Ischemia Reperfusion Injury
Conditions
Keywords
Rosuvastatin, Caffeine, Ischemia, Reperfusion
Brief summary
Does caffeine reduce rosuvastatin induced protection against ischemia reperfusion injury?
Detailed description
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.
Interventions
DRUGRosuvastatin
7 day treatment rosuvastatin 20mg
Sponsors
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The targeting of Technetium 99 labeled Annexin A5 is recorded with a gamma camera as a endpoint measure of ischemia-reperfusion damage. | 60 and 240 minutes after ischemic exercise |
Secondary
| Measure | Time frame |
|---|---|
| Workload (product of 50% of the maximum forearm force and duration of the ischemic exercise) | during 10 minutes of ischemic exercise |
| The effect of one-week treatment of rosuvastatin 20mg once daily on lipid spectrum. | before and after 7day treatment |
| The caffeine serum concentration after 24 hour abstinence . | morning after 24 hours abstinence of caffeine |
Countries
Netherlands
Outcome results
None listed