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. 2020 Aug;160(2):e15-e29.
doi: 10.1016/j.jtcvs.2019.06.111. Epub 2019 Aug 28.

Preischemic autologous mitochondrial transplantation by intracoronary injection for myocardial protection

Alvise Guariento  1 , David Blitzer  1 , Ilias Doulamis  1 , Borami Shin  1 , Kamila Moskowitzova  1 , Arzoo Orfany  1 , Giovanna Ramirez-Barbieri  1 , Steven J Staffa  2 , David Zurakowski  2 , Pedro J Del Nido  1 , James D McCully  3
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Free article

Preischemic autologous mitochondrial transplantation by intracoronary injection for myocardial protection

Alvise Guariento et al. J Thorac Cardiovasc Surg. 2020 Aug.
Free article

Abstract

Objective: To investigate preischemic intracoronary autologous mitochondrial transplantation (MT) as a therapeutic strategy for prophylactic myocardial protection in a porcine model of regional ischemia-reperfusion injury (IRI).

Methods: The left coronary artery was cannulated in Yorkshire pigs (n = 26). Mitochondria (1 × 109) or buffer (vehicle [Veh]) were delivered as a single bolus (MTS) or serially (10 injections over 60 minutes; MTSS). At 15 minutes after injection, the heart was subjected to temporary regional ischemia (RI) by snaring the left anterior descending artery. After 30 minutes of RI, the snare was released, and the heart was reperfused for 120 minutes.

Results: Coronary blood flow (CBF) and myocardial function were increased temporarily during the pre-RI period. Following 30 minutes of RI, MTS and MTSS hearts had significantly increased CBF that persisted throughout reperfusion (Veh vs MTS and MTSS; P = .04). MTS and MTSS showed a significantly enhanced ejection fraction (Veh vs MTS, P < .001; Veh vs MTSS, P = .04) and developed pressure (Veh vs MTS, P < .001; Veh vs MTSS, P = .03). Regional function, assessed through segmental shortening (Veh vs MTS, P = .03; Veh vs MTSS, P < .001), fractional shortening (Veh vs MTS, P < .001; Veh vs MTSS, P = .04), and strain analysis (Veh vs MTS, P = .002; Veh vs MTSS, P = .003), was also significantly improved. Although there was no difference in the area at risk between treatment groups, infarct size was significantly reduced in both MT groups (Veh vs MTS and MTSS, P < .001).

Conclusions: Preischemic MT by single or serial intracoronary injections provides prophylactic myocardial protection from IRI, significantly decreasing infarct size and enhancing global and regional function.

Keywords: ischemia/reperfusion injury heart; myocardial ischemia; myocardial protection.

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