title: Xenogeneic rejection mechanisms shown by intravital microscopy.
abstract: The importance of this model is that it showed exactly where in the organ the xenogeneic damage occurred. The liver received the blood mainly via portal veins, which merge with the pulsatile arterioles in the Disse spaces. This periportal area is followed by the sinusoids and ends in the central or postsinusoidal vein. IVM enables us to differentiate between perfused and unperfused sinusoids and to calculate the ratio. Not all sinusoids are perfused at any time. It appears that 5% to 10% are unperfused. During xenoperfusion, only 65% of sinusoids show blood flow after a perfusion of 12 minutes. This is less than in hemorrhagic shock. Only the combined platelet inhibitors and apheresis resulted in remarkable improvement. The calculation of an index indicates the improvement of acinar perfusion. Thrombocytes and leukocytes remain, however, in the liver. In conclusion, the model used to analyze the dynamics of microvascular liver perfusion and sinusoidal perfusion is suitable for such investigations in a xenogeneic model. It has no major side effects, either on the perfusing blood or on the liver, as proved in the isogeneic control group. The important finding in our eyes is that the perfusion failure begins in the periportal fields, where the blood enters the foreign microvasculature and where the leukocytes first come in contact with the foreign endothelium. All previous manipulations had only a minor impact on this contact of cells with the foreign endothelium. The study indicates that the early events of xenogeneic hyperacute rejection are of unspecific character and involve leukocytes and thrombocytes to a major degree, thus being responsible for the dramatic decrease in the microcirculation in xenogeneic livers.
authors.affiliation: Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximillians University, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Hammer
authors.forename: R
authors.initials: R
authors.lastname: Linke
authors.forename: D
authors.initials: D
authors.lastname: Seehofer
authors.forename: M
authors.initials: M
authors.lastname: Diefenbeck
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001646:Bile / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001803:Blood Transfusion; D004546:Elapid Venoms / Q000494:pharmacology; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D008856:Microscopy, Fluorescence / Q000379:methods; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous / Q000473:pathology / Q000502:physiology*; D014185:Transplantation, Isogeneic; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001381:Azepines; D004546:Elapid Venoms; D010972:Platelet Activating Factor; D014230:Triazoles; C016310:cobra venom factor; C063964:bepafant