Blood poisoning sepsis
Conditions
Interventions
Subjects will be included in one of three different protocols:
1. In this arm, 2 subjects will be infused with 2.9 mg/kg bilirubin (diluted in
albumin 200 mg/ml).
2. Subjects in this group (n=10) wi
Sponsors
Universitair Medisch Centrum Sint Radboud
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: -Age >= 18 and
Exclusion criteria
Exclusion criteria: -Use of any medication or anti-oxidant vitamin supplements. -History of allergic reaction to albumin or any other drug used in the study. -Smoking. -Previous spontaneous vagal collapse. -History, signs or symptoms of cardiovascular disease. -(Family) history of myocardial infarction or stroke under the age of 65 years. -Cardiac conduction abnormalities on the ECG consisting of a 1st degree (or higher degree) atrioventricular block or a complex bundle branch block. - Hypertension (defined as a repeated measurement of RR systolic > 160 or RR diastolic > 90 mmHg). - Hypotension (defined as RR systolic 120 µmol/l). - Liver enzyme abnormalities or positive hepatitis B serology. - Subjects with a total bilirubin level above 15 µmol/L and a normal direct bilirubin level suggesting Gilbert Syndrome. - Positive HIV serology or any other obvious disease associated with immune deficiency. - Febrile illness in the week before the experiment. - Participation in a drug trial or donation of blood 3 months prior to the LPS challenge. - Inability to understand the nature and extent of the trial and the procedures required.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The main study parameter is the concentration of circulating cytokines at different time points following LPS administration in the absence or presence of hyperbilirubinemia. | — |
Secondary
| Measure | Time frame |
|---|---|
| - pro-anti oxidant balance during human endotoxemia in the absence or presence of hyperbilirubinemia - endothelial dysfunction during human endotoxemia in the absence or presence of hyperbilirubinemia as assessed by the measurement of the response to vasodilators acetylcholine and nitroglycerin. Furthermore, the release of vascular adhesion molecules indicating activation of the endothelium will be measured - subclinical renal damage known to occur during human endotoxemia in the absence or presence of hyperbilirubinemia - the interplay between HO-1, NO and bilirubin during human endotoxemia | — |
Countries
Netherlands
Outcome results
None listed