Apoptosis in Myocytes in End-Stage Heart Failure

TLDR

Heart failure arises from diverse etiologies such as ischemic, hypertensive, toxic, and inflammatory disease. The study examined apoptosis in seven explanted hearts from patients with end‑stage heart failure to clarify the cellular mechanisms underlying myocardial deterioration. The authors analyzed four idiopathic dilated cardiomyopathy and three ischemic hearts, using in situ end‑labeling and agarose‑gel electrophoresis to detect DNA fragmentation as an apoptosis marker. Apoptosis was found in all idiopathic dilated cardiomyopathy hearts and one ischemic heart, with DNA laddering present only in dilated cardiomyopathy samples, indicating that myocyte loss via apoptosis contributes to progressive dysfunction in end‑stage cardiomyopathy.

Abstract

Heart failure can result from a variety of causes, including ischemic, hypertensive, toxic, and inflammatory heart disease. However, the cellular mechanisms responsible for the progressive deterioration of myocardial function observed in heart failure remain unclear and may result from apoptosis (programmed cell death).We examined seven explanted hearts obtained during cardiac transplantation for evidence of apoptosis. All seven patients had severe chronic heart failure: four had idiopathic dilated cardiomyopathy, and three had ischemic cardiomyopathy. DNA fragmentation (an indicator of apoptosis) was identified histochemically by in situ end-labeling as well as by agarose-gel electrophoresis of end-labeled DNA. Myocardial tissues obtained from four patients who had had a myocardial infarction one to two days previously were used as positive controls, and heart tissues obtained from four persons who died in motor vehicle accidents were used as negative controls for the end-labeling studies.Hearts from all four patients with idiopathic dilated cardiomyopathy and from one of the three patients with ischemic cardiomyopathy had histochemical evidence of DNA fragmentation. All four myocardial samples from patients with dilated cardiomyopathy also demonstrated DNA laddering, a characteristic of apoptosis, whereas this was not seen in any of the samples from patients with ischemic cardiomyopathy. Histological evidence of apoptosis was also observed in the central necrotic zone of acute myocardial infarcts, but not in myocardium remote from the infarcted zone. Rare isolated apoptotic myocytes were seen in the myocardium from the four persons who died in motor vehicle accidents.Loss of myocytes due to apoptosis occurs in patients with end-stage cardiomyopathy and may contribute to progressive myocardial dysfunction.