Teh Elaine S, Zal Franck, Polard Valérie, Menasché Philippe, Chambers David J
a Cardiac Surgical Research/Cardiothoracic Surgery , the Rayne Institute (King's College London), Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital , London , UK.
b Biotechnopôle , Hemarina SA, Aéropôle Centre , Morlaix , France.
Artif Cells Nanomed Biotechnol. 2017 Jun;45(4):717-722. doi: 10.1080/21691401.2016.1265974. Epub 2017 Jan 12.
Prior to heart transplantation, static storage of donor hearts is currently limited to 4-5 h, despite profound hypothermia (4-8 °C). Because heart transplantation is an emergency procedure, improved protection to extend safe storage duration would be advantageous. We investigated whether the naturally respiratory pigment HEMOlife, which is effective at hypothermia for the passive release of oxygen via oxygen gradient, could improve long-term preservation.
Isolated Langendorff-perfused rat hearts (n = 12/group) were equilibrated (20 min) and function (left ventricular developed pressure: LVDP) measured by intraventricular balloon before arrest with cold (7.5 °C) Celsior solution, either alone (control) or with the addition of HEMOlife (Hemarina SA, Morlaix, France) at 1 g/L. Cold storage lasted 8 h prior to reperfusion (60 min) and recovery (as % of pre-ischemic function) was assessed. Hearts (minced and homogenized) were also assessed by TTC staining as a measure of viability and two hearts from each group were sliced and assessed by TTC staining for infarct size. Values are expressed as mean ± standard error of mean and analyzed by Student's t-test.
Hearts recovered rapidly in both groups to a plateau by 20 min of reperfusion; control and HEMOlife final recovery (60 min) was 45 ± 2% and 57 ± 1% (P < 0.05) respectively. Left ventricular end-diastolic pressure recovered to a similar extent in both groups (between 31 to 35 mmHg), as did heart rate (final recovery between 84 to 89% pre-ischemic value); however, coronary flow was significantly (P < 0.05) higher in HEMOlife group (7.5 ± 0.7 ml/min) compared to control (5.4 ± 0.4 ml/min). Viability and infarct size measurements were similar between groups.
The addition of the natural oxygen releasing pigment HEMOlife to Celsior preservation solution significantly improved post-ischemic recovery of heart function. This additive may have major therapeutic potential for clinical heart transplantation.
在心脏移植之前,尽管采用深度低温(4 - 8°C),供体心脏的静态保存目前仍限于4 - 5小时。由于心脏移植是一种紧急手术,改善保护措施以延长安全保存时间将是有益的。我们研究了天然呼吸色素HEMOlife(在低温下通过氧梯度被动释放氧气有效)是否能改善长期保存效果。
将离体Langendorff灌注大鼠心脏(每组n = 12)平衡(20分钟),并用室内球囊测量功能(左心室舒张末压:LVDP),然后用冷(7.5°C)Celsior溶液停搏,单独使用(对照组)或添加1 g/L的HEMOlife(法国莫尔莱的Hemarina SA公司)。冷保存持续8小时,然后进行再灌注(60分钟),并评估恢复情况(作为缺血前功能的百分比)。还通过TTC染色评估心脏(切碎并匀浆)的活力,每组取两颗心脏切片并用TTC染色评估梗死面积。数值以平均值±平均标准误差表示,并通过学生t检验进行分析。
两组心脏在再灌注20分钟时均迅速恢复至平台期;对照组和HEMOlife组最终恢复率(60分钟)分别为45±2%和57±1%(P < 0.05)。两组左心室舒张末压恢复程度相似(在31至35 mmHg之间),心率也是如此(最终恢复至缺血前值的84至89%);然而,与对照组(5.4±0.4 ml/min)相比,HEMOlife组的冠状动脉血流量显著更高(P < 0.05)(7.5±0.7 ml/min)。两组之间的活力和梗死面积测量结果相似。
在Celsior保存液中添加天然氧释放色素HEMOlife可显著改善缺血后心脏功能的恢复。这种添加剂可能对临床心脏移植具有重大治疗潜力。