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Published on: March 6, 2021
Review: Ischemia Reperfusion Injury-A Translational Perspective in Organ Transplantation
André Renaldo Fernández1,2, Rodrigo Sánchez-Tarjuelo3,4, Paolo Cravedi5
1Research Institute-IDIVAL, 39011 Santander, Spain.
Abstract:
Thanks to the development of new, more potent and selective immunosuppressive drugs together with advances in surgical techniques, organ transplantation has emerged from an experimental surgery over fifty years ago to being the treatment of choice for many end-stage organ diseases, with over 139,000 organ transplants performed worldwide in 2019. Inherent to the transplantation procedure is the fact that the donor organ is subjected to blood flow cessation and ischemia during harvesting, which is followed by preservation and reperfusion of the organ once transplanted into the recipient. Consequently, ischemia/reperfusion induces a significant injury to the graft with activation of the immune response in the recipient and deleterious effect on the graft. The purpose of this review is to discuss and shed new light on the pathways involved in ischemia/reperfusion injury (IRI) that act at different stages during the donation process, surgery, and immediate post-transplant period. Here, we present strategies that combine various treatments targeted at different mechanistic pathways during several time points to prevent graft loss secondary to the inflammation caused by IRI.
Insights
Organ transplantation is a life-saving treatment, but ischemia/reperfusion injury (IRI) can damage the organ. This review explores IRI pathways and strategies to prevent graft loss by targeting inflammation.
Area of Science:
- Transplantation immunology
- Surgical innovation
- Organ preservation
Background:
- Organ transplantation has advanced significantly, becoming a primary treatment for end-stage organ diseases.
- Ischemia/reperfusion injury (IRI) is an unavoidable complication during organ transplantation, impacting graft survival.
- IRI involves immune activation and inflammation, negatively affecting the transplanted organ.
Purpose of the Study:
- To review the mechanistic pathways of ischemia/reperfusion injury (IRI) in organ transplantation.
- To explore IRI's impact at various stages: donation, surgery, and post-transplant.
- To present multi-targeted therapeutic strategies to mitigate IRI-induced inflammation and prevent graft loss.
Main Methods:
- Literature review of existing research on IRI mechanisms.
- Analysis of therapeutic interventions targeting different IRI pathways.
- Discussion of strategies combining treatments at multiple time points.
Main Results:
- IRI involves complex pathways activated during organ harvesting, preservation, and reperfusion.
- Inflammation is a key driver of graft damage following IRI.
- Multi-faceted therapeutic approaches are necessary to effectively combat IRI.
Conclusions:
- Understanding IRI pathways is crucial for improving transplant outcomes.
- Targeting inflammation at various stages can prevent graft loss.
- Combined therapeutic strategies offer a promising approach to minimize IRI complications.

