{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:17:24Z","timestamp":1787861844729,"version":"build-2784847793"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Surg."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ischemia\u2013reperfusion (I\/R) injury remains a principal biological determinant of partial or total flap failure in reconstructive microsurgery. Reperfusion paradoxically initiates a coordinated cascade involving reactive oxygen species generation, lipid peroxidation, neutrophil activation, endothelial dysfunction, and microvascular obstruction, ultimately propagating progressive tissue necrosis. Despite extensive experimental investigation, effective translation into perioperative free flap salvage strategies remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A structured translational synthesis was conducted integrating institutional experimental flap I\/R studies performed over two decades with systematically mapped external literature published between 2000 and February 2026. Study identification followed PRISMA-informed search principles to ensure methodological transparency. Data extraction adhered to ARRIVE 2.0 domains to standardize experimental quality assessment. Given predefined biological heterogeneity in flap type, ischemia duration, intervention timing, and outcome definitions, quantitative meta-analysis was not pursued. Instead, biologically stratified comparative analyses were performed, and biologically contextualized viability changes were descriptively evaluated within comparable severe ischemia subgroups to preserve mechanistic interpretability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Across experimental platforms, effective interventions demonstrated a reproducible biological signature characterized by attenuation of lipid peroxidation, suppression of neutrophil-mediated inflammation, restoration of endogenous antioxidant defenses, and preservation of nitric oxide bioavailability. In a comparable severe ischemia epigastric island flap paradigm, trimetazidine, propionyl-L-carnitine, and lutein each demonstrated improved survival area relative to ischemic controls within their respective experimental contexts. Surgical conditioning strategies exhibited robust protection, with venous flap pre-arterialization and delay procedures achieving survival rates approaching near-complete viability in the respective model. However, these conditioning strategies are not directly transferable to acute free flap salvage scenarios and are primarily applicable to planned or staged reconstructive settings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Flap I\/R injury follows a reproducible oxidative stress\u2013inflammation\u2013microvascular dysfunction axis. Interventions targeting multiple components of this cascade appear to demonstrate a more reproducible protective pattern across severe ischemia conditions within their respective experimental contexts. These findings establish a translational mechanistic framework to guide rational adjunctive strategies in high-risk free flap protocols and support prospective clinical integration in microsurgical salvage scenarios. This synthesis is intended to guide mechanistic prioritization rather than imply direct interventional equivalence across models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fsurg.2026.1824889","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T05:24:38Z","timestamp":1776662678000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A translational mechanistic synthesis of ischemia\u2013reperfusion injury in experimental flap models toward free flap salvage"],"prefix":"10.3389","volume":"13","author":[{"given":"Ovunc","family":"Akdemir","sequence":"first","affiliation":[{"name":"Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, Istanbul Ayd\u0131n University","place":["Istanbul, 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