Modulation of Mitochondrial Respiration During Early Reperfusion Reduces Cardiac Injury in Donation After Circulatory Death Hearts.
Modulation of Mitochondrial Respiration During Early Reperfusion Reduces Cardiac Injury in Donation After Circulatory Death Hearts.
复制标题
早期再灌流期间线粒体呼吸的调节可减少循环死亡心脏供体心脏的损伤。
DOI：
10.1097/fjc.0000000000001290
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发表时间：
2022-07-01
影响因子：
3
通讯作者：
Quader, Mohammed
中科院分区：
文献类型：
--
作者：
Akande, Oluwatoyin;Chen, Qun;Cholyway, Renee;Toldo, Stefano;Lesnefsky, Edward J.;Quader, Mohammed
关键词：
循环死亡后捐献（DCD）供体是心脏移植的潜在来源。DCD过程具有主要通过线粒体介导的不可避免的缺血和再灌注（I/R）损伤，这限制了心脏移植的常规利用。异戊巴比妥（AMO）是一种电子传递链的瞬时抑制剂，已知可减少离体I/R后的心脏损伤。我们研究了再灌注期间AMO治疗是否可以减少DCD心脏的损伤。在再灌注的前5分钟，用AMO或载体处理经受25分钟体内缺血的Sprague道利大鼠心脏（DCD心脏）或对照跳动供体（CBD）心脏，随后用Krebs-Henseleit缓冲液再灌注55分钟（用于线粒体分离）或85分钟（用于梗塞大小测定）。与溶剂相比，AMO处理导致梗死面积减少（25.2 ± 1.5% vs. 31.5 ± 1.5%; p≤0.05）和肌钙蛋白I释放减少（4.5 ± 0.05 ng/ml vs. 9.3 ± 0.24 ng/ml，p≤0.05）。AMO处理降低了两个肌膜下线粒体（SSM）中谷氨酸作为复合物I底物的H2 O2产生（37± 3.7 pmol/mg/min vs. 56.9 ± 4.1 pmol/mg/min; p≤0.05）和原纤维间线粒体（IFM）（31.8 ± 2.8 pmol/mg/min vs. 46±4.8 pmol/mg/min; p≤0.05），并改善SSM中的钙潴留能力（CRC）（360 ±17.2 nmol/mg vs. 277 ± 13 nmol/mg; p≤0.05）和IFM（483 ± 20 nmol/mg vs. 377± 19 nmol/mg; p≤0.05）。SSM和IFM保留更多的细胞色素c与AMO治疗相比，车辆。总之，短暂抑制线粒体呼吸在再灌注期间使用异戊巴比妥是一种有前途的方法，以减少损伤的DCD心脏。
Donation after circulatory death (DCD) donors are a potential source for heart transplantation. The DCD process has unavoidable ischemia and reperfusion (I/R) injury, primarily mediated through mitochondria, which limits routine utilization of hearts for transplantation. Amobarbital (AMO), a transient inhibitor of the electron transport chain, is known to decrease cardiac injury following ex-vivo I/R. We studied whether AMO treatment during reperfusion can decrease injury in DCD hearts. Sprague Dawley rat hearts subjected to 25 minutes of in-vivo ischemia (DCD hearts), or control beating donor (CBD) hearts, were treated with AMO or vehicle for the first 5 minutes of reperfusion, followed by Krebs-Henseleit buffer reperfusion for 55 minutes (for mitochondrial isolation) or 85 minutes (for infarct size determination). Compared to vehicle, AMO treatment led to decreased infarct size (25.2 ± 1.5% vs. 31.5 ± 1.5%; p≤0.05), and troponin I release (4.5 ± 0.05 ng/ml vs. 9.3 ± 0.24 ng/ml, p≤0.05). AMO treatment decreased H2O2 generation with glutamate as complex I substrate in both subsarcolemmal mitochondria (SSM) (37± 3.7 pmol/mg/min vs. 56.9 ± 4.1 pmol/mg/min; p≤0.05), and interfibrillar mitochondria (IFM) (31.8 ± 2.8 pmol/mg/min vs. 46±4.8 pmol/mg/min; p≤0.05), and improved calcium retention capacity (CRC) in SSM (360 ±17.2 nmol/mg vs. 277 ± 13nmol/mg; p≤0.05), and IFM (483 ± 20nmol/mg vs. 377± 19 nmol/mg; p≤0.05) compared to vehicle treatment. SSM and IFM retained more cytochrome c with AMO treatment compared to vehicle. In conclusion, brief inhibition of mitochondrial respiration during reperfusion using amobarbital is a promising approach to decrease injury in DCD hearts.
影响因子：
3.7
作者：
Quader M;Cholyway R;Wickramaratne N;Akande O;Mangino M;Mezzaroma E;Mauro AG;Chen Q;Kantlis A;Toldo S
通讯作者：
Toldo S
影响因子：
3.7
作者：
Yang M;Stowe DF;Udoh KB;Heisner JS;Camara AK
通讯作者：
Camara AK