Heart Disease, Vascular Disease
Conditions
Keywords
Astressin 2B, Forearm blood flow, vascular, plethysmography, heart failure
Brief summary
Impairment of the heart's pumping capacity (heart failure) remains a major clinical problem with a poor prognosis and the search for novel treatments remains an important area of research. Urocortins are proteins that appear to increase blood flow and heart pumping activity. There has been particular interest in the role of Urocortins 2 & 3 (subtypes of Urocortins) in heart failure. In this study, we will examine the effects and mechanisms of Urocortins 2 & 3 and the Corticotrophin Releasing Hormone Receptor Type 2 (CRH-R2) receptor (through which urocortins act) on forearm blood flow and release of natural blood clot dissolving factors in the forearm circulation of healthy volunteers. In this study, we will look at the role of the lining of the blood vessel (endothelium) in response to urocortin types 2 and 3. We hypothesise that urocortins 2 & 3 act via the endothelium to cause dilatation of the blood vessels and release of tissue-plasminogen activating factor (blood clot dissolving factor). We also hypothesise that urocortins have a role in maintaining the normal baseline level of blood flow in forearm arteries. In addition to the above, we will also look at the effect of temporarily blocking the effect of urocortins, using a specially designed blocker drug (Astressin 2B). Utilising the well-established technique of 'forearm venous occlusion plethysmography', we will be able to focus on the local effects of urocortins on arterial blood flow in forearm vessels, without affecting this system in the body as a whole.
Interventions
DRUGAstressin 2B
After an initial saline washout, increasing doses of Astressin 2B (at 0.032, 0.32, 3.2, 32, 320 and 3200 pmol/min) will be infused, for 10 minutes at each dose,intra arterially using forearm venous occlusion plethysmography. Forearm blood flow will be measured with each incremental dose of Astressin 2B.
Sponsors
University of Edinburgh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male volunteers between 18 - 65 years (inclusive)
Exclusion criteria
* Lack of informed consent * Age \<18 years \> 65 years * Current involvement in a clinical trial * Severe or significant co-morbidity including bleeding diathesis, renal or hepatic failure * Smoker * History of anaemia * Recent infective/inflammatory condition * Recent blood donation (prior 3 months) * Positive baseline urine test for drugs of abuse (including cannabinoids, benzodiazepines, opiates, cocaine and amphetamines)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in forearm blood flow | 3 hours | Absolute change in forearm blood flow with respect to baseline forearm blood flow resulting from infusion of the study drugs, using forearm venous occlusion plethysmography |
Secondary
| Measure | Time frame |
|---|---|
| Principle safety assessment, heart rate and blood pressure | 3 hours |
Countries
United Kingdom
Outcome results
None listed