Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Mass.
Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Mass.
J Thorac Cardiovasc Surg. 2020 Aug;160(2):e15-e29. doi: 10.1016/j.jtcvs.2019.06.111. Epub 2019 Aug 28.
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).
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.
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).
Preischemic MT by single or serial intracoronary injections provides prophylactic myocardial protection from IRI, significantly decreasing infarct size and enhancing global and regional function.
研究缺血前冠状动脉内自体线粒体移植（MT）作为预防猪局部缺血再灌注损伤（IRI）模型心肌保护的治疗策略。
将左冠状动脉插管到约克夏猪（n=26）中。将线粒体（1×10）或缓冲液（载体[Veh]）作为单次推注（MT）或连续推注（60 分钟内 10 次注射；MT）给予。在注射后 15 分钟，通过套扎左前降支使心脏经历短暂的区域缺血（RI）。在 30 分钟 RI 后，松开套扎，心脏再灌注 120 分钟。
在预 RI 期间，冠状动脉血流（CBF）和心肌功能暂时增加。在 30 分钟 RI 后，MT 和 MT 心脏的 CBF 明显增加，并在再灌注期间持续增加（Veh 与 MT 和 MT；P=0.04）。MT 和 MT 表现出明显增强的射血分数（Veh 与 MT，P<0.001；Veh 与 MT，P=0.04）和发展压力（Veh 与 MT，P<0.001；Veh 与 MT，P=0.03）。通过节段缩短（Veh 与 MT，P=0.03；Veh 与 MT，P<0.001）、分数缩短（Veh 与 MT，P<0.001；Veh 与 MT，P=0.04）和应变分析（Veh 与 MT，P=0.002；Veh 与 MT，P=0.003）评估的局部功能也得到了显著改善。尽管治疗组之间的危险区域没有差异，但在两个 MT 组中，梗塞面积都明显减小（Veh 与 MT 和 MT，P<0.001）。
单次或连续冠状动脉内 MT 可提供预防性心肌保护，防止 IRI，显著减小梗塞面积并增强整体和局部功能。
