title: From overload to failure: what happens inside the myocyte.
abstract: To determine whether there is a defect in the surviving muscle cells of the failing human heart, studies have been performed on individual myocytes isolated from normal and failing human myocardium. Myocytes from the failing ventricle contract and relax more slowly, and have a reduced contraction amplitude at physiological (but not low) stimulation frequencies. Slow relaxation is seen irrespective of the aetiology of the heart disease studied, and is more pronounced in myocytes from hypertrophied ventricles. Myocytes from hypertrophied ventricles are larger than normal, but the relaxation deficit is independent of cell size. Beta-adrenoceptor desensitization is evident in myocytes and it varies according to the severity of disease and with the age of the patient. Action potentials are longer in myocytes from failing human heart, probably because of an alteration in K+ current density. Many of the functional changes identified in failing human myocardium are seen at the level of the single cardiac myocyte, which implies that pharmacological or genetic manipulation of surviving cells is a logical therapeutic strategy.
authors.affiliation: National Heart and Lung Institute, Imperial College School of Medicine, London, UK. sian.harding@ic.ac.uk
authors.forename: S E
authors.initials: SE
authors.lastname: Harding
authors.forename: K
authors.initials: K
authors.lastname: Davia
authors.forename: C H
authors.initials: CH
authors.lastname: Davies
authors.forename: F
authors.initials: F
authors.lastname: del Monte
authors.forename: A R
authors.initials: AR
authors.lastname: Money-Kyrle
authors.forename: P A
authors.initials: PA
authors.lastname: Poole-Wilson
mesh_terms: D000200:Action Potentials; D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000503:physiopathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011930:Reaction Time