title: Contractile dysfunction of isolated ventricular myocytes in experimental uraemia.
abstract: In order to clarify the mechanism underlying impaired cardiac performance in uraemia, the contractile function of isolated cardiac myocytes from chronically uraemic and control rats has been compared. Rats were made uraemic by sub-total nephrectomy in a two-stage surgical procedure, and left for 4 weeks. Sham-operated controls were prepared at the same time. Animals were pairfed, and final body weights were not significantly different between the groups. Ventricular myocytes were isolated and their contraction amplitude and velocity were measured using a video-based edge-detection system. Contraction was depressed in myocytes from uraemic animals, with contraction amplitude in maximum Ca2+ reduced from 16.3 +/- 0.6% shortening, to 13.0 +/- 0.8% (p < 0.01, n = 10 animals for each group). There was a concomitant decrease in the velocity of shortening (5.6 +/- 0.4 vs. 3.9 +/- 0.5 micron s-1 change in sarcomere length, p < 0.02) and of relaxation (4.6 +/- 0.4 vs. 3.2 +/- 0.4 micron s-1 p < 0.02). Similar depression was seen at lower perfusate Ca2+ concentrations (1-2 mM) and the EC50 for Ca2+ was unchanged. The response to beta-adrenoceptor stimulation was decreased by the same magnitude as that to Ca2+, with no change in the EC50 for isoproterenol or the ratio of maximum response to isoproterenol or to Ca2+ in the same cell (isoproterenol/Ca2+ ratio). There was no shift in the myosin isozyme composition in uraemic cells, with both groups showing a heterogeneous V1/V2/V3 pattern. We conclude that chronic uraemia is associated with a depression of contractile function in the isolated myocyte but no shift in myosin isoforms or specific beta-adrenoceptor desensitisation.
authors.affiliation: Department of Nephrology, St. Bartholomew's Hospital, London, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: McMahon
authors.forename: G
authors.initials: G
authors.lastname: Vescovo
authors.forename: L
authors.initials: L
authors.lastname: Dalla Libera
authors.forename: D G
authors.initials: DG
authors.lastname: Wynne
authors.forename: R J
authors.initials: RJ
authors.lastname: Fluck
authors.forename: S E
authors.initials: SE
authors.lastname: Harding
authors.forename: A E
authors.initials: AE
authors.lastname: Raine
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D009218:Myosins / Q000378:metabolism; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000097:blood; D014511:Uremia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*
chemical_list: D014508:Urea; D003404:Creatinine; D009218:Myosins; D000252:Calcium-Transporting ATPases; D007545:Isoproterenol; D002118:Calcium