کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2917069 | 1175655 | 2015 | 13 صفحه PDF | دانلود رایگان |
BackgroundStorage 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).MethodsAfter baseline functional measurement, isolated working rat hearts were arrested and stored for 6 h at 4 °C in either Celsior®, Celsior® containing 0.1 mg/ml glyceryl-trinitrate, 10 μM cariporide or both agents. After reperfusion, function was remeasured. Hearts were then processed for immunoblotting or histology.ResultsNecrotic and apoptotic markers present in the Celsior® 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.ConclusionsActivation 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.
Journal: Heart, Lung and Circulation - Volume 24, Issue 3, March 2015, Pages 306–318