CONTRACTILE DYSFUNCTION OF ISOLATED VENTRICULAR MYOCYTES IN EXPERIMENTAL UREMIA

In order to clarify the mechanism underlying impaired cardiac performa nce 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 procedu re, and left for 4 weeks. Sham-operated controls were prepared at the same time. Animals were pair-fed, and final body weights were not sign ificantly different between the groups. Ventricular myocytes were isol ated and their contraction amplitude and velocity were measured using a video-based edge-detection system. Contraction was depressed in myoc ytes from uraemic animals, with contraction amplitude in maximum Ca2reduced 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 v elocity of shortening (5.6 +/- 0.4 vs, 3.9 +/- 0.5 mu m s(-1) change i n sarcomere length, p < 0.02) and of relaxation (4.6 +/- 0.4 vs, 3.2 /- 0.4 mu m s(-1) p < 0.02). Similar depression was seen at lower perf usate Ca2+ concentrations (1-2 mM) and the EC(50) for Ca2+ was unchang ed. The response to beta-adrenoceptor stimulation was decreased by the same magnitude as that to Ca2+, with no change in the EC(50) for isop roterenol or the ratio of maximum response to isoproterenol or to Ca2 in the same cell (isoproterenol/Ca2+ ratio). There was no shift in th e myosin isozyme composition in uraemic cells, with both groups showin g a heterogeneous V1/V2/V3 pattern. We conclude that chronic uraemia i s associated with a depression of contractile function in the isolated myocyte but no shift in myosin isoforms or specific beta-adrenoceptor desensitisation.