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Delayed Transplantation of Autologous Mitochondria for Cardioprotection in a Porcine Model.

David Blitzer,A. Guariento,I. Doulamis,Borami Shin,Kamila Moskowitzova,G. Barbieri,Arzoo Orfany,P. D. del Nido,J. McCully

Published 2020 in Annals of Thoracic Surgery

ABSTRACT

BACKGROUND We have previously demonstrated the efficacy of mitochondrial transplantation for the treatment of ischemia-reperfusion injury (IRI). We now investigate the efficacy of delayed mitochondrial transplantation (MT) via intracoronary administration in a model of regional IRI as a strategy for cardioprotection. METHODS Female Yorkshire pigs (40-50 kg; n=16) underwent 30 minutes of ischemia by snaring of the left anterior descending artery (LAD) and the hearts were then reperfused for 120 minutes. At that point, Vehicle only or Autologous Mitochondria (1x109 in 5 mL vehicle) were delivered as a bolus to the left coronary ostium followed by a further 120-minute reperfusion. RESULTS Echocardiographic analysis demonstrated that hearts receiving delayed MT after regional IRI had enhanced ejection fraction (p=0.019), fractional shortening (p=0.022) and fractional area change (p=0.011) at 240 minutes of reperfusion compared with the untreated animals. At the end of reperfusion there was a difference between groups in measures of global LV function such as LV end diastolic pressure (p=0.015) and rate of rise of LV pressure (dp/dt max) (p=0.021). There were no significant differences between groups in the area at risk (p=0.48). Infarct size (% area at risk) was significantly decreased in hearts receiving MT as compared to hearts receiving vehicle only (p<0.001). CONCLUSIONS Delayed MT by intracoronary injection significantly decreases myocardial infarct size, increasing regional and global myocardial function. These results suggest that this can be a viable treatment modality in IRI, thus reducing long-term morbidity and mortality in cardiac surgical patients.

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