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Significantly Improved Cold Preservation of Rat Hind Limb Vascularized Composite Allografts Using the New PrC-210 Free Radical Scavenger.
Fahl, William E; Nkana, Zeeda H; Gitter, Maya M; Zeng, Weifeng; Dingle, Aaron M.
Afiliación
  • Fahl WE; Wisconsin Institute of Medical Research, University of Wisconsin-Madison, 111 Highland Ave., Madison, WI 53705, USA.
  • Nkana ZH; Division of Plastic Surgery, Department of Surgery, University of Wisconsin-Madison, 600 Highland Ave., Madison, WI 53705, USA.
  • Gitter MM; Wisconsin Institute of Medical Research, University of Wisconsin-Madison, 111 Highland Ave., Madison, WI 53705, USA.
  • Zeng W; Division of Plastic Surgery, Department of Surgery, University of Wisconsin-Madison, 600 Highland Ave., Madison, WI 53705, USA.
  • Dingle AM; Division of Plastic Surgery, Department of Surgery, University of Wisconsin-Madison, 600 Highland Ave., Madison, WI 53705, USA.
Int J Mol Sci ; 25(3)2024 Jan 28.
Article en En | MEDLINE | ID: mdl-38338887
ABSTRACT
Vascularized composite allotransplantation (VCA) represents a promising reconstructive solution primarily conducted to improve quality of life. However, tissue damage caused by cold-ischemia (CI) storage prior to transplant represents a major factor limiting widespread application. This study investigates the addition of the novel free radical scavenger PrC-210 to UW Organ Preservation Solution (UW Solution) to suppress CI-induced skeletal muscle injury in a rat hind limb amputation model. Lewis rats received systemic perfusion of UW solution +/- PrC-210 (0 mM control, 10 mM, 20 mM, 30 mM, or 40 mM), followed by bilateral transfemoral amputation. Limbs were stored in 40 mL of the same perfusate at 4 °C for 48 h. Muscle punch biopsies were taken at set times over the 48 h cold-storage period and analyzed for caspase-3,7 activity, cytochrome C levels, and qualitative histology. A single 15 s perfusion of PrC-210-containing UW Solution conferred a dose-dependent reduction in CI-induced muscle cell death over 48 h. In the presence of PrC-210, muscle cell mitochondrial cytochrome C release was equivalent to 0 h controls, with profound reductions in the caspase-3,7 apoptotic marker that correlated with limb histology. PrC-210 conferred complete prevention of ROS-induced mitochondrial lysis in vitro, as measured by cytochrome C release. We conclude that the addition of 30 mM PrC210 to UW Solution conferred the most consistent reduction in CI limb damage, and it warrants further investigation for clinical application in the VCA setting.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos de Sulfhidrilo / Daño por Reperfusión / Soluciones Preservantes de Órganos / Diaminas / Aloinjertos Compuestos Tipo de estudio: Prognostic_studies / Qualitative_research Aspecto: Patient_preference Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos de Sulfhidrilo / Daño por Reperfusión / Soluciones Preservantes de Órganos / Diaminas / Aloinjertos Compuestos Tipo de estudio: Prognostic_studies / Qualitative_research Aspecto: Patient_preference Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza