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Updated: Mar 25, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Pretreatment Combination Reduces Remote Organ Damage Secondary to Intestinal Reperfusion Injury in Mice: Follow-up
P Stringa1, N Lausada2, D Romanin3
1Instituto 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.
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.
Insights
Combining ischemic preconditioning and tacrolimus pretreatment effectively reduces intestinal ischemia-reperfusion injury and protects remote organs from damage. This combined therapy is crucial for preventing multiple organ dysfunction syndrome.
Area of Science:
- Surgical Research
- Transplantation Immunology
- Organ Injury Mechanisms
Background:
- Intestinal ischemia-reperfusion (I/R) injury is a critical complication in intestinal surgery and transplantation.
- This injury can lead to systemic effects, including remote organ damage and multiple organ dysfunction syndrome (MODS).
- Developing strategies to mitigate both local and systemic damage from I/R injury is a significant clinical challenge.
Purpose of the Study:
- To investigate the protective effects of ischemic preconditioning (IP) and tacrolimus pretreatment, alone and in combination.
- To evaluate their efficacy against local intestinal damage and remote organ injury following prolonged warm ischemia-reperfusion in a mouse model.
Main Methods:
- A mouse model of prolonged warm intestinal ischemia-reperfusion was established.
- Animals were treated with IP, tacrolimus, or a combination of both, compared to an untreated control group.
- Histological analysis, apoptotic cell counts, nitrosative stress markers, serum lactate dehydrogenase, and uremia levels were assessed.
Main Results:
- Both IP and combination therapy significantly reduced intestinal histological damage, apoptosis, nitrosative stress, and serum lactate dehydrogenase.
- Combination therapy uniquely attenuated histological damage in remote organs, including the lungs, liver, and kidneys.
- Specific improvements included reduced neutrophil infiltration in lungs, congestion in the liver, and tubular necrosis in kidneys.
Conclusions:
- Combined IP and tacrolimus pretreatment offers significant protection against local intestinal I/R injury.
- This combination therapy is effective in preventing multi-organ damage, highlighting its potential for preventing MODS.
- These findings support the clinical application of combined strategies to minimize the systemic impact of I/R injury.
