Cardiovascular Disease, Ischemia Reperfusion Injury
Conditions
Keywords
ischemia reperfusion injury, atorvastatine, preconditioning, cardiovascular disease
Brief summary
To study the impact of 3 day exposure to atorvastatin 80mg on Annexin A5 targeting after ischemic exercise in the non-dominant forearm.
Detailed description
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.
Interventions
DRUGatorvastatin
atorvastatine 80mg, during 3 days
Sponsors
Pfizer
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Annexin A 5 targeting in the non dominant thenar muscle after ischemic exercise, as a indicator for ischemia reperfusion injury. | 60 and 240 minutes after ischemic exercise |
Secondary
| Measure | Time frame |
|---|---|
| workload during ischemic exercise | workload during 10minutes of ischemic exercise |
| effect of 3-day treatment with atorvastatin 80mg daily on serum lipid levels | fasting lipid levels before and at first day after 3 day treatment with atorvastatin |
Countries
Netherlands
Outcome results
None listed