The Failing Cardiomyocyte

Abstract

This article presents an integrated account of the subcellular alterations underlying each of the main observed defects in function of the ventricular cardiomyocytes from failing human heart: poor contraction, slow relaxation, β-adrenoceptor desensitization, and tendency to arrhythmia. The key role of the β-adrenoceptor system is highlighted: loss of tonic support from cyclic AMP-stimulated pathways contributes to the contraction and relaxation defects observed, but it is residual β-adrenoceptor function that exacerbates arrhythmias. Most of the alterations are “acquired” during the process of adaptation of the heart to cell loss, and are common to various etiologies of heart failure. Information gained from studies on genetic causes of cardiomyocyte malfunction, however, has been instructive in the interpretation of the functional effects of subcellular alterations.