Effect of ischemic preconditioning, and tacrolimus pre-treatment as strategies to attenuate intestinal ischemia-reperfusion injury in a mouse model.

PABLO STRINGA; NATALIA LAUSADA; MACHUCA MARIANA; ROMANIN, DAVID (1);; CABANNE, ANA; MARTIN RUMBO; GABRIEL GONDOLES

Congreso; XII International Small Bowel Transplantation Symposium; 2011

background: among the organs, intestine is probably the most sensitive to ischemia reperfusioninjury (IrI), independently of the cause. Intestinal IrI may alter the integrity of the mucosal entericbarrier, causing bacterial translocation, sepsis and triggering a systemic inflammatory responsesyndrome leading to multi organ failure and death. Different degrees of IrI occurred after intestinaltransplantation, therefore to establish strategies to mitigate IrI is a major objective for basic andtranslational research in the field of today’s intestinal surgery. the aim of the present study was toevaluate the effect of ischemic preconditioning (IPC) and pre-treatment with tacrolimus (tC) inintestinal damage after immediate reperfusion.Material and Methods: 36 adult male balb/c mice weighing 30 ± 3 grams were divided in 4groups with 9 mice each: group C, (n=9) 40 min occlusion of superior mesenteric artery (oSMa) wasapplied follow by reperfusion without treatment; group tC: was pre-treated with intragastricadministration of tC 3mg/kg 12 hs before oSMa. group IPC: a cycle of ten minutes of intestinalischemia followed by ten minutes of reperfusion was performed before oaMS. finally a Sham group(SH) was included. thirty minutes post reperfusion; samples of distal jejunum were obtained fromfive animals in each group. Histological damage was evaluated using Park´s score. the remaininganimals were followed for 24 hours to analyze survival.results: SH group showed normal Jejunum. Park’s value for IPC was 2.2 ± 0.8, tC 2.8 ± 0.4 and C4.2 ± 0,8 (p<0.001). all animals from SH and IPC survived 24 hs. In tC, 1 mice died between 18 and24 hs and 3 were able to survive 24 hs after surgery. all C mice died before 24 hs. Significantdifferences in IrI and survival were observed between IPC and tC Vs C (log-rank: p<0.002).conclusions: both strategies attenuate histological damage after immediately reperfusion andimprove survival rate. to combine both treatments and to reproduce it in the intestinaltransplantation model in mice are our next research objectives.