Mitochondrial transplantation prolongs cold ischemia time in murine heart transplantation.

Autor:	Moskowitzova K; Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts, USA., Shin B; Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts, USA., Liu K; Department of Pulmonary and Respiratory Diseases, Boston Children's Hospital, Boston, Massachusetts, USA., Ramirez-Barbieri G; Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts, USA., Guariento A; Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts, USA., Blitzer D; Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts, USA., Thedsanamoorthy JK; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA., Yao R; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA., Snay ER; Department of Radiology, Boston Children's Hospital, Boston, Massachusetts, USA., Inkster JAH; Department of Radiology, Boston Children's Hospital, Boston, Massachusetts, USA., Orfany A; Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts, USA., Zurakowski D; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA., Cowan DB; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA., Packard AB; Department of Radiology, Boston Children's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA., Visner GA; Department of Pulmonary and Respiratory Diseases, Boston Children's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA., Del Nido PJ; Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA., McCully JD; Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA. Electronic address: james.mccully@childrens.harvard.edu.
Jazyk:	angličtina
Zdroj:	The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation [J Heart Lung Transplant] 2019 Jan; Vol. 38 (1), pp. 92-99. Date of Electronic Publication: 2018 Sep 28.
DOI:	10.1016/j.healun.2018.09.025
Abstrakt:	Background: Cold ischemia time (CIT) causes ischemia‒reperfusion injury to the mitochondria and detrimentally effects myocardial function and tissue viability. Mitochondrial transplantation replaces damaged mitochondria and enhances myocardial function and tissue viability. Herein we investigated the efficacy of mitochondrial transplantation in enhancing graft function and viability after prolonged CIT. Methods: Heterotopic heart transplantation was performed in C57BL/6J mice. Upon heart harvesting from C57BL/6J donors, 0.5 ml of either mitochondria (1 × 10 8 in respiration buffer; mitochondria group) or respiration buffer (vehicle group) was delivered antegrade to the coronary arteries via injection to the coronary ostium. The hearts were excised and preserved for 29 ± 0.3 hours in cold saline (4°C). The hearts were then heterotopically transplanted. A second injection of either mitochondria (1 × 10 8 ) or respiration buffer (vehicle) was delivered antegrade to the coronary arteries 5 minutes after transplantation. Grafts were analyzed for 24 hours. Beating score, graft function, and tissue injury were measured. Results: Beating score, calculated ejection fraction, and shortening fraction were significantly enhanced (p < 0.05), whereas necrosis and neutrophil infiltration were significantly decreased (p < 0.05) in the mitochondria group as compared with the vehicle group at 24 hours of reperfusion. Transmission electron microscopy showed the presence of contraction bands in vehicle but not in mitochondria grafts. Conclusions: Mitochondrial transplantation prolongs CIT to 29 hours in the murine heart transplantation model, significantly enhances graft function, and decreases graft tissue injury. Mitochondrial transplantation may provide a means to reduce graft failure and improve transplantation outcomes after prolonged CIT. (Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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