Something old, something new: Changing views on the cellular mechanisms of heart failure

Abstract

See article by Fauconnier et al. [84] (pages 204–212) in this issue. Despite improvements in therapy, mortality in heart failure (HF) remains high, and there is a need for alternative and additional approaches [1,2]. The possibility of replacement and/or supporting the failing heart with new cardiomyocytes from stem cells, implanted or recruited locally, is one of the exciting possibilities under investigation [3]. Other approaches aim at improving the function of the failing myocytes. Although the temporal and causal relationship between the development of chronic HF and myocyte dysfunction remains unclear [4], there is little doubt that at the time of advanced HF, the isolated myocytes have reduced contractility, in particular under normal physiological stress, i.e. at physiological heart rates and in the response to adrenergic stimulation. The first trials with chronic inotropic therapy, however, had a very poor outcome, and the idea was abandoned for quite a long time [5]. However, new ideas to improve contractility of the myocytes are growing from recent insights into the cellular mechanisms underlying the contractile dysfunction and the link to signals for remodeling. In this editorial, we will briefly review the background of excitation–contraction coupling and changes in heart failure against which these views developed and discuss some future perspectives. The process of excitation–contraction coupling has been reviewed extensively and is schematically illustrated in Fig. 1 [6,7]. Central in the link between membrane depolarization and contraction is the transient elevation of [Ca2+]i, or [Ca2+]i transient. Fig. 1 Schematic of excitation–contraction coupling. During the action potential, Ca2+ enters the cell through voltage-activated Ca2+ channels, with a small additional amount entering through the Na/Ca exchanger, NCX, depending on the [Na+]i. This Ca2+ acts as trigger to activate the Ca … *Corresponding author. Tel.: +32 16 347153; fax: +32 16 345844. Email address: Karin.Sipido{at}med.kuleuven.be