The role of cardiac autonomic innervation in cardiomyopathy-related arrhythmias

Abstract

The cardiac autonomic nervous system consists of sympathetic and parasympathetic branches and is essential in maintaining cardiac homeostasis. For sympathetic innervation preganglionic sympathetic axons synapse with sympathetic neurons in the sympathetic chain, after which postganglionic fibers directly innervate either the myocardium or first synapse on the intrinsic cardiac ganglia. The aim of this thesis was to advance our current understanding regarding the role of innervation in the predisposition to ventricular arrhythmias and the development of ventricular arrhythmias in ischemic and nonischemic cardiomyopathy.

In this thesis, the controversy on which extracardiac ganglia contribute to cardiac autonomic innervation was explored. The existing quantification methods for cardiac innervation were evaluated and a novel tool for histological quantification of cardiac innervation was introduced. This method was then validated in transmural biopsy sections in the chronic phase of myocardial infarction in order to identify biopsies that may contribute to late arrhythmogenicity. Furthermore, sympathetic innervation was investigated in clinical patients with nonischemic cardiomyopathy and ventricular arrhythmias using 123I-MIBG SPECT. Changes in innervation patterns seemed to play an important role in arrhythmogenesis, both in ischemic as well as in nonischemic cardiomyopathy. The work highlighted in this thesis will form the base for future studies on this topic.