EXPERIMENTAL ARTERIAL ALLOGRAFTING UNDER LOW AND THERAPEUTIC DOSAGES OF CYCLOSPORINE FOR IMMUNOSUPPRESSION

The aim of this study was to investigate performance of preserved arte rial allografts under the protection of a high-dose and a low-dose imm unosuppressive regimen, with cyclosporine (CsA), Dog carotid arteries were harvested and stored for 14 days at 4 degrees C in University of Wisconsin organ preservation solution, Segments (6 cm) of carotid arte ry were orthotopically and bilaterally implanted in mongrel dogs (n=18 ), CsA was given in two dosage regimens: 25 mg/kg/day (group I, n=7) a nd 10 mg/kg/day (group II, n=7), The control group received no CsA (gr oup III, n=4). After 3 months of implantation, patency was assessed by angiography. The grafts were excised for investigation of vessel wall and endothelial function and morphology, For assessment of function i n vitro, slices of arterial segments were connected as ring preparatio ns to an isometric force transducer and immersed in a 5 ml organ bath (37 degrees C) containing Tyrode's solution, The contractile response was examined by adding 40 mM KCl and phenylephrine (100 mu M) to the o rgan bath; endothelium-dependent relaxation was examined by adding met hacholine (100 mu M). Morphology was assessed semiquantitatively, The functional responses to KCl, phenylephrine (Phe) and methacholine (Met ) after 14 days of storage in UW, were 30.2+/-1.2 mN, 26.9+/-1.0 and 4 5+/-1.2% (means +/- SEM, n=9), respectively, Patency after three month s of implantation for group I was 100% (14/14), for group II 50% (7/14 ), and for group III 75% (6/8), In vitro functional responses of prese rved arteries, after 3 months of implantation in group I were 58.5+/-1 0.6 mN (KCl), 36.5+/-5.8 mN (Phe), and 57.4+/-9.7% (Met), respectively . Functions in group II were 1.2+/-0.1 mN (KCl), 0.0 mN (Phe), and 0.0 % (Met). Grafts in group III showed no function. Measurement of medial thickness showed significant thinning (P<0.05) in groups II and III. Patency and function of arterial allografts under a therapeutic dose o f CsA were superior to grafts implanted under low-dose CsA or no immun osuppressive treatment.