Mitochondrial transplantation ameliorates acute limb ischemia
| Autor: | David Blitzer, Caitlyn Rogers, Giovanna Ramirez-Barbieri, Ilias P. Doulamis, Pedro J. del Nido, Borami Shin, Arzoo Orfany, Carlos Galán Arriola, Kamila Moskowitzova, Alvise Guariento, James D. McCully |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Acute ischemia Hindlimb Mitochondrial transplantation Muscle Vastus medialis Ischemia 030204 cardiovascular system & hematology Mitochondrion Mice 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals 030212 general & internal medicine Tourniquet business.industry Skeletal muscle medicine.disease Mitochondria Mice Inbred C57BL Transplantation Disease Models Animal medicine.anatomical_structure Endocrinology Apoptosis Reperfusion Injury Acute Disease Surgery Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of Vascular Surgery. 71:1014-1026 |
| ISSN: | 0741-5214 |
| Popis: | Objective Acute limb ischemia (ALI), the most challenging form of ischemia-reperfusion injury (IRI) in skeletal muscle tissue, leads to decreased skeletal muscle viability and limb function. Mitochondrial injury has been shown to play a key role in skeletal muscle IRI. In previous studies, we have demonstrated that mitochondrial transplantation (MT) is an efficacious therapeutic strategy to replace or to augment mitochondria damaged by IRI, allowing enhanced muscle viability and function in cardiac tissue. In this study, we investigated the efficacy of MT in a murine ALI model. Methods C57BL/6J mice (male, 10-12 weeks) were used in a model of ALI. Ischemia was induced by applying a tourniquet on the left hindlimb. After 2 hours of ischemia, the tourniquet was released, and reperfusion of the hindlimb was re-established; either vehicle alone (n = 15) or vehicle containing mitochondria (n = 33) was injected directly into all the muscles of the hindlimb. Mitochondria were delivered at concentrations of 1 × 106 to 1 × 109 per gram wet weight to each muscle, and the animals were allowed to recover. Sham mice received no ischemia or injections but were anesthetized for 2 hours and allowed to recover. After 24 hours of recovery, limb function was assessed by DigiGait (Mouse Specifics Inc, Boston, Mass), and animals were euthanized; the gastrocnemius, soleus, and vastus medialis muscles were collected for analysis. Results After 24 hours of hindlimb reperfusion, infarct size (percentage of total mass) and apoptosis were significantly decreased (P Conclusions MT ameliorates skeletal muscle injury and enhances hindlimb function in the murine model of ALI. |
| Databáze: | OpenAIRE |
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