EFFECT OF TACROLIMUS ON HEMODYNAMICS AND ABSORPTION OF EXPERIMENTAL SMALL-INTESTINAL TRANSPLANTS

We have previously reported the adverse effects of cyclosporine on sma ll intestine transplant physiology. In this study, we report for the f irst time the effect of tacrolimus (FK) on graft intestinal blood flow and intramural distribution, vascular resistance, and absorptive func tion. Isogeneic small intestine transplantation was performed in Lewis rats. Animals were grouped based upon the following treatment schedul es: no treatment for 1 week in group 1; 0.6 ml/kg/day i.m. polyethylen e glycol (PEG) for 1 week in group 2; 2 mg/kg/day i.m. FK for 1 week i n group 3; 0.6 ml/kg/day PEG for 1 week and then 0.3 ml/kg/day for 5 w eeks in group 4; 2 mg/kg/day FK for 1 week and then 1 mg/kg/ day for 5 weeks in group 5. Group 6 was the same as in group 5 but FK was withd rawn for 1 week prior to assessment. Maltose absorption was measured t o evaluate graft absorptive function. Blood flow and its intramural di stribution to mucosal and serosal/muscularis layers were determined us ing the radioactive microsphere technique. Perfusion pressure was meas ured to calculate vascular resistance. One week of FK administration i n group 3 did not change graft hemodynamics and absorption significant ly. Prolonged FK treatment up to 6 weeks in group 5 resulted in a sign ificant increase in mucosal vascular resistance (71.0+/-9.6 versus 47. 7+/-6.7 U/g, P<0.01) and significant decreases in mucosal blood flow ( 1.14+/-0.15 versus 1.69+/-0.24 ml/g/min, P<0.01) and maltose absorptio n (30 min after loading: 155.4+/-26.9 versus 216.4+/-29.6, P<0.01; 60 min after loading: 172.9+/-24.5 versus 229.1+/-32.6 glucose mg/dl P<0. 01). The serosal/muscularis layer remained relatively unaffected. With drawal of FK for 1 week after prolonged treatment in group 6 resulted in restorations of all parameters measured to normal ranges. We conclu de that a short course of FK is safe, but prolonged FK administration has harmful effects on the hemodynamics and function of small intestin al transplants. Complete recovery is achieved when FK is discontinued.