Mechanisms of Postinfarction Electrophysiological Abnormality: Sympathetic Neural Remodeling, Electrical Remodeling and Gap Junction Remodeling

Abstract

Of various functional impairments of electrical events in the heart, ventricular arrhythmias underlie the majority of deaths in patients with left ventricular dysfunction and heart failure after myocardial ischemia and infarction. As heart failure develops, pathophysiological remodeling of cardiac function occurs at multiple levels, spanning the spectrum from molecular and subcellular changes to those occurring at the organ system levels (Jin et al., 2008). Although advances in anti-arrhythmic agents and implantation of direct-current defibrillator have resulted in improved prevention of death due to arrhythmia in myocardial infarction, morbidity and mortality due to arrhythmias are still high in all over the world. In addition, in patients with severe congestive heart failure, ventricular arrhythmia is also a critical determinant of prognosis, because conservative anti-arrhythmia therapies are not very effective. Therapeutic strategies for arrhythmias have been focused mainly on electrophysiological aspects with little consideration of structural or cellular bases for arrhythmogenesis. Thus, the exact cellular mechanism underlying lethal arrhythmias is undetermined. Identification of arrhythmogenic substrates from viewpoints other than electrophysiological ones is essential (Takamatsu, 2008). Despite decades of investigation, the precise mechanisms that underlie the electrophysiological abnormality remain elusive. In this chapter we therefore focus on three main issues with an emphasis on the mechanisms responsible for these adaptations: sympathetic neural remodeling, electrical remodeling and gap junction remodeling.