Preischemic autologous mitochondrial transplantation by intracoronary injection for myocardial protection.

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 × 10) or buffer (vehicle [Veh]) were delivered as a single bolus (MT) or serially (10 injections over 60 minutes; MT). 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, MT and MT hearts had significantly increased CBF that persisted throughout reperfusion (Veh vs MT and MT; P = .04). MT and MT showed a significantly enhanced ejection fraction (Veh vs MT, P < .001; Veh vs MT, P = .04) and developed pressure (Veh vs MT, P < .001; Veh vs MT, P = .03). Regional function, assessed through segmental shortening (Veh vs MT, P = .03; Veh vs MT, P < .001), fractional shortening (Veh vs MT, P < .001; Veh vs MT, P = .04), and strain analysis (Veh vs MT, P = .002; Veh vs MT, 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 MT and MT, 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.