Donor pretreatment with gadolinium chloride improves early graft function and survival after porcine liver transplantation.
Kupffer cell depletion by gadolinium chloride (GdCl(3)) in rat livers has previously been proven to minimize hepatic ischemia/reperfusion injury after experimental liver transplantation (LTX). In the current study, we evaluated the effects of donor pretreatment with GdCl(3) on hepatic ischemia/reperfusion injury, macro- and microcirculation, and endotoxin clearance of the liver in a porcine model of experimental LTX. Two groups of 12 pigs were treated either with intravenous NaCl (0.9%; control) or GdCl(3) (20 mg/kg). Twenty-four hours after pretreatment, hepatic macrocirculation was quantified by Doppler flowmetry and liver parenchymous microcirculation by implanted thermodiffusion electrodes. The liver grafts were transplanted after 4-6 h of cold ischemia in University of Wisconsin (UW) solution. At 1 and 24 h after LTX, the perfusion values were re-evaluated and histology, biochemical (aspartate aminotransferase, AST) and functional parameters (partial thromboplastin time, prothrombin time, and bilirubin) were analyzed. Furthermore, endotoxin clearance of the liver was evaluated at all time points. In GdCl(3)-treated animals 80% of the Kupffer cells were destroyed, and 24 h after LTX ischemia/reperfusion injury in treated grafts was significantly lower in comparison to controls, as shown by histology, AST levels (741+/-490 U/l in controls vs 379+/-159 U/l in treated grafts, P<0.05), survival (67% vs 92%), and enhanced macro- (total transhepatic blood flow [THBF]=112+/-22 ml/min per 100 g in controls vs 157+/-45 ml/min per 100 g in treated grafts, P<or=0.05) and microcirculation (thermodiffusion [TD]=73+/-9 ml/min per 100 g in controls vs 90+/-16 ml/min per 100 g in treated grafts, P<or=0.05). Despite destruction of the macrophage system in the liver, the transhepatic endotoxin gradient of treated livers was enhanced before and 1 h after transplantation (58% in controls vs 85% in treated grafts, P<0.05). Destruction of Kupffer cells of donors by pretreatment with GdCl(3) in pigs is effective in preventing liver graft dys- and nonfunction after LTX. Pretreatment with GdCl(3) does not diminish but increase hepatic endotoxin clearance.
von Frankenberg
Moritz
M
Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. moritz_von_frankenberg@med.uni-heidelberg.de
Golling
Markus
M
Mehrabi
Arianeb
A
Nentwich
Hagen
H
Klar
Ernst
E
Kraus
Thomas W
TW
D000818:Animals; D002452:Cell Count; D004731:Endotoxins / Q000097:blood; D005682:Gadolinium / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects*; D007728:Kupffer Cells / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000503:physiopathology*; D008102:Liver Circulation / Q000187:drug effects; D016031:Liver Transplantation; D008833:Microcirculation / Q000187:drug effects; D011168:Portal System / Q000187:drug effects / Q000503:physiopathology; D011300:Preoperative Care; D015996:Survival Rate; D013552:Swine; D014019:Tissue Donors
D004731:Endotoxins; D005682:Gadolinium; C038958:gadolinium chloride