City Research Online

Abstract

Sudden cardiac death (SCD), mediated by ventricular arrhythmia (VA), is the most common cause of death. The autonomic nervous system (ANS) is important in VA. Little is known about ventricular innervation within the normal heart. There are no previous detailed immunohistochemical studies comparing the ventricles from normal and cardiomyopathy hearts. The aim is to characterise the normal heart and its ventricular innervation and to see whether there are differences in cardiomyopathies.

At St George’s, University of London, we have established a unique database with research consented phenotyped normal human hearts and SCD cases. Ventricular fat and collagen is stained using picrosirius red. Distribution of intrinsic ventricular innervation is determined with immunohistochemistry utilising the general marker PGP9.5, tyrosine hydroxylase, sympathetic marker and the choline transporter, parasympathetic marker. Slide scanning, automated and blinded quantification with whole slide digital image analysis is used for collagen, fat, myocytes and innervation analysis.

Sudden arrhythmic death syndrome and cardiomyopathy cause a majority of non- ischaemic SCD. Gender is the most important predictor of heart weight. We provide a predicted heart weight equation and a reference table. Females have smaller atria, ventricles and valves but more subepicardial fat than males. The normal heart shows a greater innervation in the right ventricular outflow tract (RVOT). Dilated cardiomyopathy shows reduced myocytes. Cardiomyopathies show a trend towards general denervation. Cardiomyopathies demonstrate regional structural denervation in sections showing fibrosis.

Gender differences in cardiac structure should be considered when assessing for pathology. Innervation findings may aid in understanding why VA develops frequently in the RVOT. Denervation may occur as a patchy process with loss of nerve bundles in combination with fibrosis. Within DCM, the loss of myocytes and innervation may explain reduction of ventricular function. Further work is needed to establish the role of structural denervation in arrhythmogenesis.

Publication Type:	Thesis (Doctoral)
Subjects:	R Medicine R Medicine > RB Pathology R Medicine > RC Internal medicine
Departments:	School of Health & Medical Sciences > Cardiovascular and Genomics Research Institute School of Health & Medical Sciences > School of Health & Medical Sciences Doctoral Theses Doctoral Theses

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