title: Pretreatment Combination Reduces Remote Organ Damage Secondary to Intestinal Reperfusion Injury in Mice: Follow-up Study.
abstract: BACKGROUND
  Intestinal ischemia-reperfusion injury occurs after different surgical treatments, including intestinal transplantation. This harmful process may have an effect in remote organs, leading to multiple organ dysfunction syndrome and death. Therefore, to establish strategies to attenuate local and remote damage constitutes a challenge for experimental and clinical surgeons in the intestinal surgical field.
  
  
  METHODS
  We evaluated the effect of ischemic preconditioning and tacrolimus pretreatment applied alone and in combination against local and remote damage caused by prolonged intestinal ischemia-reperfusion injury in a mouse model of warm ischemia.
  
  
  RESULTS
  Ischemic preconditioning applied alone and in combination with tacrolimus decreased histological damage (P < .05), number of apoptotic cells (P < .05), nitrosative stress (P < .01), and serum lactate dehydrogenase activity (P < .05) and lowered uremia (P < .05) compared with untreated post-reperfused intestines. Regarding remote organ damage, combination therapy was the unique condition able to attenuate lung (mainly neutrophil infiltration and hemorrhage), liver (sinusoidal congestion and hepatic vacuolization), and kidney (acute tubular necrosis and hydropic degeneration) histological alterations (P < .05), compared with the untreated group.
  
  
  CONCLUSIONS
  These results support the application of these strategies in combination to minimize the impact of ischemia-reperfusion injury in the whole organism as a strategy to prevent multiple organ dysfunction syndromes and minimize the clinical impact.
authors.affiliation: Instituto de Trasplante Multiorgánico (ITMO), Fundación Favaloro, Buenos Aires, Argentina; Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP) UNLP-CONICET, La Plata, Argentina; Laboratorio de Trasplante de Organos y Tejidos (LTO), Facultad de Ciencias Médicas, UNLP, La Plata, Argentina. Electronic address: pablo_stringa@hotmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Stringa
authors.affiliation: Laboratorio de Trasplante de Organos y Tejidos (LTO), Facultad de Ciencias Médicas, UNLP, La Plata, Argentina.
authors.forename: N
authors.initials: N
authors.lastname: Lausada
authors.affiliation: Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP) UNLP-CONICET, La Plata, Argentina.
authors.forename: D
authors.initials: D
authors.lastname: Romanin
authors.affiliation: Laboratorio de Análisis de Imágenes, Facultad de Ciencias Veterinarias, UNLP, La Plata, Argentina.
authors.forename: E
authors.initials: E
authors.lastname: Portiansky
authors.affiliation: Laboratorio de Análisis de Imágenes, Facultad de Ciencias Veterinarias, UNLP, La Plata, Argentina.
authors.forename: C
authors.initials: C
authors.lastname: Zanuzzi
authors.affiliation: Laboratorio de Patología Especial Veterinaria, Facultad de Ciencias Veterinarias, UNLP, La Plata, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Machuca
authors.affiliation: Instituto de Trasplante Multiorgánico (ITMO), Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Gondolesi
authors.affiliation: Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP) UNLP-CONICET, La Plata, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Rumbo
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007422:Intestines / Q000098:blood supply* / Q000637:transplantation; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney; D008099:Liver; D008168:Lung; D008297:Male; D051379:Mice; D009102:Multiple Organ Failure / Q000517:prevention & control*; D015427:Reperfusion Injury / Q000150:complications / Q000517:prevention & control*; D016559:Tacrolimus / Q000008:administration & dosage*; D052096:Warm Ischemia / Q000009:adverse effects
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus