Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury
Status:
Completed
Trial end date:
2010-03-01
Target enrollment:
Participant gender:
Summary
Rationale:
Apart from their cholesterol lowering effects, statins have cholesterol-independent
pleiotropic actions, such as upregulation of 5'-ectonucleotidase and up-regulation of
NO-synthase that may increase tolerance against ischemia-reperfusion injury (IR-injury).
Several animal studies have shown reduction of IR-injury as a result of statin treatment in
both the heart and the kidney. Recently the investigators have shown, using Annexin A5
targeting after voluntary ischemic exercise to assess IR-injury, a protective effect of a 7
day oral rosuvastatin treatment. A three day treatment with atorvastatin however failed to
reduce annexin targeting.
Assessment of the flow mediated dilation of the brachial artery as measure of endothelial
(dys)function, is a validated model to research effects of possible protective strategies and
perform mechanistic experiments on IR-injury in humans in vivo.
The investigators hypothesize that pretreatment with statins can increase endothelial
tolerance against ischemia and reperfusion injury.
Objective:
To study the protective effect of pretreatment (both 3 day and 7 day) with rosuvastatin and
atorvastatin on flow mediated dilation after 15 minutes ischemia and 15 minutes reperfusion.
Study design: placebo-controlled randomised double-blind trial
Study population: Healthy volunteers, age 18-50
Intervention: Treatment with either rosuvastatin 20 mg, atorvastatin 80mg or placebo during
either 3 or 7 days
Main study parameters: Difference in flow mediated dilation before and after 15 minutes
ischemia.
Nature and extent of the burden and risks associated with participation, benefit and group
relatedness: Treatment with rosuvastatin or atorvastatin is not expected to harm the
volunteers. Most reported side effects of rosuvastatin and atorvastatin are gastro-intestinal
complains and myalgia. The volunteers will not benefit directly from participating in this
study.