Adenosine injection prior to cardioplegia enhances preservation of senescent hearts in rat heterotopic heart transplantation
Adenosine injection prior to cardioplegia enhances preservation of senescent hearts in rat heterotopic heart transplantation
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DOI：
10.1093/ejcts/ezs509
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发表时间：
2013-06-01
影响因子：
3.4
通讯作者：
Toyoda, Yoshiya
中科院分区：
文献类型：
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作者：
Lim, Sang Hyun;Lee, Sungsoo;Toyoda, Yoshiya
高龄供者是移植物衰竭的危险因素之一，也是心脏移植术后早期死亡的主要原因。更好的心肌保存方法应能减少移植物衰竭。这项研究的目的是确定腺苷是否可以增强心脏截瘫保护，在使用老年供者的心脏移植过程中增强心肌保存。我们采用大鼠异位心脏移植模型，以至少60周龄的Lewis大鼠为供体。在心脏停跳前注射生理盐水（对照）或腺苷（0.1或0.2 mg/kg），用冷Celsior灌注，心脏在Celsior中4℃保存6 h，移植到12-16周龄的同基因受者体内，再灌注3 h后采集血液和组织。与对照组相比，大剂量注射腺苷导致Celsior灌注后机械骤停更快，再灌注后恢复更快。血清肌钙蛋白I和肌酸磷酸激酶水平显示，腺苷治疗显著减轻心肌损伤。炎症细胞因子的mrna在对照移植物中显著增加，但在腺苷处理的移植物中上调较少。用腺苷处理的移植物也表现出更少的线粒体损伤，更少的浸润细胞和更高的三磷酸腺苷含量。心脏骤停灌注前注射腺苷可显著降低老年供体心脏移植物的冷缺血/再灌注损伤，提高再灌注后细胞能量的储存。这种采购方案在临床上可能是可行的，应在临床环境中加以考虑，特别是对老年献血者。
Advanced donor age is one of the risk factors for graft failure and is the leading cause of early death after heart transplantation. Better myocardial preservation methods should reduce graft failure. The purpose of this study was to determine if adenosine, which is known to enhance cardioplegic protection, enhances myocardial preservation during heart transplantation using older donors.We used a rat heterotopic heart transplantation model with Lewis rats that were at least 60 weeks old as donors. We injected saline (control) or adenosine (0.1 or 0.2 mg/kg) before cardioplegia, perfused with cold Celsior and stored the hearts in Celsior for 6 h at 4 degrees C. The grafts were transplanted into syngenic, 12-16-week old recipients, and blood and tissue were collected 3 h after reperfusion.Bolus injection of adenosine led to faster mechanical arrest after perfusion with Celsior and faster reanimation after reperfusion compared with controls. Adenosine treatment significantly reduced myocardial injury, as indicated by serum troponin I and creatine phosphokinase levels. The mRNAs for inflammatory cytokines were markedly increased in the control grafts, but were less upregulated in the grafts treated with adenosine. The grafts treated with adenosine also exhibited less mitochondrial damage, fewer infiltrating cells and a higher adenosine triphosphate content.Adenosine injection prior to perfusion of cardioplegia significantly reduced cold ischaemia/reperfusion injury in cardiac grafts from older donors and improved the stores of cellular energy after reperfusion. This procurement protocol may be clinically feasible and should be considered in the clinical setting, particularly for older donors.