Does Caffeine Reduce Rosuvastatin-Induced Protection Against Ischemia-Reperfusion Injury?

Rosuvastatin is a proven cholesterol lowering medicine, which hereby is assumed to achieve a reduction in cardiovascular events. Apart from it's cholesterol lowering action, rosuvastatin may also increase tolerance against ischemia-reperfusion injury. In dogs rosuvastatin increases the endogenous concentration of adenosine, by enhancing the activity of the enzyme ecto-5'-nucleotidase, which converts adenosine monophosphate into adenosine. We hypothesize that rosuvastatin increases tolerance against ischemia-reperfusion injury by induction of ecto-5'-nucleotidase and thereby increasing adenosine activity. This protective effect of rosuvastatin can be abrogated by using the adenosine receptor antagonist caffeine.

Inclusion criteria

• Male
• age between 18-50 yrs
• signed informed consent

Exclusion criteria

• Cardiovascular disease
• Hypertension (systole > 140 mmHg, diastole > 90 mmHg)
• Hypercholesterolemia (fasting total cholesterol > 6,0 mmol/l)
• Drug abuse
• Concomitant medication use
• Inability to perform the ischemic isometric muscle contraction
• Diabetes Mellitus (fasting glucose > 7.0 mmol/L or random glucose > 11.0 mmol/L)
• Alanine-Amino-Transferase (ALAT) >90U/L (more than twice the upper level of the normal range)
• Creatinine Kinase (CK) >340U/L (more than twice the upper level of the normal range)
• Participation in any trial concerning medicinal products during the last 60 days prior to this study.
• Participation in clinical trial involving