Prolonged Use of Cyclosporine (CsA) Produces Reversible Hemodynamic and Absorptive Alterations in the Transplanted Rat Small Intestine

Abstract

Cyclosporine (CsA)-induced alterations in organ blood flow (BF) and function have been studied in kidney and pancreatic transplants. In this study, we assessed the effect of prolonged CsA administration on graft tissue BF and absorption from transplanted rat small intestine (SI). Isogeneic SI transplantation was performed in Lewis rats. Animals were grouped based upon the following treatment schedules: no treatment for 1 week in group 1; 0.15 ml/kg/day im olive oil for 1 week in group 2; 0.15 ml/kg/day olive oil for 1 week and then 0.1 ml/kg/day for 5 weeks in group 3; 15 mg/kg/day im CsA for 1 week in group 4; and 15 mg/kg/day CsA for 1 week and then 10 mg/kg/day for 5 weeks in group 5. Group 6 was the same as group 5 but CsA was withdrawn for 1 week prior to assessment. Maltose absorption was measured to evaluate graft absorptive function. BF and its intramural distribution to mucosal and serosal/muscularis layers were determined using the radioactive microsphere technique. Perfusion pressure was measured to calculate vascular resistance (VR). One week of CsA of administration in group 4 resulted in a significant increase in mucosal VR (68.4 ± 15.5 versus 46.9 ± 8.7 U/g, P < 0.01) and significant decreases in mucosal BF (1.21 ± 0.25 versus 1.80 ± 0.38 ml/g/min, P < 0.01) and maltose absorption 30 min after loading (168.9 ± 21.1 versus 214.4 ± 28.4 glucose mg/dl, P < 0.01). Prolonged CsA treatment up to 6 weeks in group 5 resulted in further increases in whole intestinal VR (88.6 ± 19.1 versus 70.1 ± 12.4 U/g, P < 0.05) and decreases in whole intestinal BF (0.93 ± 0.18 versus 1.16 ± 0.18 ml/g/min, P < 0.05) and maltose absorption 39 min after loading (137.4 ± 21.3 versus 168.9 ± 21.1 glucose mg/dl) when compared with 1 week of CsA treatment in group 4. Withdrawal of CsA for 1 week after prolonged CsA treatment in group 6 resulted in restorations of VR in both mucosal and serosal/muscularis layers, BF in serosal/muscularis layer, and absorptive function to the normal ranges as shown in group 3 (P = NS). We concluded that CsA administration causes hemodynamic alterations in the intestinal vascular system and dose-dependent functional impairment which are reversible when CsA is discontinued.