Arginine, fish oil, and donor-specific transfusions independently improve cardiac allograft survival in rats given subtherapeutic doses of cyclosporin.

Abstract

Dietary supplementation with a fish oil and arginine-enriched immunoenhancing diet (Impact; Sandoz Nutrition, Minneapolis, MN) in 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. A standard AIN-76A diet was modified to include 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 continuing 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 served as controls. Mean survival times +/- SEM in days were as follows: untreated, 7.1 +/- 0.4; CsA/2% glycine, 8.5 +/- 0.6; DST only, 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 seen best in combination with DST, but the effect of fish oil was not enhanced by DST. Both fish oil and arginine dietary supplementation significantly improved allograft survival but through different mechanisms (DST vs non-DST dependent).