial muscle at both the mRNA and protein level. Discussion. This study demonstrates that it is possible to create a 3D anatomical reconstruction of the human heart based on serial sections of the entire human heart. This 3D computer anatomical model has many potential clinical and educational uses. The model can be used in computer modelling studies into cardiac pacemaking and arrhythmia and particularly in relation to aortic valve replacement, this model may be useful in helping improve the design of the implants in order for them to have less of an impact on the cardiac conduction system. The KCa1.1 channel may be a potential target in the treatment of arrhythmia.

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Original languageEnglish
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Award date3 Jan 2015