Role and significance of plasma citrulline in the early phase after small bowel transplantation in pigs

Abstract

Summary A reliable serological marker of acute cellular rejection (ACR) after small bowel transplantation (SBTx) is still missing. Plasma citrulline level (PCL) reflects the functional integrity of intestinal mucosa which is partially lost during ACR. The aim of our study was to investigate the role of PCL as marker of ACR after SBTx. Eighteen German landrace pigs were used and divided into three groups. Group 1 (G1), autologous SBTx (n = 4) as control; group 2 (G2), allogeneic SBTx without immunosuppression (IS) (n = 7) and group 3 (G3), allogeneic SBTx with IS (n = 7). IS consisted of tacrolimus and steroids without induction treatment. Observation period was 14 days. Mucosal biopsies were obtained intraoperatively and daily using a Thiry–Vella loop. ACR was differentiated into indeterminate, mild, moderate and severe using a standardized grading schema. PCL was measured daily. An ACR onset occurred generally from postoperative day 4 both in G2 and G3 as mild form and developed differently in the two groups: moderate to severe in G2 and indeterminate to mild in G3. A significant decline of PCL occurred only in cases of moderate and severe ACR, but not in cases of indeterminate and mild ACR. The PCL failed as a marker in the early diagnosis of ACR and became reliable only when advanced mucosal damage was present.

Plasma citrulline levels and acute cellular rejection early after small bowel transplantation in pigs

“…Recently, in Nadalin's experimental study, the results suggested that measurement of the plasma citrulline level could be useful as a marker of rejection (Nadalin et al, 2007). However, the plasma level of citrulline was not sufficient for identifying a mild form of ACR in this experiment.…”

Review of Various Techniques of Small Bowel Transplantation in Pigs

“…Other forms of application [20,21] or no heparinization at all [11,17,22,23] have been reported as well. Both systemic [5, 10-12, 16, 21, 22, 24] perfusion and flushing of the bowel during back-table procedures [4,14,15,25] have been described. Systemic perfusion of the graft is mainly performed by cannulating the infrarenal aorta [5, 10-12, 16, 21, 22, 24].…”

“…Systemic perfusion of the graft is mainly performed by cannulating the infrarenal aorta [5, 10-12, 16, 21, 22, 24]. In case of ex situ flushing, it is performed through the SMA [4,14,15,[24][25][26][27]. In most models, iced Lactated Ringers Solution [4,12,17,24,25,27] or University of Wisconsin Solution is used as perfusion solution [7,11,13].…”

“…The mode of application and the dosage vary widely. It is common to carry out a systemic heparinization of the donor after preparation of bowel and vessels and before crossclamping the vascular supply of the graft [12][13][14][15][16]. The applied dosage of heparin is 100 [17] -300 [13] IU/Kg or 2000 [5,12] -5000 IU [15].…”

Tetrandrine ameliorated reperfusion injury of small bowel transplantation

“…Although most studies concerning intestinal reperfusion injury used in situ warm ischemia models, the results cannot be directly extrapolated to the reperfusion injury associated with intestinal transplantation, which consists of both cold and warm ischemia. Furthermore, the changes in the intestinal mucosa induced by reperfusion injury are noted to begin intraoperatively and vanish within 1 to 2 days after the operation [20]; thus, in this study, we explored the effects of tetrandrine on intestinal reperfusion injury in pigs during the first 24 hours after small bowel transplantation and explored the underlying mechanisms of the actions of the drug. …”