{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:29:15Z","timestamp":1770748155624,"version":"3.49.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"9-10","license":[{"start":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T00:00:00Z","timestamp":1667001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Vascularized composite allotransplantation (VCA) is a restorative surgical procedure to treat whole or partially disfiguring craniofacial or limb injuries. The routine clinical use of this VCA surgery is limited using compromised allografts from deceased donors and by the failure of the current hypothermic preservation protocols to extend the allograft\u2019s cold ischemia time beyond 4\u2009h. We hypothesized that the active replenishment of the cellular cytosolic adenosine-5`-triphosphate (ATP) stores by means of energy delivery vehicles (ATPv) encapsulating high-energy ATP is a better strategy to improve allograft\u2019s tolerance to extended cold ischemia times.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>We utilized established rat model of isolated bilateral in-situ non-cycled perfusions of both hind limbs. Ipsilateral and contralateral limbs in the anesthetized animal were randomized for simultaneous perfusions with either the University of Wisconsin (UW) solution, with\/without O2 supplementation (control), or with the UW solution supplemented with the ATPv, with\/without O2 supplementation (experimental). Following perfusion, the hind limbs were surgically removed and stored at 4\u00b0C for 12, 16, or 24\u2009hours as extended cold ischemia times. At the end of each respective storage time, samples of skin, and soleus, extensor digitalis longus, and tibialis anterior muscles were recovered for assessment using tissue histology and tissue lysate studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Control muscle sections showed remarkable microvascular and muscle damage associated with loss of myocyte transverse striation and marked decrease in myocyte nucleus density. A total of 1,496 nuclei were counted in 179 sections of UW-perfused control muscles in contrast to 1,783 counted in 130 sections of paired experimental muscles perfused with the ATPv-enhanced perfusate. This yielded 8 and 13 nuclei\/field for the control and experimental muscles, respectively (P\u2009&amp;lt;\u2009.004). Oxygenation of the perfusion solutions before use did not improve the nucleus density of either the control or experimental muscles (n\u2009=\u20097 animals, P\u2009&amp;gt;\u2009.05). Total protein isolated from the muscle lysates was similar in magnitude regardless of muscle type, perfusion protocol, or duration of cold ischemia time. Prolonged static cold preservation of the hind limbs completely degraded the composite tissue\u2019s Ribonucleic acid (RNA). This supplementary result confirms the notion that that reverse transcription\u2013Polymerase Chain Reaction, enzyme-linked immunosorbent assay, or the respiratory complex II enzyme activity techniques should not be used as indices of graft quality after prolonged static cold storage.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In conclusion, this study demonstrates that active cellular cytosolic ATP replenishment increases hind limb composite tissue tolerance to extended cold ischemia times. Quality indicators and clinically relevant biomarkers that define composite tissue viability and function during static cold storage are warranted.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/milmed\/usac331","type":"journal-article","created":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T11:48:36Z","timestamp":1667044116000},"page":"2960-2968","source":"Crossref","is-referenced-by-count":1,"title":["Cellular Cytosolic Energy Replenishment Increases Vascularized Composite Tissue Tolerance to Extended Cold Ischemia Time"],"prefix":"10.1093","volume":"188","author":[{"given":"El Rasheid","family":"Zakaria","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, College of Medicine, The University of Arizona , Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wali","family":"Yousufzai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Texas Tech University Health Sciences Center , Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Obaid","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, College of Medicine, The University of Arizona , Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samer","family":"Asmar","sequence":"additional","affiliation":[{"name":"Department of Surgery, Staten Island University Hospital , Staten Island, NY 10305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiu-Hsieh","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, College of Medicine, The University of Arizona , Tucson, AZ 85724, USA"},{"name":"The Mel and Enid Zuckerman College of Public, The University of Arizona , Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bellal","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, College of Medicine, The University of Arizona , Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,10,29]]},"reference":[{"issue":"3","key":"2023083018175073700_R1","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s40472-014-0025-6","article-title":"Vascularized composite allografts: procurement, allocation, and implementation","volume":"1","author":"Rahmel","year":"2014","journal-title":"Curr Transplant Rep"},{"issue":"3","key":"2023083018175073700_R2","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1111\/ctr.12117","article-title":"Vascularized composite tissue allotransplantation\u2014state of the 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