Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?

Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?

To study the impact of 3 day exposure to atorvastatin 80mg on Annexin A5 targeting after ischemic exercise in the non-dominant forearm.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (also known as statins) have been found to reduce cardiovascular events. This protective effect has been traditionally explained by lowering plasma cholesterol and subsequent reduced progression of atherosclerosis. However in animal experiments statins have also shown the ability to induce pharmacologic preconditioning and thereby reduce infarct size. This effect contributes to the beneficial effect of statins on reducing of cardiovascular events. In order to differentiate between these two mechanisms of protection we will study the effect of atorvastatin on ischemia reperfusion damage after a short exposure to atorvastatin, before the lipid lowering effect of atorvastatin becomes apparent.

Inclusion Criteria:

• Male
• Age 18-50 years
• Informed consent
• Physical able to perform ischemic exercise

Exclusion Criteria:

• History of any cardiovascular disease
• Hypertension (in supine position: systole > 140 mmHg, diastole > 90 mmHg)
• Diabetes mellitus (fasting glucose > 7.0 mmol/L or random glucose > 11.0 mmol/L)
• Hyperlipidaemia (fasting total cholesterol > 5.5 mmol/l)
• Alanine-Amino-Transferase (ALAT) >90 U/L
• Creatinine Kinase (CK) >440 U/L
• Drug or alcohol abuse
• Concommitant chronic use of medication
• Administration of radioactivity in research setting during the last 5 years
• Participation to any drug-investigation during the previous 60 days as checked with VIP check according to CRCN standard procedures