Details

Autor(en) / Beteiligte

• Kwan, Jair C., PhD
• Gao, Ling, PhD
• Macdonald, Peter S., MD, DSc
• Hicks, Mark, PhD

Titel

Cardio-protective Signalling by Glyceryl Trinitrate and Cariporide in a Model of Donor Heart Preservation

Ist Teil von

• Heart, lung & circulation, 2015-03, Vol.24 (3), p.306-318

Ort / Verlag

Australia: Elsevier B.V

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 °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. Results Necrotic 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. 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.