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J Thorac Cardiovasc Surg. 2017 Apr;153(4):934-943. doi: 10.1016/j.jtcvs.2016.10.077. Epub 2016 Nov 15.

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

Author information

1
Department of Cardiac Surgery, Boston Children's Hospital, Boston, Mass.
2
Department of Cardiology, Boston Children's Hospital, Boston, Mass.
3
Electron Microscopy Facility, Department of Cell Biology, Boston, Mass.
4
Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Mass.
5
Division of Cardiac Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.
6
Department of Cardiac Surgery, Boston Children's Hospital, Boston, Mass. Electronic address: james_mccully@hms.harvard.edu.

Abstract

OBJECTIVE:

To demonstrate the clinical efficacy of autologous mitochondrial transplantation in preparation for translation to human application using an in vivo swine model.

METHODS:

A 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.

RESULTS:

Levels 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.

CONCLUSIONS:

Autologous mitochondrial transplantation provides a novel technique to significantly enhance myocardial cell viability following ischemia and reperfusion in the clinically relevant swine model.

KEYWORDS:

infarct; ischemia; mitochondria; reperfusion

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