Effects of organ preservation, ischemia time and caspase inhibition on apoptosis and microcirculation in rat pancreas transplantation.
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.
Drognitz
Oliver
O
Department of General and Digestive Surgery, University of Freiburg, Freiburg, Germany. oliverdrognitz@web.de
Obermaier
Robert
R
Liu
Xuemei
X
Neeff
Hannes
H
von Dobschuetz
Ernst
E
Hopt
Ulrich T
UT
Benz
Stefan
S
D000818:Animals; D017209:Apoptosis; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002196:Capillaries / Q000378:metabolism; D061945:Caspase Inhibitors; D053938:DNA Fragmentation; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007511:Ischemia; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D009926:Organ Preservation / Q000379:methods*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D016035:Pancreas Transplantation / Q000379:methods*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury; D013997:Time Factors
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D011480:Protease Inhibitors; C093260:benzyloxycarbonyl-Asp-CH2OC(O)-2,6-dichlorobenzene; D001224:Aspartic Acid