Pickard, JM;
Burke, N;
Davidson, SM;
Yellon, DM;
(2017)
Intrinsic cardiac ganglia and acetylcholine are important in the mechanism of ischaemic preconditioning.
Basic Research in Cardiology
, 112
(2)
, Article 11. 10.1007/s00395-017-0601-x.
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Abstract
This study aimed to investigate the role of the intrinsic cardiac nervous system in the mechanism of classical myocardial ischaemic preconditioning (IPC). Isolated perfused rat hearts were subjected to 35-min regional ischaemia and 60-min reperfusion. IPC was induced as three cycles of 5-min global ischaemia-reperfusion, and provided significant reduction in infarct size (IS/AAR = 14 ± 2% vs control IS/AAR = 48 ± 3%, p < 0.05). Treatment with the ganglionic antagonist, hexamethonium (50 μM), blocked IPC protection (IS/AAR = 37 ± 7%, p < 0.05 vs IPC). Moreover, the muscarinic antagonist, atropine (100 nM), also abrogated IPC-mediated protection (IS/AAR = 40 ± 3%, p < 0.05 vs IPC). This indicates that intrinsic cardiac ganglia remain intact in the Langendorff preparation and are important in the mechanism of IPC. In a second group of experiments, coronary effluent collected following IPC, from ex vivo perfused rat hearts, provided significant cardioprotection when perfused through a naïve isolated rat heart prior to induction of regional ischaemia-reperfusion injury (IRI) (IS/ARR = 19 ± 2, p < 0.05 vs control effluent). This protection was also abrogated by treating the naïve heart with hexamethonium, indicating the humoral trigger of IPC induces protection via an intrinsic neuronal mechanism (IS/AAR = 46 ± 5%, p < 0.05 vs IPC effluent). In addition, a large release in ACh was observed in coronary effluent was observed following IPC (IPCeff = 0.36 ± 0.03 μM vs C eff = 0.04 ± 0.04 μM, n = 4, p < 0.001). Interestingly, however, IPC effluent was not able to significantly protect isolated cardiomyocytes from simulated ischaemia-reperfusion injury (cell death = 45 ± 6%, p = 0.09 vs control effluent). In conclusion, IPC involves activation of the intrinsic cardiac nervous system, leading to release of ACh in the ventricles and induction of protection via activation of muscarinic receptors.
| Type: | Article |
|---|---|
| Title: | Intrinsic cardiac ganglia and acetylcholine are important in the mechanism of ischaemic preconditioning |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00395-017-0601-x |
| Publisher version: | http://dx.doi.org/10.1007/s00395-017-0601-x |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2017. Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
| Keywords: | Intrinsic cardiac nervous system, Ischaemic preconditioning, Myocardial infarction |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1538612 |
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