Mucosal villus microcirculatory disturbances associated with rat intestinal ischaemia-reperfusion injury are not prevented by tacrolimus.
OBJECTIVE
Microcirculatory disturbances following small intestinal ischaemia-reperfusion (I/R) injury lead to tissue damage that may affect short- and long-term outcome after transplantation. The immunosuppressive drug Tacrolimus (FK506) attenuates I/R injury in a number of organs, raising the possibility that it might be able to control both I/R injury and rejection after small bowel transplantation. However, its effects on intestinal I/R injury have not been evaluated.


METHODS
PVG rats were subjected to 30 min intestinal ischaemia. Animals received Tacrolimus (1 mg/kg i.p.) 4 and 1 h prior to ischaemia. The mucosa was visualised in an exteriorised ileal segment using in vivo microscopy. FITC-BSA or Acridine orange was used to quantitate macromolecular leak (MML) and leucocyte adhesion respectively every 15 min for 2 h during reperfusion. Heart rate and mean blood pressure (mBP) were monitored throughout the experiment.


RESULTS
Ten of 12 untreated animals subjected to intestinal I/R injury failed to survive the 2-hour reperfusion period. MML and leucocyte adhesion were increased in untreated animals (p < 0.001) and blood flow stasis eventually ensued. Similar results were obtained for Tacrolimus pre-treated I/R animals, with 10 of 12 animals again failing to survive reperfusion.


CONCLUSIONS
Despite previous evidence that Tacrolimus reduces I/R injury in other organs, it did not improve survival rates or prevent villus microcirculatory disturbances following intestinal I/R injury. The severity of microcirculatory damage suffered by the small intestine highlights the importance of alternative therapies to combat I/R in this organ.
Kalia
Neena
N
Department of Biomedical Science, Alfred Denny Building, Western Bank, University of Sheffield, Sheffield, UK. n.kalia@sheffield.ac.uk
Wood
Richard F M
RF
Pockley
A Graham
AG
Brown
Nicola J
NJ
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000503:physiopathology; D008853:Microscopy; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D013152:Splanchnic Circulation / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D016559:Tacrolimus