ARGININE, FISH-OIL, AND DONOR-SPECIFIC TRANSFUSIONS INDEPENDENTLY IMPROVE CARDIAC ALLOGRAFT SURVIVAL IN RATS GIVEN SUBTHERAPEUTIC DOSES OF CYCLOSPORINE

Background: Dietary supplementation with a fish oil and arginine-enric hed immunoenhancing diet (Impact; Sandoz Nutrition, Minneapolis, MN) i n a rat cardiac allograft model using donor-specific transfusion (DST) and cyclosporin (CsA) resulted in significant prolongation of cardiac allograft survival with many animals developing long-term tolerance. This study was done to determine whether arginine or fish oil was the active ingredient. Methods: A standard AIN-76A diet was modified to in clude either 10% fish oil, 2% arginine, or 5% arginine with or without fish oil. Diets were fed to Lewis strain rats that received Ax C9935 Irish (ACI) heterotopic cardiac allografts beginning on day 1 and cont inuing indefinitely. A DST (1.0 mL ACI whole blood) was given with 10 mg/kg CsA on day 1 relative to transplant and 2.5 mg/kg/d on days 0 to 6. Groups of animals receiving AIN-76A diet fortified with 2% glycine and animals receiving a DST or DST/CsA and regular laboratory chow se rved as controls. Results;: Mean survival times +/- SEM in days were a s follows: untreated, 7.1 +/- 0.4; CsA/2% glycine, 8.5 +/- 0.6; DST on ly, 9.6 +/- 1.1; DST/CsA, 26.6 +/- 6.4; CsA/2% arginine, 25.5 +/- 3.9; DST/CsA/2% arginine, 68.7 +/- 8.9; DST/CsA/5% arginine, 90.1 +/- 31.1 ; CsA/fish oil, 73.6 +/- 26.1; and DST/CsA/fish oil/5% arginine, 90.1 +/- 31.1. The effect of arginine was slightly dose dependent and was s een best in combination with DST, but the effect of fish oil was not e nhanced by DST. Conclusions: Both fish oil and arginine dietary supple mentation significantly improved allograft survival but through differ ent mechanisms (DST vs non-DST dependent).