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5251253 
Journal Article 
Effects of organ preservation, ischemia time and caspase inhibition on apoptosis and microcirculation in rat pancreas transplantation 
Drognitz, O; Obermaier, R; Liu, X; Neeff, H; Von Dobschuetz, E; Hopt, UT; Benz, S 
2004 
Yes 
American Journal of Transplantation
ISSN: 1600-6135
EISSN: 1600-6143 
4 
7 
1042-1050 
English 
This study was undertaken to examine the impact of ischemia-reperfusion (I/R) injury on microcirculation and apoptosis in experimental pancreas transplantation. Pancreatic grafts were subjected to different preservation solutions and cold ischemia times (CITs): University of Wisconsin (UW), 6-h CITs (group U6); UW, 18-h CITs (group U18); normal saline, 6-h CITs (group S6); and normal saline, 6-h CITs with Z-Asp-2,6-dichlorobenzoyloxymethylketone (pan-caspase inhibitor; group S6 & CI). Nontransplanted animals served as controls. At 1- and 2-h reperfusion microcirculation was assessed by means of intravital microscopy. Apoptosis was detected by in situ nick end-labeling method (TUNEL) at 2-h reperfusion. Deterioration of microcirculation was lowest in group U6 and highest in groups S6 and S6 & CI compared with controls. The apoptotic index (cells per high power fields) of groups U6, U18 and S6 correlated well with functional capillary density (r=- 0,70, p < 0.0001) and leucocyte sticking (r= 0,69, p < 0.0001) at 1-h reperfusion. Caspase inhibition had no impact on microcirculation but significantly reduced AI compared with group S6 (p < 0.001). These data suggest that pancreatic I/R injury-induced apoptotic cell death well predicts the extent of [corrected] microcirculatory impairment. Caspase inhibition might be a promising strategy in reducing I/R injury in pancreas transplantation. 
Animals; Apoptosis; Aspartic Acid/analogs & derivatives/pharmacology; Capillaries/metabolism; Caspase Inhibitors; DNA Fragmentation; Endothelium, Vascular/metabolism; Enzyme Inhibitors/pharmacology; In Situ Nick-End Labeling; Ischemia; Leukocytes/metabolism; Microcirculation; Organ Preservation/methods; Pancreas/cytology/metabolism; Pancreas Transplantation/methods; Protease Inhibitors/pharmacology; Rats, Inbred Lew; Reperfusion Injury; Time Factors