Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.
Department of Pulmonary and Respiratory Diseases, Boston Children's Hospital, Boston, Massachusetts, USA.
J Heart Lung Transplant. 2019 Jan;38(1):92-99. doi: 10.1016/j.healun.2018.09.025. Epub 2018 Sep 28.
Cold ischemia time (CIT) causes ischemia‒reperfusion injury to the mitochondria and detrimentally effects myocardial function and tissue viability. Mitochondrial transplantation replaces damaged mitochondria and enhances myocardial function and tissue viability. Herein we investigated the efficacy of mitochondrial transplantation in enhancing graft function and viability after prolonged CIT.
Heterotopic heart transplantation was performed in C57BL/6J mice. Upon heart harvesting from C57BL/6J donors, 0.5 ml of either mitochondria (1 × 10 in respiration buffer; mitochondria group) or respiration buffer (vehicle group) was delivered antegrade to the coronary arteries via injection to the coronary ostium. The hearts were excised and preserved for 29 ± 0.3 hours in cold saline (4°C). The hearts were then heterotopically transplanted. A second injection of either mitochondria (1 × 10) or respiration buffer (vehicle) was delivered antegrade to the coronary arteries 5 minutes after transplantation. Grafts were analyzed for 24 hours. Beating score, graft function, and tissue injury were measured.
Beating score, calculated ejection fraction, and shortening fraction were significantly enhanced (p < 0.05), whereas necrosis and neutrophil infiltration were significantly decreased (p < 0.05) in the mitochondria group as compared with the vehicle group at 24 hours of reperfusion. Transmission electron microscopy showed the presence of contraction bands in vehicle but not in mitochondria grafts.
Mitochondrial transplantation prolongs CIT to 29 hours in the murine heart transplantation model, significantly enhances graft function, and decreases graft tissue injury. Mitochondrial transplantation may provide a means to reduce graft failure and improve transplantation outcomes after prolonged CIT.
冷缺血时间 (CIT) 会导致线粒体缺血再灌注损伤，从而对心肌功能和组织活力产生不利影响。线粒体移植可替代受损的线粒体，增强心肌功能和组织活力。在此，我们研究了线粒体移植在延长 CIT 后增强移植物功能和活力的效果。
在 C57BL/6J 小鼠中进行异位心脏移植。从 C57BL/6J 供体中取出心脏后，通过向冠状动脉口内注射，将 0.5 毫升的线粒体（呼吸缓冲液中的 1×10 个；线粒体组）或呼吸缓冲液（载体组）顺行递送至冠状动脉。将心脏取出并在冷盐水中（4°C）保存 29±0.3 小时。然后将心脏异位移植。在移植后 5 分钟，通过向冠状动脉再次注射线粒体（1×10）或呼吸缓冲液（载体）。分析移植物 24 小时。测量跳动评分、移植物功能和组织损伤。
与载体组相比，在再灌注 24 小时时，线粒体组的跳动评分、计算的射血分数和缩短分数显著提高（p<0.05），而坏死和中性粒细胞浸润显著降低（p<0.05）。透射电子显微镜显示，在载体组的移植物中存在收缩带，但在线粒体组的移植物中没有。
线粒体移植将小鼠心脏移植模型中的 CIT 延长至 29 小时，显著增强了移植物功能，并降低了移植物组织损伤。线粒体移植可能为减少 CIT 延长后的移植物失功和改善移植结果提供一种手段。
