期刊
HEART LUNG AND CIRCULATION
卷 24, 期 3, 页码 306-318出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.hlc.2014.10.001
关键词
Donor heart; Ischaemia reperfusion injury; Pharmacological conditioning; Mitochondria; Sodium hydrogen exchange inhibitor; Glyceryl trinitrate
资金
- National Heart Foundation of Australia [G 04S 1619, G 07S 3044]
- National Health & Medical Research Council [573732]
- Gastroenterological Society of Australia
Background Storage of donor hearts in cardioplegic solutions supplemented with agents that mimic the ischaemic preconditioning response enhanced their post-reperfusion function. The present study examines the minimisation of cell death and activation of pro-survival signalling directed towards maintenance of mitochondrial homeostasis in hearts arrested and stored in two such agents, glyceryl-trinitrate, a nitric oxide donor and cariporide, (a sodium-hydrogen exchange inhibitor). Methods After baseline functional measurement, isolated working rat hearts were arrested and stored for 6 h at 4 degrees C in either Celsior (R), Celsior (R) containing 0.1 mg/ml glyceryl-trinitrate, 10 mu M cariporide or both agents. After reperfusion, function was remeasured. Hearts were then processed for immunoblotting or histology. Results Necrotic and apoptotic markers present in the Celsior1 group post-reperfusion were abolished by glyceryl-trinitrate, cariporide or both. Increased phosphorylation of ERK and Bcl2, after reperfusion in groups stored in glyceryl-trinitrate, cariporide or both along with increased phospho-STAT3 levels in the glyceryl-trinitrate/cariporide group correlated with functional recovery. Inhibition of STAT3 phosphorylation blocked recovery. No phospho-Akt increase was seen in any treatment. Conclusions Activation of signalling pathways that favour mitophagy activation (ERK and Bcl2 phosphorylation) and maintenance of mitochondrial transition pore closure after reperfusion (STAT3 and ERK phosphorylation) were crucial for functional recovery of the donor heart.
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