Thatte Hemant S, Rousou Laki, Hussaini Bader E, Lu Xiu-Gui, Treanor Patrick R, Khuri Shukri F
Department of Surgery, Harvard Medical School, VA Boston Healthcare System, Boston, MA 02132, USA.
Circulation. 2009 Oct 27;120(17):1704-13. doi: 10.1161/CIRCULATIONAHA.108.808907. Epub 2009 Oct 12.
Injury to myocytes, endocardium, and the coronary endothelium during harvesting and storage can compromise outcomes after heart transplantation. Safeguarding of structure and function of cardiomyocytes and endothelium in donor hearts may lead to improved patient survival after transplantation. Information gained from porcine hearts stored in standard transplant solution was used to design a superior preservation solution that would optimally protect and maintain organs from beating heart and/or nonbeating heart donors during long-term storage.
Multiphoton microscopy was used to image deep within cardiac biopsies and coronary artery tissue harvested from porcine hearts obtained from beating heart and nonbeating heart donors for analysis of myocyte and endothelial cell structure and function. Cell structural integrity and viability, calcium mobilization, and nitric oxide generation were determined with fluorescence viability markers, immunofluorescence, and Western blots. During hypothermic storage in standard preservation solution, Celsior, myocyte, and endothelial viability was markedly attenuated in hearts obtained from beating heart donors. In contrast, hearts from beating and nonbeating heart donors stored in the newly formulated Somah solution demonstrated an increase in high-energy phosphate levels, protection of cardiac myocyte viability, mitochondrial membrane polarization, and structural proteins. Similarly, coronary artery endothelial organization and function, calcium mobilization, and nitric oxide generation were well maintained during temporal storage in Somah.
The Celsior preservation solution in clinical use today has led to a profound decline in cardiomyocyte and endothelial cell viability, whereas the newly designed Somah solution has safeguarded myocyte and endothelial integrity and function during organ storage. Use of Somah as a storage medium may lead to optimized graft function and long-term patient survival after transplantation.
心脏采集和保存过程中，心肌细胞、心内膜和冠状动脉内皮的损伤会影响心脏移植后的预后。保护供体心脏中心肌细胞和内皮的结构与功能可能会提高移植后患者的生存率。从保存在标准移植溶液中的猪心脏获得的信息被用于设计一种更优的保存溶液，该溶液能在长期保存期间最佳地保护和维持来自跳动心脏和/或非跳动心脏供体的器官。
利用多光子显微镜对从跳动心脏和非跳动心脏供体获取的猪心脏的心脏活检组织和冠状动脉组织进行深部成像，以分析心肌细胞和内皮细胞的结构与功能。通过荧光活力标记、免疫荧光和蛋白质印迹法测定细胞结构完整性、活力、钙动员和一氧化氮生成。在标准保存溶液Celsior中低温保存期间，来自跳动心脏供体的心脏中心肌细胞和内皮活力明显减弱。相比之下，保存在新配制的Somah溶液中的来自跳动和非跳动心脏供体的心脏显示高能磷酸盐水平增加，心肌细胞活力、线粒体膜极化和结构蛋白得到保护。同样，在Somah中短期保存期间，冠状动脉内皮组织和功能、钙动员和一氧化氮生成也得到良好维持。
目前临床使用的Celsior保存溶液导致心肌细胞和内皮细胞活力大幅下降，而新设计的Somah溶液在器官保存期间保护了心肌细胞和内皮的完整性及功能。使用Somah作为保存介质可能会优化移植后移植物功能和患者长期生存率。
