Development of a 24-h Preservation Protocol of Forearm Vascularized Composite Allotransplants in Nonhuman Primates Using Subnormothermic Machine Perfusion
Background. Subnormothermic machine perfusion shows promise as a viable alternative to static cold storage for prolonged preservation of vascularized composite allografts. To date, most studies have been conducted in nonprimate models, and we report its first utilization in a cynomolgus forearm prec...
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Wolters Kluwer
2025-09-01
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| Series: | Transplantation Direct |
| Online Access: | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001849 |
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| author | Haïzam Oubari, MD Loïc Van Dieren, MS Yanis Berkane, MD Lucile Cabanel, MD Mark A. Randolph, MAS Curtis L. Cetrulo, Jr, MD Alexandre G. Lellouch, MD Korkut Uygun, PhD |
| author_facet | Haïzam Oubari, MD Loïc Van Dieren, MS Yanis Berkane, MD Lucile Cabanel, MD Mark A. Randolph, MAS Curtis L. Cetrulo, Jr, MD Alexandre G. Lellouch, MD Korkut Uygun, PhD |
| author_sort | Haïzam Oubari, MD |
| collection | DOAJ |
| description | Background. Subnormothermic machine perfusion shows promise as a viable alternative to static cold storage for prolonged preservation of vascularized composite allografts. To date, most studies have been conducted in nonprimate models, and we report its first utilization in a cynomolgus forearm preclinical model for 24-h preservation.
Methods. Forearms were procured from nonhuman primates weighing between 5 and 8 kg. Two perfusion protocols were implemented. In group 1 (n = 6), limbs were perfused with 1.5 L of recirculating Steen; the perfusate flow was adjusted to maintain stable vascular pressures. In group 2 (n = 6), limbs were perfused with a Steen+ solution, doubling the albumin concentration, with a full-volume exchange at mid-perfusion under a stable low-flow regimen. Dynamic and metabolic parameters, histological analysis, and response to neurostimulation were assessed.
Results. After 24 h of continuous perfusion, mean weight gain was 24.8 ± 5.5% in group 1 and 8.0 ± 4.7% in group 2. Perfusion and metabolic parameters indicated the onset of a compartment syndrome in group 1 with an increase in resistance, lactate, and potassium production at mid-perfusion. In group 2, dynamic and metabolic parameters remained stable for 24 h, and histological analysis showed well-preserved tissues. Finally, in group 2, limbs exhibited muscular contraction recovery quantified at 2.4/5 ± 0.89 after 24 h compared with 0/5 after 3 h of ischemia or after perfusion in group 1.
Conclusions. Successful 24-h perfusion and muscle contractility restoration demonstrate promising outcomes for vascularized composite allograft preservation and reconditioning. |
| format | Article |
| id | doaj-art-c6de70225863444ab7fa8fca694d0739 |
| institution | Kabale University |
| issn | 2373-8731 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Transplantation Direct |
| spelling | doaj-art-c6de70225863444ab7fa8fca694d07392025-08-26T03:26:16ZengWolters KluwerTransplantation Direct2373-87312025-09-01119e184910.1097/TXD.0000000000001849202509000-00004Development of a 24-h Preservation Protocol of Forearm Vascularized Composite Allotransplants in Nonhuman Primates Using Subnormothermic Machine PerfusionHaïzam Oubari, MD0Loïc Van Dieren, MS1Yanis Berkane, MD2Lucile Cabanel, MD3Mark A. Randolph, MAS4Curtis L. Cetrulo, Jr, MD5Alexandre G. Lellouch, MD6Korkut Uygun, PhD71 Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.1 Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.1 Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.1 Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.1 Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.1 Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.1 Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.1 Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.Background. Subnormothermic machine perfusion shows promise as a viable alternative to static cold storage for prolonged preservation of vascularized composite allografts. To date, most studies have been conducted in nonprimate models, and we report its first utilization in a cynomolgus forearm preclinical model for 24-h preservation. Methods. Forearms were procured from nonhuman primates weighing between 5 and 8 kg. Two perfusion protocols were implemented. In group 1 (n = 6), limbs were perfused with 1.5 L of recirculating Steen; the perfusate flow was adjusted to maintain stable vascular pressures. In group 2 (n = 6), limbs were perfused with a Steen+ solution, doubling the albumin concentration, with a full-volume exchange at mid-perfusion under a stable low-flow regimen. Dynamic and metabolic parameters, histological analysis, and response to neurostimulation were assessed. Results. After 24 h of continuous perfusion, mean weight gain was 24.8 ± 5.5% in group 1 and 8.0 ± 4.7% in group 2. Perfusion and metabolic parameters indicated the onset of a compartment syndrome in group 1 with an increase in resistance, lactate, and potassium production at mid-perfusion. In group 2, dynamic and metabolic parameters remained stable for 24 h, and histological analysis showed well-preserved tissues. Finally, in group 2, limbs exhibited muscular contraction recovery quantified at 2.4/5 ± 0.89 after 24 h compared with 0/5 after 3 h of ischemia or after perfusion in group 1. Conclusions. Successful 24-h perfusion and muscle contractility restoration demonstrate promising outcomes for vascularized composite allograft preservation and reconditioning.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001849 |
| spellingShingle | Haïzam Oubari, MD Loïc Van Dieren, MS Yanis Berkane, MD Lucile Cabanel, MD Mark A. Randolph, MAS Curtis L. Cetrulo, Jr, MD Alexandre G. Lellouch, MD Korkut Uygun, PhD Development of a 24-h Preservation Protocol of Forearm Vascularized Composite Allotransplants in Nonhuman Primates Using Subnormothermic Machine Perfusion Transplantation Direct |
| title | Development of a 24-h Preservation Protocol of Forearm Vascularized Composite Allotransplants in Nonhuman Primates Using Subnormothermic Machine Perfusion |
| title_full | Development of a 24-h Preservation Protocol of Forearm Vascularized Composite Allotransplants in Nonhuman Primates Using Subnormothermic Machine Perfusion |
| title_fullStr | Development of a 24-h Preservation Protocol of Forearm Vascularized Composite Allotransplants in Nonhuman Primates Using Subnormothermic Machine Perfusion |
| title_full_unstemmed | Development of a 24-h Preservation Protocol of Forearm Vascularized Composite Allotransplants in Nonhuman Primates Using Subnormothermic Machine Perfusion |
| title_short | Development of a 24-h Preservation Protocol of Forearm Vascularized Composite Allotransplants in Nonhuman Primates Using Subnormothermic Machine Perfusion |
| title_sort | development of a 24 h preservation protocol of forearm vascularized composite allotransplants in nonhuman primates using subnormothermic machine perfusion |
| url | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001849 |
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