Ischemia-Reperfusion Injury, Myocardial Infarction
Conditions
Keywords
Apoptosis, Annexin, Hypoxia, Ischemia-Reperfusion Injury
Brief summary
Rationale: The investigators hypothesize that EPO protects against apoptosis after acute ischemia in man and that it is detectable using the annexin-A5 model. Objective: Does infusion of a single dose of Epoetin Alfa, a short-acting EPO, protect against apoptosis in man after acute ischemia? Study design: A double blinded randomised cross-over study. Study population: 12 Healthy male volunteers, between 18 and 40 years old. Intervention: All 12 volunteers will receive a single dose of EPO and placebo in a randomized order. A six week wash-out period is obtained in order to avoid interference of both treatments. Main study parameters/endpoints: The percentage of difference between radioactivity (quantified as counts per pixel) of the experimental and control thenar muscle at one and four hours after reperfusion.
Interventions
DRUGEpoetin alpha
The dosage (60.000 I/U Epoetin alpha) will be diluted in 10 ml of 0.9% sodium chloride solution and injected in a single dose intravenously in the dominant forearm (the non-dominant forearm will be used as ischemic model).
DRUGNaCl
0.9% sodium chloride solution as placebo dosage is 10 ml, which will be administered in the same manner as the interventional medicinal product.
Sponsors
Radboud University Medical Center
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers between 18 and 40 years of age * male * Volunteers are not allowed smoking 24 hours before the start of the experiment
Exclusion criteria
* Female * Hypertension (SBP \>140 mmHg, DBP \>90 mmHg) * Diabetes Mellitus (DM) (fasting glc \>6.9 mmol/l, glc \>11.0 mmol/l) * Hypercholesterolemia * Renal dysfunction (eGFR \< 60 ml/min, calculated using MDRD formula) * Any known hypersensitivity/allergic reaction to one of the constituents of Epoetin Alfa * A history of use of any form of EPO * Any current medication use * Cardiovascular disease in medical history * Smoking less than 24 hours prior to Epoetin alpha infusion * Participation in research in the last 5 years in which any form of radioactivity was used * No participation in any research trial in the last 30 days or 5 times the half-life of the used substance
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The percentage of difference between radioactivity (quantified as counts per pixel) of the predefined area of interest of the experimental and control thenar muscle at one and four hours after reperfusion. | 4 hours |
Secondary
| Measure | Time frame |
|---|---|
| DNA polymorphisms affecting HO-1 and AMP-deaminase activity is assessed by DNA analysis. | 4 hours |
| The effect of EPO treatment on heme oxygenase activity as measured in blood and as CO concentration in exhaled air. | 4 hours |
| Maximal voluntary contraction and duration of the exercise during ischemia. | 10 minutes |
Countries
Netherlands
Contacts
Primary ContactW. T. Ruifrok, MD
Backup ContactR. A. de Boer, MD, PhD
Outcome results
None listed