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3',4'-Dihydroxyflavonol improves post-ischaemic coronary endothelial function following 7days reperfusion in sheep.
MedLine Citation:
PMID:  19825372     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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 1h of myocardial ischaemia followed by 7 days reperfusion. Immediately before reperfusion, sheep were injected with DiOHF (2mg/kg iv, n=4) or vehicle (dimethyl sulphoxide, n=4). Coronary vascular responses to the endothelium-dependent vasodilator acetylcholine (ACh, 0.05-10.0 microg/kg/min iv), sodium nitroprusside and phenylephrine were determined. After ischaemia-reperfusion, dP/dt(max) decreased from 1511+/-93 to 1094+/-53 mmHg/s, P<0.05) at 24h in the vehicle group, but by 7 days had returned towards baseline (1347+/-91 mmHg/s). DiOHF prevented the fall in dP/dt(max). Coronary conductance (CC) was increased (+34+/-4%) by 10 microg/kg ACh given before ischaemia, but this vasodilatation was significantly reduced after 24h and 7 days of reperfusion (+7+/-2%, +15+/-2%, respectively, both P<0.05). DiOHF partially preserved the coronary vasodilator response to ACh after 24h reperfusion (basal 37+/-7%, 24h 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.
Authors:
Sheng Wang; Colleen J Thomas; Greg J Dusting; Owen L Woodman; Clive N May
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-13
Journal Detail:
Title:  European journal of pharmacology     Volume:  624     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  31-7     Citation Subset:  IM    
Affiliation:
Howard Florey Institute, University of Melbourne, Victoria 3010, Australia.
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