title: Functional and structural impairment in human, rat and guinea-pig atrial muscle in response to in vitro calcium overload: a cytochemical study on cellular calcium distribution.
abstract: Critical accumulation of cellular calcium in ischaemic myocardium is involved in irreversible cell damage. In human right atrial trabeculae and in rat and guinea-pig left atria, we investigated whether direct calcium overload by increasing the extracellular calcium concentration, [Ca2+]o, leads to similar impairment of function and ultrastructure as observed after ischaemia. The force of contraction was measured during two consecutive cumulative increases in [Ca2+]o (1-25 mmol/l) separated by 30 min of incubation at low [Ca2+]o. Compared to the first Ca2+ challenge, the positive inotropic effect of increasing [Ca2+]o was depressed during the second one and the after-contractions, and the increase in resting tension developing with high [Ca2+]o tended to be larger. The ultrastructure of the tissue fixed immediately after excision was well preserved. When fixed after the second Ca2+ challenge, half of the cells were severely damaged with various signs of cellular Ca2+ overload similar to those observed after ischaemic damage: the sarcolemma lost its Ca(2+)-binding properties, sarcomeres showed contraction band necrosis, the mitochondria had disrupted cristae and contained either large clusters of Ca2+ precipitate or amorphous densities (Jennings granules). In many cells, calcium precipitates were present in the cytoplasm. The morphological and functional changes were similar in the three species studied. Our results suggest that the deterioration of atrial myocardium after challenge with high [Ca2+]o or after severe ischaemia may be traced back to a common mechanism, i.e. the sarcolemma loses its competence as a permeable barrier for Ca2+ and therefore facilitates excessive Ca2+ entry. However, for the direct demonstration of calcium precipitates as a sign of cytosolic Ca2+ overload, high [Ca2+]o are required with are not normally present in the myocardium.
authors.affiliation: Department of Pharmacology, University of Essen, West Germany.
authors.forename: G S
authors.initials: GS
authors.lastname: Liu
authors.forename: U
authors.initials: U
authors.lastname: Ravens
authors.forename: V
authors.initials: V
authors.lastname: Sadony
authors.forename: G
authors.initials: G
authors.lastname: Vandeplassche
authors.forename: M
authors.initials: M
authors.lastname: Borgers
mesh_terms: D000818:Animals; D016275:Atrial Function / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002463:Cell Membrane Permeability; D006168:Guinea Pigs; D006651:Histocytochemistry; D006801:Humans; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D008928:Mitochondria / Q000473:pathology; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D012508:Sarcolemma / Q000473:pathology; D012518:Sarcomeres / Q000473:pathology
chemical_list: D002118:Calcium