Endotoxin, Escherichia Coli, Regional Blood Flow, Retina
Conditions
Brief summary
Oxidative stress, which refers to cellular damage caused by reactive oxygen intermediates, has been implicated in many disease processes, especially age-related disorders. Many trials investigating use of antioxidants in protecting different tissues against oxidative stress have been conducted, but the results are ambiguous. Inflammation is generally associated with enhanced oxidative stress and widespread endothelial dysfunction. In the present study, the infusion of LPS, which is a cell wall component of Gram-negative bacteria and a major mediator in the pathogenesis of septic shock, will be used as a standardized experimental model of systemic inflammatory response in humans. The assessment of outcome parameters will include measurements of ocular blood flow, forearm blood flow and plasma concentration of cytokines. Measurements of ocular hemodynamics provide an unique chance to investigate local blood flow in humans non-invasively. Moreover, the retina is especially susceptible to oxidative stress because of its high consumption of oxygen, its high polyunsaturated fatty acid content, and its exposure to visible light. Evidence from literature clearly supports a role for oxidative stress in pathophysiology of several ocular diseases including diabetic retinopathy and age-related macular degeneration. To investigate the retinal vascular reactivity we will use systemic hyperoxia as a stimulus. The measurement of forearm blood flow will be use to assess endothelial function. The main study objective is to investigate the effect of oral vitamins and minerals supplementation on impaired retinal vascular reactivity after LPS administration.
Interventions
dose: 4 tablets daily for two weeks vitamin A 7160 IU, vitamin C 113mg, vitamin E 100IU, zinc 17.4mg, copper 0.4mg
DRUGEscherichia coli Endotoxin (LPS)
dose: 2 ng/kg (corresponding to 20 IU/kg), intravenous bolus over 5 minutes on both study days
DRUG100% O2
breathing for 30 minutes, 2 breathing periods on both study days
DRUGnitroglycerin
dose: 0,8 mg sublingual, applied during FMD measurements on both study days
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Men aged between 18 and 35 years, nonsmokers * Body mass index between 15th and 85th percentile * Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant * Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant * Normal ophthalmic findings, ametropia \< 3 Dpt
Exclusion criteria
* Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study * Treatment in the previous 3 weeks with any drug, vitamins and minerals supplements as well * Symptoms of a clinically relevant illness in the 3 weeks before the first study day * History of hypersensitivity to the trial drug or to drugs with a similar chemical structure * History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with, distribution, metabolism or excretion of study drugs * Blood donation during the previous 3 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Retinal blood flow | in total 8x on 2 study days |
Secondary
| Measure | Time frame |
|---|---|
| Choroidal blood flow | in total 4x on 2 study days |
| Flow mediated dilation (FMD) of brachial artery assessed with ultrasound | in total 4x on 2 study days |
| Blood pressure, heart rate | on 2 study days |
| Body temperature | on 2 study days |
| Concentration of cytokines in plasma | on 2 study days |
Countries
Austria
Outcome results
None listed