Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury

Overview

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.