Moderate LMWH Anticoagulation Improves Success Rate of Hind Limb Allotransplantation in Mice
Background:. The mouse hind limb model represents a powerful research tool in vascularized composite tissue allotransplantation, but its applicability is limited due to poor graft survival (62%–83%). Vascular thrombosis and massive hemorrhage are the major causes for these drop-outs. We hypothesize...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2023-09-01
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| Series: | Plastic and Reconstructive Surgery, Global Open |
| Online Access: | http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000005249 |
| _version_ | 1797375019016257536 |
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| author | Barbara Kern, MD Muhammad-Imtiaz Ashraf, PhD Anja Reutzel-Selke, PhD Joerg Mengwasser, PhD Dietrich Polenz Edward Michaelis, MD Johann Pratschke, MD, PhD Stefan G. Tullius, MD, PhD Christian Witzel, MD, PhD Igor M. Sauer, MD, PhD |
| author_facet | Barbara Kern, MD Muhammad-Imtiaz Ashraf, PhD Anja Reutzel-Selke, PhD Joerg Mengwasser, PhD Dietrich Polenz Edward Michaelis, MD Johann Pratschke, MD, PhD Stefan G. Tullius, MD, PhD Christian Witzel, MD, PhD Igor M. Sauer, MD, PhD |
| author_sort | Barbara Kern, MD |
| collection | DOAJ |
| description | Background:. The mouse hind limb model represents a powerful research tool in vascularized composite tissue allotransplantation, but its applicability is limited due to poor graft survival (62%–83%). Vascular thrombosis and massive hemorrhage are the major causes for these drop-outs. We hypothesize that because of better anticoagulation effect and lower risk of thrombocytopenia, application of low molecular weight heparin (LMWH) will minimize vascular complications and enhance graft and animal survival.
Methods:. Fifty allogeneic hind limb transplantations were performed (C57BL/6 to DBA/2 mice) using five different anticoagulation protocols. Bleeding and thromboembolic events were recorded macroscopically by postoperative hemorrhage and livid discoloration of the graft, respectively. Graft perfusion and survival were monitored daily by capillary-refill-time of graft toes within 2–3 seconds. Vascular congestion and tissue necrosis were examined by histological evaluation of hematoxylin-eosin-stained tissue sections.
Results:. All transplantations were technically successful. Increase in thromboembolic events and a concomitant decrease in bleeding events were observed with the decreasing concentration of heparin in the perfusion solution. Although treatment of donor and recipient with low dose of LMWH could not reduce thromboembolic events, moderate dose effectively reduced these events. Compared with the poor outcome of graft perfusion with heparin alone, additional treatment of donor and recipient with low dose of LMWH improved graft and animal survival by 18%. Interestingly, animals treated with moderate dose of LMWH demonstrated 100% graft and animal survival.
Conclusions:. Treatment of donor and recipient mice with a moderate dose of LMWH prevents vascular complications and improves the outcome of murine hind limb transplants. |
| first_indexed | 2024-03-08T19:16:08Z |
| format | Article |
| id | doaj.art-098561d647b643bf92f5c1972a95c797 |
| institution | Directory Open Access Journal |
| issn | 2169-7574 |
| language | English |
| last_indexed | 2024-03-08T19:16:08Z |
| publishDate | 2023-09-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Plastic and Reconstructive Surgery, Global Open |
| spelling | doaj.art-098561d647b643bf92f5c1972a95c7972023-12-27T06:49:45ZengWolters KluwerPlastic and Reconstructive Surgery, Global Open2169-75742023-09-01119e524910.1097/GOX.0000000000005249202309000-00036Moderate LMWH Anticoagulation Improves Success Rate of Hind Limb Allotransplantation in MiceBarbara Kern, MD0Muhammad-Imtiaz Ashraf, PhD1Anja Reutzel-Selke, PhD2Joerg Mengwasser, PhD3Dietrich Polenz4Edward Michaelis, MD5Johann Pratschke, MD, PhD6Stefan G. Tullius, MD, PhD7Christian Witzel, MD, PhD8Igor M. Sauer, MD, PhD9From the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyFrom the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyFrom the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyFrom the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyFrom the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany¶ Department of Pathology, Charité – Universitätsmedizin Berlin, Berlin, GermanyFrom the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany** Division of Transplant Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.† Department of Plastic Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyFrom the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyBackground:. The mouse hind limb model represents a powerful research tool in vascularized composite tissue allotransplantation, but its applicability is limited due to poor graft survival (62%–83%). Vascular thrombosis and massive hemorrhage are the major causes for these drop-outs. We hypothesize that because of better anticoagulation effect and lower risk of thrombocytopenia, application of low molecular weight heparin (LMWH) will minimize vascular complications and enhance graft and animal survival. Methods:. Fifty allogeneic hind limb transplantations were performed (C57BL/6 to DBA/2 mice) using five different anticoagulation protocols. Bleeding and thromboembolic events were recorded macroscopically by postoperative hemorrhage and livid discoloration of the graft, respectively. Graft perfusion and survival were monitored daily by capillary-refill-time of graft toes within 2–3 seconds. Vascular congestion and tissue necrosis were examined by histological evaluation of hematoxylin-eosin-stained tissue sections. Results:. All transplantations were technically successful. Increase in thromboembolic events and a concomitant decrease in bleeding events were observed with the decreasing concentration of heparin in the perfusion solution. Although treatment of donor and recipient with low dose of LMWH could not reduce thromboembolic events, moderate dose effectively reduced these events. Compared with the poor outcome of graft perfusion with heparin alone, additional treatment of donor and recipient with low dose of LMWH improved graft and animal survival by 18%. Interestingly, animals treated with moderate dose of LMWH demonstrated 100% graft and animal survival. Conclusions:. Treatment of donor and recipient mice with a moderate dose of LMWH prevents vascular complications and improves the outcome of murine hind limb transplants.http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000005249 |
| spellingShingle | Barbara Kern, MD Muhammad-Imtiaz Ashraf, PhD Anja Reutzel-Selke, PhD Joerg Mengwasser, PhD Dietrich Polenz Edward Michaelis, MD Johann Pratschke, MD, PhD Stefan G. Tullius, MD, PhD Christian Witzel, MD, PhD Igor M. Sauer, MD, PhD Moderate LMWH Anticoagulation Improves Success Rate of Hind Limb Allotransplantation in Mice Plastic and Reconstructive Surgery, Global Open |
| title | Moderate LMWH Anticoagulation Improves Success Rate of Hind Limb Allotransplantation in Mice |
| title_full | Moderate LMWH Anticoagulation Improves Success Rate of Hind Limb Allotransplantation in Mice |
| title_fullStr | Moderate LMWH Anticoagulation Improves Success Rate of Hind Limb Allotransplantation in Mice |
| title_full_unstemmed | Moderate LMWH Anticoagulation Improves Success Rate of Hind Limb Allotransplantation in Mice |
| title_short | Moderate LMWH Anticoagulation Improves Success Rate of Hind Limb Allotransplantation in Mice |
| title_sort | moderate lmwh anticoagulation improves success rate of hind limb allotransplantation in mice |
| url | http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000005249 |
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