IMPAIRED SURVIVAL AND GROWTH IN IMMUNOSUPPRESSED YOUNG-RATS WITH LETHAL SHORT GUT SYNDROME AND A SMALL-BOWEL TRANSPLANT - AN EFFECT OF CYCLOSPORINE

Neonates and growing individuals have increased nutritional demands as compared with adults. To determine the functional ability of an intes tinal graft to allow survival and growth, an otherwise lethal short gu t model should be used (resection of both the entire small bowel and t he cecum). In this study the authors investigated the survival and gro wth in young rats (80 to 125 gl with this lethal short gut syndrome (S GS) and either syngeneic or allogeneic segmental small bowel transplan tation (SBTx). Additionally they sought to determine the effect of the rapeutical doses of cyclosporine (CyA) in young, growing rats, To avoi d total parenteral nutrition in rats undergoing SBTx, surgery was carr ied out in two steps: after segmental SBTx of a 25-cm jejunal graft, S GS was created 2 weeks later. Lewis rats underwent 1: Syngeneic segmen tal SBTx + SGS (pr = 7); 2: Allogeneic segmental SBTx (donor: Lewis Br own Norway F-1) + SGS + CyA (15 mg/kg/d for 7 days, then every other d ay for 21 days) (n = 9); 3: Syngeneic segmental SBTx + SGS + CyA as in group 2 (9 = 5); 4: SGS alone in = 5): 5: small bower resection alone In = 5); 6: sham laparotomy twice (9 = 5); 7: sham laparotomy twice CyA as in group 2 (n = 6). Weight, general condition, and nutritional serum variables were followed up regularly for 4 months. Rats with re section of small bower survived but did not grow. Rats with small bowe l resection + cecectomy died within 5 days. Sham-operated rats had a n ormal weight development compared with CyA-treated sham-operated rats who grew significantly slower (P <.05). Rats with syngeneic SBTx and S GS survived and grew consistently. Rats with syngeneic or allogeneic S BTx, SGS + CyA treatment had poor weight development and died within 2 weeks after the short gut procedure. Compared with sham-operated rats , CyA-treated sham-operated rats had lower levels of albumin end trigl ycerides (P <.05) and higher levels of urea and creatinine (P <.05). T hese results suggest that the short gut model used is indeed lethal an d that syngeneic segmental SBTx permits survival and growth in young r ats with this lethal SGS. They also suggest that when given over a 4-w eek period, a standard dose of CyA impairs growth in young rats, and t hat this may be caused by the intestinal and renal side effects of CyA . Lastly, we attribute the failure of CyA treated rats with SBTx and S GS to survive and grow in great part to the side effects of CyA. Copyr ight (C) 1995 by W.B. Saunders Company