• J. Thorac. Cardiovasc. Surg. · Apr 2017

    Myocardial rescue with autologous mitochondrial transplantation in a porcine model of ischemia/reperfusion.

    • Aditya K Kaza, Isaac Wamala, Ingeborg Friehs, Joseph D Kuebler, Rahul H Rathod, Ignacio Berra, Maria Ericsson, Rouan Yao, Jerusha K Thedsanamoorthy, David Zurakowski, Sidney Levitsky, Pedro J Del Nido, Douglas B Cowan, and James D McCully.
    • Department of Cardiac Surgery, Boston Children's Hospital, Boston, Mass.
    • J. Thorac. Cardiovasc. Surg. 2017 Apr 1; 153 (4): 934-943.

    ObjectiveTo demonstrate the clinical efficacy of autologous mitochondrial transplantation in preparation for translation to human application using an in vivo swine model.MethodsA left mini-thoracotomy was performed on Yorkshire pigs. The pectoralis major was dissected, and skeletal muscle tissue was removed and used for the isolation of autologous mitochondria. The heart was subjected to regional ischemia (RI) by temporarily snaring the circumflex artery. After 24 minutes of RI, hearts received 8 × 0.1 mL injections of vehicle (vehicle-only group; n = 6) or vehicle containing mitochondria (mitochondria group; n = 6) into the area at risk (AAR), and the snare was released. The thoracotomy was closed, and the pigs were allowed to recover for 4 weeks.ResultsLevels of creatine kinase-MB isoenzyme and cardiac troponin I were significantly increased (P = .006) in the vehicle-only group compared with the mitochondria group. Immune, inflammatory, and cytokine activation markers showed no significant difference between groups. There was no significant between-group difference in the AAR (P = .48), but infarct size was significantly greater in the vehicle group (P = .004). Echocardiography showed no significant differences in global function. Histochemistry and transmission electron microscopy revealed damaged heart tissue in the vehicle group that was not apparent in the mitochondria group. T2-weighted magnetic resonance imaging and histology demonstrated that the injected mitochondria were present for 4 weeks.ConclusionsAutologous mitochondrial transplantation provides a novel technique to significantly enhance myocardial cell viability following ischemia and reperfusion in the clinically relevant swine model.Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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