Current Evidence of Minimizing Ischemia-Reperfusion Injury in a Rat Flap Model: A Systematic Review

To reduce the risk of ischemia-reperfusion injury following free tissue transfer, many treatments focus on the upregulation of the antioxidant and anti-inflammatory responses to promote reversible cell injury by reducing oxygen free radicals, mitochondrial damage, neutrophil-mediated inflammation, and complement activation. This review aims to characterize interventions in rats for reducing flap necrosis as a result of ischemia-reperfusion injury.

Following the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of the PubMed, Embase, Web of Science, Scopus, and OVID repositories was conducted from inception to July 2025. The inclusion criteria consisted of any study focusing on minimizing ischemia-reperfusion injury in rat flap models.

Of the 2448 unique citations, 72 (n = 3423 rats) were included. Interventions included pharmacological therapies (n = 54/72, 75%), followed by surgical (n = 12/72, 16.7%), hyperbaric oxygen (n = 4/72, 5.6%), biological (n = 3/72, 4.2%), temperature (n = 1/72, 1.4%), and perfusion (n = 1/72, 1.4%) therapies. The overall success rate of interventions for minimizing ischemia-reperfusion injury was 97.2% (n = 70/72). Of the 56 unique interventions identified, further research involving large animal models was conducted in 9/56 (16.1%), whereas human involvement was reported in 6/56 (10.7%).

Interventions demonstrated a high reported rate of success for reducing ischemia-reperfusion injury (97.2%). However, only 10.7% of interventions were found to be further studied among human patients, highlighting the need for additional research to reduce ischemia-reperfusion injury without significant disruptions to the perioperative workflow. Identification of the patient population that would benefit most from prophylactic interventions is also needed.