Gao, Ling and Hicks, Mark and Villanueva, Jeanette E and Doyle, Aoife and Chew, Hong C and Qui, Min Ru and Jabbour, Andrew and Dhital, Kumud K and Macdonald, Peter S (2019) Cyclosporine A as a cardioprotective agent during donor heart retrieval, storage or transportation - benefits and limitations. Transplantation, ePub. p. 1. ISSN 0041-1337 (Not OA)
Full text not available from this repository.Abstract
BACKGROUND:
Storage of donor hearts in cardioplegic solutions supplemented with conditioning agents activating endogenous mitochondrial protective signaling enhanced their post-reperfusion recovery. The present study investigates the role of timing and duration of cardiac exposure to cyclosporine A, another putative mitochondrial protectant, on cardiac functional recovery and potential mechanisms of CsA action in an isolated working rat heart model of donor heart retrieval and storage.
METHODS:
After measurement of baseline function, hearts were arrested and stored for 6h at 4°C in either Celsior® alone or Celsior®+CsA (0.2µM), then reperfused for 45min in Krebs solution, when functional recovery was assessed. Two additional groups of Celsior®-alone stored hearts were exposed to 0.2µM CsA for the initial 15min (non-working period) or the full 45min period of reperfusion. Coronary effluent was collected pre- and post-storage for assessment of LDH release. Tissue samples were collected at the end of each study for immunoblotting and histological studies.
RESULTS:
CsA supplementation during cold storage or the first 15min reperfusion significantly improved functional recovery and significantly increased phospho-AMPKαThr172 and phospho-ULK-1Ser757. Hearts exposed to CsA for 45min post-reperfusion recovered poorly with no phospho-AMPKα activation, decreased phospho-eNOSSer633 and mitochondrial cyctochrome c content with increased LDH release.
CONCLUSIONS:
Inclusion of CsA during cold storage is cardioprotective. Effects of CsA addition to the perfusate during reperfusion was time dependent, with benefits at 15 but not 45 min of reperfusion. The toxic effect with the presence of CsA for the full 45min reperfusion is associated with impaired mitochondrial integrity and decreased eNOS phosphorylation.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 11 Mar 2019 04:48 |
| Last Modified: | 11 Mar 2019 04:55 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/814 |
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