Transplantation of Autologously‐Derived Mitochondria Protects the Heart from Ischemia‐Reperfusion Injury

The ability of mitochondria to regulate myocardial homeostasis and energetic requirements is compromised following reduction or cessation of blood flow resulting in tissue necrosis and impaired cardiac function. We hypothesized that transplantation of autologously‐derived mitochondria immediately prior to reperfusion would ameliorate these effects. NZW rabbits were subjected to regional ischemia (RI) by temporarily snaring the left anterior descending artery for 30 min. Following 29 min. RI, mitochondria (RI‐Mito) or vehicle (RI‐V) were injected into the RI zone and the hearts recovered for 4 weeks. RI‐Mito decreased infarct size (7.9±2.9%) as compared to RI‐V (34.2±3.3%; P<0.05). Serial echocardiograms showed RI‐Mito hearts returned to normal contraction in early reperfusion but RI‐V hearts had persistent hypokinesia in the RI zone. The injected mitochondria were retained in the myocardium with the majority located in the interstitium but many were internalized by cardiomyocytes. The transplanted mitochondria enhanced oxygen consumption and upregulated proteomic pathways for enhanced myocardial energetics. Our results demonstrate that the transplantation of autologously‐derived mitochondria into the RI zone just prior to reperfusion provides cardioprotection both intracellularly and extracellularly to significantly decrease necrosis and enhance post‐ischemic functional recovery.

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