2011 - ISBTS 2011 Symposium
Oral Communications 2: Ischemia / Reperfusion
4.113 - Effect of ischemic preconditioning, and tacrolimus pre-treatment as strategies to attenuate intestinal ischemia-reperfusion injury in a mouse model
Presenter: Pablo, Stringa, Buenos Aires, Argentina
Authors: Pablo Stringa1, Natalia Lausada1, Mariana Machuca3, David Romanin2, Ana Cabanne4, Martín Rumbo2, Gabriel Gondolesi1
Effect of ischemic preconditioning, and tacrolimus pre-treatment as strategies to attenuate intestinal ischemia-reperfusion injury in a mouse model
Pablo Stringa1, Natalia Lausada1, Mariana Machuca3, David Romanin2, Ana Cabanne4, Martín Rumbo2, Gabriel Gondolesi1
1Instituto de Trasplante Multiorganico - Programa de Inmunobiología e Investigación Traslacional en Trasplante, Hospital Universitario - Fundación Favaloro, Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina; 2Laboratorio de Investigaciones del Sistema Inmune, Facultad de Ciencias Exactas Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina; 3Departamento de Patologia Especial, Facultad de Ciencias Veterinaris Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina; 4Anatomia Patologica, Hospital Universitario - Fundación Favaloro, Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Background: Among the organs, intestine is probably the most sensitive to ischemia reperfusion injury (IRI), independently of the cause. Intestinal IRI may alter the integrity of the mucosal enteric barrier, causing bacterial translocation, sepsis and triggering a systemic inflammatory response syndrome leading to multi organ failure and death. Different degrees of IRI occurred after intestinal transplantation, therefore to establish strategies to mitigate IRI is a major objective for basic and translational research in the field of today’s intestinal surgery. The aim of the present study was to evaluate the effect of ischemic preconditioning (IPC) and pre-treatment with tacrolimus (TC) in intestinal damage after immediate reperfusion.
Material and Methods: 36 adult male Balb/c mice weighing 30 ± 3 grams were divided in 4 groups with 9 mice each: Group C, (n=9) 40 min occlusion of superior mesenteric artery (OSMA) was applied follow by reperfusion without treatment; Group TC: was pre-treated with intragastric administration of TC 3mg/kg 12 hs before OSMA. Group IPC: a cycle of ten minutes of intestinal ischemia 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 from five animals in each group. Histological damage was evaluated using Park´s score. The remaining animals 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 C 4.2 ± 0,8 (p<0.001). All animals from SH and IPC survived 24 hs . In TC, 1 mice died between 18 and 24 hs and 3 were able to survive 24 hs after surgery. All C mice died before 24 hs. Significant differences 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 and improve survival rate. To combine both treatments and to reproduce it in the intestinal transplantation model in mice are our next research objectives.
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