Liver transplantation in man. Gastrointestinal perfusion and inflammatory response

Abstract

Patients undergoing liver transplantation develop a systemic inflammatory response which eventually continues with development of a multiple organ dysfunction syndrome (MODS). Gastro-intestinal hypoxia or bacterial translocation has been proposed as the "motor" of MODS. This thesis examines the inflammatory response in patients undergoing liver transplantation with focus on regional gastro-intestinal perfusion and inflammatory response. Fifty-four patients undergoing liver transplantation were studied. Gastro-intestinal perfusion was measured with gastric tonometry and jejunal endoluminal laser-Doppler flowmetry. Arterial blood plasma concentrations of PMN elastase and TNF-a, interleukin 1-b, interleukin 6, interleukin 8 were measured. Complement C3a, C5a, SC5b-9 and endotoxin were measured simultaneously in arterial and portal vein blood. Gastric intramucosal pH decreased during the dissections phase and anhepatic phase, but there were only minor changes in tonometric PCO2 and tonometric-arterial PCO2 gradient. Jejunal perfusion was characterised by a progressive decrease during the anhepatic phase and an increase after reperfusion. Plasma concentrations of TNF-a and interleukin 1-b were low throughout the study period. Plasma concentrations of interleukin 6, interleukin 8 and PMN-elastase increased significantly after reperfusion. The C3a plasma concentrations were higher in the portal vein compared to the radial artery. Gastro-intestinal SC5b-9 release was associated with higher postoperative concentrations of aspartate aminotransferase and alanineaminotransferase, lower concentrations of factor II-VII-X and prolonged ICU stay compared to patients without gastro-intestinal SC5b-9 release. Endotoxin concentrations in arterial and portal venous blood were low and the association between endotoxaemia and complement activation was poor. The results demonstrate that although jejunal perfusion measured by laser-Doppler flowmetry is transiently decreased during liver transplantation gastro-intestinal perfusion measured by gastric tonometry is in the range of aerobic metabolism. During liver transplantation there is activation of complement and neutrophils, and systemic release of pro-inflammatory cytokines. Gastro-intestinal complement activation is associated with postoperative parenchymatous liver cell injury and liver dysfunction.