An inbred rat model of small bowel transplantation was used to study the metabolic consequences of systemic venous drainage of the graft. Lewis rats received either Lewis (isograft) or Lewis X Brown Norway F1 (allograft) small bowel grafts. Venous drainage of the isografts was to either the portal vein or the inferior vena cava. Allograft recipients underwent systemic venous drainage and were treated with a 4-week course of tapering cyclosporine. Ammonia levels in systemically drained isografts (108 ± 5 μM/100 ml) were more than twice those in portally drained isografts (38 ± 3, P < 0.001), while amino acid analysis showed significant elevations in glycine, serine, asparagine, histidine, phenylalanine, and tyrosine. Ammonia levels decreased and amino acid alterations were generally corrected when animals were fed a modified protein diet low in aromatic and high in branched chain amino acids. Recipients of both systemically and portally drained isografts grew normally, while weight gain in allograft recipients was impaired. We conclude that (1) systemic venous drainage of small bowel grafts results in altered ammonia and amino acid levels that resemble those found in models of hepatic encephalopathy; (2) these changes can be significantly ameliorated by dietary modification; and (3) the compromised growth seen in systemically drained allografted animals results from chronic rejection and/or cyclosporine rather than the partial porto-systemic shunt.
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