Microvascular Derangement in Liver Transplantation
Michael D. Menger
Microcirculatory derangements in organ transplantation, characterized by capillary perfusion failure and inflammation-associated leukocyte recruit- ment, are major determinants of the manifestation of graft dysfunction and destruction. Although preservation/cold storage, post-transplant reperfusion, and rejection have to be considered as individual factors contributing to injury, recent studies have indicated that ischemia/reperfusion-associated events may trigger immune-response-mediated late rejection. There is major evidence that the microcirculatory derangements induced by cold preserva- tion and reperfusion involve oxygen radicals, complement, phospholipase A2, leukotrienes, thromboxane, platelet-activating factor and endothelin-1, as well as the activation and functioning of leukocytic and endothelial selectins, b2- integrins, and ICAM-1. This view is based on the fact that blockade or neu- tralization of these inflammatory mediators and adhesion molecules results in significant amelioration of microvascular graft dysfunction. Interestingly, the ischemia/reperfusion-associated apoptotic cell death additionally con- tributes to the manifestation of microcirculatory derangements, because inhibition of apoptosis by blockade of p53 results in amelioration of micro- circulation dysfunction. The introduction of novel techniques for the study of human microcirculation, such as thermodiffusion and orthogonal polariza- tion spectral imaging, may in future assist in improving both early diagnosis of microcirculatory derangements and in the monitoring of the appropriate- ness of therapy in clinical transplantation surgery.
145 Institute for Clinical and Experimental Surgery, University of Saarland, D-66421 Homburg/Saar, Germany
