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Effect of Selective/Non-selective COX Inhibition on Rosuvastatin-Mediated Protection from Ischemia-reperfusion Induced Endothelial Dysfunction in the Human Forearm Vasculature

Statins can act as preconditioning agents against ischemia reperfusion (IR)-injury through a mechanism involving cyclooxygenase (COX)-2 and the upregulation of prostaglandin synthesis. The following study investigated the effect of selective and non-selective COX inhibition on rosuvastatin-mediated protection against IR-induced endothelial dysfunction in the human forearm vasculature. Healthy volunteers were randomized to drugs with different COX-inhibiting properties: 81mg aspirin (OD), 325mg aspirin (OD), 400mg ibuprofen (QID), 200mg celecoxib (BID) or placebo. A single dose of 40mg rosuvastatin was also administered 24-hours prior to IR. Endothelial function before and after IR was assessed by measuring flow-mediated dilation of the radial artery. Our results show that 81mg and 325mg aspirin (more COX-1 selective), 400mg ibuprofen (similar selectivity for COX-1/2) and 200mg celecoxib (COX-2 selective) all effectively abolished statin-mediated protection against IR-induced endothelial dysfunction in the forearm (2-way ANOVA, p<0.05). These findings indicate that even partial COX-2 inhibition is sufficient to attenuate statin-induced preconditioning.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/29586
Date25 August 2011
CreatorsKwong, Wilson
ContributorsParker, John
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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