Ischemic preconditioning of small bowel mitigates the late phase of reperfusion injury: heme oxygenase mediates cytoprotection.
BACKGROUND
Ischemia and reperfusion (IR) injury of the intestine is a major cause of morbidity and mortality following small bowel transplantation. The current study evaluates the effect of ischemic preconditioning (IPC) on the intestinal microcirculation in the late phase of IR injury of the intestine.


METHODS
Sixty rats were randomly allocated to 5 study groups (n = 12 per group): (1) sham, (2) IR (3) IPC, (4) pyrrolidine dithiocarbamate (PDTC) (HO-1 inducer), and (5) zinc protoporhyrin (ZnPP) (HO-1 inhibitor). Mucosal perfusion and leukocyte-endothelial interactions were measured with the aid of an intravital microscope. At the end of the experiments, blood samples for lactate dehydrogenase (LDH) levels and biopsies of ileum for histologic evaluation were obtained.


RESULTS
IPC significantly improved the mucosal perfusion and decreased the leukocyte-endothelial interactions. Histologic examination showed that ileal mucosa was significantly less injured in the IPC and PDTC groups as compared with the IR group.


CONCLUSIONS
IPC protects the intestine from late reperfusion injury. HO-1 is involved in this protection. These findings may be of significant importance in clinical small bowel transplantation.
Gastrointestinal and Hepatobiliary Research Unit, UCL Division of Surgery and Interventional Science, Royal Free and University College Medical School, University College London, London, UK.
Ismail H
IH
Mallick
Marc C
MC
Winslet
Alexander M
AM
Seifalian
D000818:Animals; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007082:Ileum / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology / Q000637:transplantation; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D019194:Ischemic Preconditioning; D008297:Male; D008833:Microcirculation; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D012778:Short Bowel Syndrome / Q000601:surgery
D051547:Heme Oxygenase-1