title: Excitation-contraction coupling and contractile protein function in failing and nonfailing human myocardium.
abstract: Isometric force, heat output, and aequorin light emission were measured in isolated muscle strips from nonfailing human hearts and from hearts with endstage failing dilated cardiomyopathy (37 degrees C; 30-180 beats per minute (bpm)). In nonfailing myocardium, peak twitch tension increased with higher rates of stimulation, whereas the force-frequency relation was inverse in the failing myocardium. At 60 bpm and at higher rates of stimulation, peak twitch tension was reduced significantly in the failing myocardium. Myothermal measurements, performed at 60 bpm, indicated that the number of crossbridge interactions and the amount of calcium cycling are reduced significantly in the failing myocardium. Furthermore, aequorin light transients indicated that the inverse force-frequency relation in failing myocardium results from altered calcium cycling; with increasing rates of stimulation aequorin light emission increased continuously in the nonfailing and decreased continuously in the failing myocardium. The data suggest that impaired myocardial performance in failing human myocardium may result primarily from disturbed excitation-contraction coupling processes with a reduced amount of calcium cycling and, thus, a decreased activation of contractile proteins.
authors.affiliation: Medizinische Klinik III, Universität Freiburg, FRG.
authors.forename: G
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: B
authors.initials: B
authors.lastname: Pieske
authors.forename: C
authors.initials: C
authors.lastname: Holubarsch
authors.forename: N R
authors.initials: NR
authors.lastname: Alpert
authors.forename: H
authors.initials: H
authors.lastname: Just
mesh_terms: D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000503:physiopathology*; D003285:Contractile Proteins / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000502:physiology*; D012016:Reference Values
chemical_list: D003285:Contractile Proteins; D002118:Calcium