Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection

被引:175
作者
Cowan, Douglas B. [1 ,2 ]
Yao, Rouan [1 ,2 ]
Akurathi, Vamsidhar [2 ,3 ]
Snay, Erin R. [2 ,3 ]
Thedsanamoorthy, Jerusha K. [1 ,2 ]
Zurakowski, David [1 ,2 ,4 ]
Ericsson, Maria [5 ]
Friehs, Ingeborg [2 ,4 ]
Wu, Yaotang [2 ,3 ]
Levitsky, Sidney [2 ,6 ]
del Nido, Pedro J. [2 ,4 ]
Packard, Alan B. [2 ,3 ]
McCully, James D. [2 ,4 ]
机构
[1] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA
[2] Harvard Med Sch, Boston, MA 02115 USA
[3] Boston Childrens Hosp, Dept Radiol, Boston, MA USA
[4] Boston Childrens Hosp, Dept Cardiac Surg, Boston, MA 02115 USA
[5] Harvard Med Sch, Dept Cell Biol, Boston, MA USA
[6] Beth Israel Deaconess Med Ctr, Dept Cardiothorac Surg, Boston, MA 02215 USA
基金
美国国家卫生研究院;
关键词
REPERFUSION; INJURY; TRANSPLANTATION; CHANNELS; PROTECTS; NECROSIS; CALCIUM;
D O I
10.1371/journal.pone.0160889
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have previously shown that transplantation of autologously derived, respiration-competent mitochondria by direct injection into the heart following transient ischemia and reperfusion enhances cell viability and contractile function. To increase the therapeutic potential of this approach, we investigated whether exogenous mitochondria can be effectively delivered through the coronary vasculature to protect the ischemic myocardium and studied the fate of these transplanted organelles in the heart. Langendorff-perfused rabbit hearts were subjected to 30 minutes of ischemia and then reperfused for 10 minutes. Mitochondria were labeled with F-18-rhodamine 6G and iron oxide nanoparticles. The labeled mitochondria were either directly injected into the ischemic region or delivered by vascular perfusion through the coronary arteries at the onset of reperfusion. These hearts were used for positron emission tomography, microcomputed tomography, and magnetic resonance imaging with subsequent microscopic analyses of tissue sections to confirm the uptake and distribution of exogenous mitochondria. Injected mitochondria were localized near the site of delivery; while, vascular perfusion of mitochondria resulted in rapid and extensive dispersal throughout the heart. Both injected and perfused mitochondria were observed in interstitial spaces and were associated with blood vessels and cardiomyocytes. To determine the efficacy of vascular perfusion of mitochondria, an additional group of rabbit hearts were subjected to 30 minutes of regional ischemia and reperfused for 120 minutes. Immediately following regional ischemia, the hearts received unlabeled, autologous mitochondria delivered through the coronary arteries. Autologous mitochondria perfused through the coronary vasculature significantly decreased infarct size and significantly enhanced post-ischemic myocardial function. In conclusion, the delivery of mitochondria through the coronary arteries resulted in their rapid integration and widespread distribution throughout the heart and provided cardioprotection from ischemia-reperfusion injury.
引用
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页数:19
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