Intramucosal pH and liver endotoxin clearance during experimental liver transplantation.

The study was designed to assess the gastrointestinal ischaemia and the influence of the specific Kupffer cell toxin gadolinium chloride (GdCl3) on the hepatic and extrahepatic endotoxin [lipopolysaccharide (LPS)] clearance during experimental orthotopic liver transplantation (OLT) in pigs. In eight pig liver transplantations, the donors received 20 mg/kg of GdCl3 24 h before explantation, while controls (n = 8) received normal saline. Gastric and sigmoid intramucosal pH (pHi), LPS and endotoxin-neutralising capacity (ENC) levels were measured in the portal vein and superior vena cava after laparatomy, at the end of the anhepatic phase and 1 h after reperfusion. During the anhepatic phase, the sigmoid pHi decreased significantly from 7.32 +/- 0.02 to 7.29 +/- 0.03 (P < 0.001) and was associated with a substantial increase of portal LPS. Following reperfusion, the systemic LPS concentrations were significantly lower in the pretreated group [39 +/- 23 pg/ml (Control); 14 +/- 7 (GdCl3); P < 0.05] suggesting an improved liver LPS clearance [86% (GdCl3); 58.2% (Control); P < 0.05]. This corresponded to an increased ENC in the pretreated group [118 +/- 52 ENU/ml (GdCl3) vs 81 +/- 45 ENU/ml (Control); P < 0.05]. The anhepatic phase induced splanchnic ischaemia which correlated with portal endotoxaemia. Donor preconditioning with GdCl3 leads to lower systemic LPS concentrations in the recipient and increases ENC values in the early phase after OLT. An improved hepatocellular LPS extraction and/or an activation of the extrahepatic reticulo-endothelial system as a result of GdCl3 treatment is discussed.

Effects of exogenous endothelin-1 application on liver perfusion in native and transplanted porcine livers.

PURPOSE: This study was designed to assess and differentiate the impact of progressivly increasing portal venous endothelin-1 (ET) plasma concentrations on hepatic micro- and macroperfusion of native porcine livers (Group A) and liver grafts after experimental transplantation (Group B). METHODS: A standardized gradual increment in systemic ET plasma concentration (0-58 pg/ml) was induced by continuous ET-1 infusion into the portal vein in both groups (A: n = 10, B: n = 10). Control animals received only saline (n = 5, each group). Hepatic microcirculation (HMC) was quantified by thermodiffusion electrodes, hepatic artery flow (HAF), and portal venous flow (PVF) by Doppler flowmetry. RESULTS: No changes in ET or perfusion parameters were observed in controls. The mean ET level after orthotopic liver transplantation (OLT) in Group B was elevated (baseline: 3.8 +/- 2.4 pg/ml) compared with Group A (2.8 +/- 1.9 pg/ml). With rising ET levels HAF decreased progressively in Group A from 205 +/- 97 (baseline) to 160 +/- 72 ml/min, and in Group B from 161 +/- 87 to 146 +/- 68 ml/min. PVF decreased in Group A from 722 +/- 253 to 370 +/- 198 ml/min, and in Group B from 846 +/- 263 to 417 +/- 203 ml/min. Baseline HMC in Group A was 86 +/- 15 and decreased significantly to 29 +/- 9 ml/100 g/min, and baseline MC in Group B was 90 +/- 22 and decreased to 44 +/- 32 ml/100 g/min. No significant alteration in systemic circulation was noted at the ET concentrations investigated. CONCLUSIONS: Significant impairment of hepatic micro- and macrocirculation was detected after induction of systemic ET levels above 9.4 pg/ml both in native and in transplanted livers. Disturbance of HMC was caused predominantly by reduction of portal venous flow, while the effect of ET on HAF was less pronounced. Characteristics of flow impairment in transplanted and native livers were analogous after short cold ischemic graft storage (6 h).

Microchimerism in bone marrow-derived CD34(+) cells of patients after liver transplantation.

Lymphoid and dendritic cells of donor origin can be detected in the recipient several years after a solid organ transplantation. This phenomenon is termed microchimerism and could play a role in the induction of tolerance. The fate of other hematopoietic cells transferred by liver transplantation, in particular of stem and progenitor cells, is unknown. For this reason, we studied peripheral blood and bone marrow samples of 12 patients who had received a liver transplant from an HLA-DR mismatched donor. Eight patients were long-term survivors between 2.8 and 10.1 years after allografting. CD34(+) cells from bone marrow were highly enriched with the use of a 2-step method, and a nested polymerase chain reaction was applied to detect donor cells on the basis of allelic differences of the HLA-DRB1 gene. Rigorous controls with DRB1 specificities equal to the donor and host were included. In 5 of 8 long-term liver recipients, donor-specific CD34(+) cells could be detected in bone marrow. Microchimerism in the CD34(+) cell fraction did not correlate to the chimeric status in peripheral blood. In conclusion, our results demonstrate a frequent microchimerism among bone marrow-derived CD34(+) cells after liver transplantation. The functional role of this phenomenon still needs to be defined. (Blood. 2000;96:763-767)

[Sandostatin treatment in postoperative external digestive fistulae]. / Tratamentul cu Sandostatin în fistulele digestive externe postoperatorii.

The aim of the conservative treatment of postoperative external digestive fistulae is to obtain a reduction of the output, thus favoring spontaneous closure and shortening outcome. A retrospective comparative study has been performed on two groups of patients with postoperative anastomotic gastrointestinal and pancreatic fistulae. Group A included 18 cases (14 anastomotic, 4 pancreatic fistulae) receiving conventional treatment only. Group B included 25 cases (18 anastomotic and 7 pancreatic fistulae) in which Sandostatin was associated to conventional therapy, using daily doses ranging from 0.1 mg to 0.3 mg, administered after variable intervals after fistulas' occurrence. Duration of treatment ranged from 1 to 25 days. In group A, 27.77% of the cases were cured in comparison with group B in which the healing rate increased to 56%. Global hospital mortality rate was 25.58% (11 cases). In group A this was 44.44% (8 cases) in comparison with group B with 12% (3 cases) only. As a conclusion of our study, the use of Sandostatin is remarkable effective in the treatment of external digestive postoperative fistulae. Thus a doubling of healing rate and a reduction by 73% of mortality rate was achieved.