3',4'-Dihydroxyflavonol improves post-ischaemic coronary endothelial function following 7 days reperfusion in sheep

Journal article


Wang, Sheng, Thomas, Colleen J., Dusting, Gregory, Woodman, Owen L. and May, Clive N.. (2009). 3',4'-Dihydroxyflavonol improves post-ischaemic coronary endothelial function following 7 days reperfusion in sheep. European Journal of Pharmacology. 624(1-3), pp. 31 - 37. https://doi.org/10.1016/j.ejphar.2009.10.001
AuthorsWang, Sheng, Thomas, Colleen J., Dusting, Gregory, Woodman, Owen L. and May, Clive N.
Abstract

3′,4′-dihydroxyflavonol (DiOHF) is a potent antioxidant that reduces infarct size following myocardial ischaemia–reperfusion. Since oxidative stress induced by myocardial ischaemia–reperfusion impairs endothelium-dependent vasodilatation, we investigated whether DiOHF preserved coronary endothelial function following ischemia–reperfusion. One week after surgery conscious, instrumented sheep were subjected to 1 h of myocardial ischaemia followed by 7 days reperfusion. Immediately before reperfusion, sheep were injected with DiOHF (2 mg/kg iv, n = 4) or vehicle (dimethyl sulphoxide, n = 4). Coronary vascular responses to the endothelium-dependent vasodilator acetylcholine (ACh, 0.05–10.0 µg/kg/min iv), sodium nitroprusside and phenylephrine were determined. After ischaemia–reperfusion, dP/dtmax decreased from 1511 ± 93 to 1094 ± 53 mmHg/s, P < 0.05) at 24 h in the vehicle group, but by 7 days had returned towards baseline (1347 ± 91 mm Hg/s). DiOHF prevented the fall in dP/dtmax. Coronary conductance (CC) was increased (+ 34 ± 4%) by 10 µg/kg ACh given before ischaemia, but this vasodilatation was significantly reduced after 24 h and 7 days of reperfusion (+ 7 ± 2%, + 15 ± 2%, respectively, both P < 0.05). DiOHF partially preserved the coronary vasodilator response to ACh after 24 h reperfusion (basal 37 ± 7%, 24 h 18 ± 5%), and after 7 days reperfusion the response had recovered (31 ± 7%). DiOHF significantly decreased infarct size, expressed as a percentage of area-at-risk, by 40% after 7 days reperfusion (vehicle 80 ± 7%, DiOHF 46 ± 11%, P < 0.05). A single administration of DiOHF, during ischaemia and just prior to reperfusion, reduced infarct size, preserved ventricular contractility and caused a sustained protection against coronary endothelial dysfunction, with all these beneficial actions being preserved for 7 days reperfusion.

Keywordsendothelial dysfunction; myocardial ischaemia–reperfusion injury; flavonol; antioxidant
Year2009
JournalEuropean Journal of Pharmacology
Journal citation624 (1-3), pp. 31 - 37
PublisherElsevier
ISSN0014-2999
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ejphar.2009.10.001
Page range31 - 37
Research GroupSports Performance, Recovery, Injury and New Technologies (SPRINT) Research Centre
Place of publicationThe Netherlands
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