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Effects of Organ Preservation, Ischemia Time and Caspase Inhibition on Apoptosis and Microcirculation in Rat Pancreas Transplantation
Author(s) -
Drognitz Oliver,
Obermaier Robert,
Liu Xuemei,
Neeff Hannes,
Dobschuetz Ernst von,
Hopt Ulrich T.,
Benz Stefan
Publication year - 2004
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2004.00457.x
Subject(s) - microcirculation , medicine , transplantation , apoptosis , ischemia , pancreas transplantation , tunel assay , reperfusion injury , viaspan , pancreas , intravital microscopy , pathology , endocrinology , andrology , immunohistochemistry , biology , biochemistry , kidney 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 microcirculatory impairment. Caspase inhibition might be a promising strategy in reducing I/R injury in pancreas transplantation.