A natural tetrahydropyrimidine protects small bowel from cold ischemia and subsequent warm in vitro reperfusion injury.
OBJECTIVE
Ischemia/reperfusion (I/R) injury is a major difficulty in small bowel transplantation. Many postoperative complications are caused by damage to the intestinal mucosa following organ retrieval and during cold storage. Here we investigate whether 1-, 4-, 5-, 6-tetrahydro-2-methyl-4-pyrimidine carboxylic acid (THP) can protect ileal mucosa and muscularis against cold ischemia and subsequent warm in vitro reperfusion injury.


METHODS
Small rat bowels were stored in the absence or presence of THP or its synthetic derivative lauryl-THP for 18 h at 4 degrees C. Several biochemical parameters were evaluated following isolated reperfusion in tissue grafts and/or effluent solution. Graft morphology was analyzed by electron microscopy. Ceramide was quantified as a potential target of THP action.


RESULTS
THP considerably inhibited apoptosis and improved all parameters illustrating membrane and subcellular integrity and functionality. Parallel studies with lauryl-THP failed to show a similar protective effect. Lauryl-THP, in contrast to THP, also failed to decrease tissue ceramide content, indicating the involvement of this well-known mediator of cellular stress response.


CONCLUSIONS
THP effectively protects ileal mucosa and muscularis against ischemia and reperfusion injury, indicating for the first time the clinical relevance of this new and promising molecule that might become a central component in tissue and organ protection in the near future.
Wei
Lai
L
House of Experimental Therapy, University of Bonn, Germany.
Wedeking
Annika
A
Buttner
Reinhard
R
Kalff
Jorg C
JC
Tolba
René H
RH
van Echten-Deckert
Gerhild
G
D000599:Amino Acids, Diamino / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism; D050377:Cold Ischemia; D006801:Humans; D007082:Ileum / Q000098:blood supply / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D007421:Intestine, Small / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries* / Q000637:transplantation; D007511:Ischemia / Q000188:drug therapy*; D008297:Male; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D052096:Warm Ischemia
D000599:Amino Acids, Diamino; D002518:Ceramides; C045628:ectoine