Cardiothoracic Surgery Unit, The Alfred Hospital, Melbourne, Australia; Department of Surgery, Monash University, Melbourne, Australia.
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia; The Alfred Hospital, Melbourne, Australia.
Transplant Proc. 2021 Mar;53(2):612-619. doi: 10.1016/j.transproceed.2020.10.001. Epub 2020 Dec 2.
Use of donation after circulatory death (DCD) hearts is becoming more prevalent in cardiac transplantation. However, there is no standardized approach to myocardial preservation, and little data exists on ultrastructural changes in DCD hearts. We have previously identified increased proapoptotic and proinflammatory activity in brain dead donor (BDD) hearts that subsequently exhibit primary graft failure and lower levels in DCD left atrial tissue. This study further investigates these markers and correlates them with cardiac function in DCD hearts.
This prospective study used donor hearts deemed unsuitable for transplant after gaining institutional ethics approval; 11 human hearts were obtained from 5 DCD donors and 6 BDDs. All hearts were preserved by continuous microperfusion for 4 hours with a cold crystalloid solution and then were evaluated on a blood perfusion bench rig. After 4 hours perfusion and working assessment, tissues from all cardiac chambers were stored for later messenger RNA (mRNA) analysis for proapoptotic and proinflammatory markers.
Significantly raised levels of caspase-1, BNIP3, and NADPH oxidase mRNA expression were identified in cardiac chambers from BDD hearts compared to DCD hearts, and these differences were exaggerated in older donors. In the pooled analysis, lower expression of caspase-1, NF-κB1, and BNIP3 mRNA correlated with developed pressure at 1 hour after reperfusion in the right ventricle, but not the left.
Compared to BDD hearts, DCD hearts exhibit less stimulation of proapoptotic cascades and reactive oxygen species, potentially reducing their susceptibility to ischemic reperfusion injury.
在心脏移植中，使用循环死亡后捐献（DCD）心脏的情况越来越普遍。然而，目前还没有标准化的心肌保存方法，DCD 心脏的超微结构变化数据也很少。我们之前已经发现脑死亡供体（BDD）心脏中的促凋亡和促炎活性增加，随后会出现原发性移植物衰竭和 DCD 左心房组织中的水平降低。本研究进一步研究了这些标志物，并将其与 DCD 心脏的心脏功能相关联。
这项前瞻性研究使用了获得机构伦理批准后被认为不适合移植的供体心脏；从 5 名 DCD 供体和 6 名 BDD 中获得了 11 个人心脏。所有心脏均通过连续微灌注用冷晶体溶液保存 4 小时，然后在血液灌注台架上进行评估。灌注和工作评估 4 小时后，从所有心腔的组织中提取信使 RNA（mRNA）进行促凋亡和促炎标志物分析。
与 DCD 心脏相比，BDD 心脏的心腔中 caspase-1、BNIP3 和 NADPH 氧化酶 mRNA 表达水平显著升高，并且这种差异在较老的供体中更为明显。在汇总分析中，caspase-1、NF-κB1 和 BNIP3 mRNA 的表达水平较低与右心室再灌注后 1 小时的发展压力相关，但与左心室无关。
与 BDD 心脏相比，DCD 心脏的促凋亡级联和活性氧的刺激较少，可能降低其对缺血再灌注损伤的易感性。
