Myocyte function and [Ca 2+ ]i homeostasis during early allogenic heart transplant rejection

• Published in: Transplantation Vol. 72; no. 10; p. 1603
• Main Authors: Ritter, M, Su, Z, Yao, A, Zubair, I, Xu, S, Shelby, J, Barry, W H
• Format: Journal Article
• Language: English
• Published: United States 27.11.2001
• Subjects: Animals; Arginine - pharmacology; Calcium - metabolism; Cyclic GMP - physiology; Graft Rejection - physiopathology; Heart Transplantation - immunology; Homeostasis; Isoproterenol - pharmacology; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Myocardial Contraction - drug effects; Nitric Oxide Synthase - physiology; Transplantation, Homologous
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/00007890-200111270-00005

Recent studies from our laboratory have demonstrated that in vivo contractile function of rejecting mouse heterotopic abdominal heart allografts 5 days after transplantation is depressed to 40% of that of syngenic controls, and that this depression of function is prevented by the nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine. However, the mechanisms of altered myocyte function caused by nitric oxide production in this setting are not established. We measured intracellular calcium concentration ([Ca2+]i) transients (fluo-3, confocal microscopy), fractional shortening (video motion), and L-type Ca2+ currents (whole-cell patch clamp) 5 days after transplantation in ventricular myocytes freshly isolated from syngenic (Balb/C into Balb/C) and allogenic (Balb/C into C3H) transplants. L-type Ca2+ currents, [Ca2+]i transient amplitudes, and fractional shortening did not differ between nonrejecting, syngenic and rejecting, allogenic transplants. Catecholamine responsiveness as analyzed by the change in the peak [Ca2+]i transient induced by 100 nM isoproterenol was also similar. Superfusion with l-arginine, an NOS substrate, caused decreased shortening with no change in [Ca2+]i transients in allogenic myocytes, but had no effect in syngenic myocytes. Depressed contractile function of rejecting allogenic heart transplants in vivo appears to be caused in part by an NOS-dependent decrease in myofilament Ca2+ sensitivity.