Protective effect and mechanism of low P50 haemoglobin oxygen carrier on isolated rat heart

The protection of the isolated heart is very important in heart transplantation surgery, meanwhile, the ischaemia/reperfusion (I/R) of the isolated heart is the main cause of its damage. A timely supply of oxygen can significantly improve the prevention of myocardial ischaemia, however, the cardioprotective solution does not have an oxygen supply function. Haemoglobin Based on Oxygen Carriers (HBOCs) is a kind of nano-oxygen drug, which can effectively and timely supply oxygen to hypoxic organs and tissues. However, the oxygen-carrying and releasing capacity (P50) is different with different HBOCs. The aim of our study was to investigate whether STS (a kind of cardioprotective solution, St Thomas Solution) +different P50 HBOCs provide superior myocardial protection and decrease myocardial injury compared to only STS in rats Langendorff isolated heart perfusion model. The results showed that STS + HBOCs can improve cardiac function at 37 °C for 35 min and 120 min, and reduce myocardial infarctions, pathological changes, and apoptosis of cardiomyocytes, and the STS + low P50 HBOCs is more effective than the other two higher P50 HBOCs. We further demonstrated the outstanding protective effect of STS + low P50 HBOCs on cardiac function, reducing myocardial infarctions and apoptosis of cardiomyocytes in rat Langendorff isolated heart perfusion model.

离体心脏保护在心脏移植手术中至关重要，而离体心脏的缺血再灌注（ischaemia/reperfusion, I/R）损伤是引发其损伤的主要原因。及时供氧可显著改善心肌缺血的预防效果，但现有心肌保护液并不具备供氧功能。血红蛋白基氧载体（Haemoglobin Based on Oxygen Carriers, HBOCs）属于一类纳米氧载体药物，可高效、及时地为缺氧器官及组织供给氧气。不过，不同HBOCs的氧结合释放能力（P50）存在差异。本研究旨在探究：在大鼠Langendorff离体心脏灌注模型中，相较于单纯使用心肌保护液St Thomas Solution（简称STS），采用STS联合不同P50值HBOCs的方案是否能为心肌提供更优异的保护效果，并减轻心肌损伤。实验结果表明，在37℃条件下，联合HBOCs的STS可在灌注35分钟及120分钟时改善心脏功能，同时减少心肌梗死面积、病理损伤及心肌细胞凋亡；其中，联合低P50值HBOCs的STS效果优于另外两种高P50值HBOCs组。本研究进一步证实，在大鼠Langendorff离体心脏灌注模型中，联合低P50值HBOCs的STS对心脏功能具有显著保护作用，可有效减轻心肌梗死与心肌细胞凋亡情况。