Do Splanchnic Viscera Contribute to Liver Preservation Reperfusion Injury?

Abstract

Preservation-reperfusion injury of hepatic allografts is thought to be associated with Kupffer cell activation and TNF release from the transplanted organ. Confirmation that the allograft is the source of this TNF in an in vivo model is difficult because of rapid equilibration of this cytokine into all compartments. A novel experimental design was devised to aid in accurate localization of the site of TNF release following a orthotopic liver transplant (OLT). In the first group (anhepatic), livers were removed from rats and splanchnic and systemic venous returns were then reestablished using a conduit of donor IVC and portal vein with a portasystemic shunt. In the second group (asplanchnic), the liver, stomach, pancreas, and intestine of the recipient were removed and a donor liver was reimplanted using the recipient IVC as the source of portal blood. The third (OLT-16) and fourth (OLT 8) groups underwent standard OLT with preservation times of 16 and 8 hr in 4 degrees C Euro-Collins solution, respectively. TNF levels were significantly increased in the OLT-16 group compared with the OLT-8 group. There were modest elevations of TNF in the anhepatic model, but the TNF in the asplanchnic model approached baseline. Absence of TNF in the asplanchnic group and a rise in TNF levels in the anhepatic group to that not significantly different from OLT-16 or OLT-8 suggest that a major source of TNF following preservation reperfusion may be the intestine.

Role of ischemic preconditioning and the portosystemic shunt in the prevention of liver and lung damage after rat liver transplantation1

“…It has been suggested that splanchnic congestion during liver transplantation leads to deleterious effects on hepatic and pulmonary integrity (3)(4)(5)(6). We evaluated whether a portosystemic shunt could avoid these undesirable effects.…”

“…The plasma TNF levels in all groups of the present study were reflected in the pulmonary damage evaluated by the accumulation of neutrophils, oxidative stress, and histologic findings, indicating the potential association between plasma TNF levels and lung damage. It has been suggested that the intestine and spleen may be an important source of TNF during liver transplantation as a consequence of splanchnic congestion (3,5,6,40). Along this line, studies have reported an increase in TNF levels after rat liver transplantation, whereas no increase in plasma TNF was detected in recipient rats, in which intestine was resected, or in splanchnic rats (5).…”

“…During hepatic reperfusion in the recipient, it seems that the release into the systemic circulation of proinflammatory substances from the intestine and spleen, resulting from splanchnic congestion, induces liver and lung damage (3)(4)(5)(6). Conversely, other authors have suggested that the graft by itself is the main source of proinflammatory mediators potentially responsible for the deleterious effects on the hepatocytes and the damaging effects on pulmonary integrity observed after hepatic I/R (7,8).…”

Endotoxins and Cytokines During Liver Transplantation: Changes in Plasma Levels and Effects on Clinical Outcome

“…8 Many factors may influence perioperative cytokine levels in recipients of liver grafts. Examples are the presence of endotoxin, 23,24 donor cytokine levels, 11,25 and manipu- lation 10 or ischemia of the bowel. 26 In animal experiments, cytokines have been shown to have a key role in postoperative graft function and rejection.…”

“…[6][7][8] Several factors may influence levels of cytokines, such as the presence of endotoxins during the liver transplantation procedure, 9 ischemia, and manipulation of other organs during transplantation, especially the splanchnic viscera. 10 Postreperfusion systemic levels of cytokines in the transplant recipient may be influenced by their serum levels in the donor. 11 Finally, preoperative systemic levels of cytokines in the transplant recipient might be an important factor because they are related to the nature and stage of the underlying disease.…”