FUNCTIONAL-STUDIES ON THE HUMAN TRANSPLANTED SMALL-INTESTINE

Intestinal transplantation is currently under development for treatmen t of short bowel syndrome. It was our purpose to examine the release o f inflammatory mediators in a 1-year-old child with congenital agangli onosis following small intestinal transplantation (ligament of Treitz to colon; ileostomy). After obtaining institutional and parental conse nt, studies were performed at the 6th, 7th and 8th week after surgery and while the patient was receiving enteral nutrition (human breast mi lk). Prior to each investigation the ileal mucosa was examined endosco pically and biopsies were obtained. A 3-cm segment of ileum was isolat ed between balloons and perfused with an isoosmolar solution at 2 ml/m in at 37-degrees-C. Effluents were analyzed for: albumin, histamine, h yaluronan (hyaluronic acid), eosinophilic cationic protein (ECP) and P GE2. Although control values were unavailable in infants, data obtaine d from the adult jejunum served as control. Endoscopically the mucosa revealed loss of valvulae conniventes and progressive aphthous to deep mucosal ulcerations. Histologically this was detected as increased nu mber of mononuclear cells, edema and fibrosis. After transplantation t he appearance rate of histamine and ECP were low, but increased progre ssively. PGE2 was markedly increased at the start of the studies (5566 pg/cm/h compared to 11.7 +/- 3.0 in controls, mean + SEM; n = 35), bu t did not profoundly increase further. Albumin and particularly hyalur onan, however, increased more than 30-fold versus controls (21420 mug/ cm/h vs controls 669 +/- 46, n = 66 and 20558 ng/cm/h vs controls 660 +/- 44, n = 66, respectively) in line with clinical deterioration. We conclude: 1) The technique for segmental intestinal perfusion can be u sed to monitor inflammatory mediators and mucosal leakage in a small b owel allograft. 2) The transplanted small intestine undergoes progress ive ulceration associated with histological fibrosis; and, 3) The exce ssive accumulation of interstitial hyaluronan can influence water tran sport and thereby also intestinal circulation.