None listed
Conditions
Brief summary
Cardiovascular disease is a leading cause of death and significant burden on our health system. Existing drug treatments remain less than ideal. We need additional effective strategies for management of these patients. Reducing sympathetic nerve firing directed at the heart, which may exacerbate heart damage and cause sudden death, is desirable following heart attacks. A family of hormones, the urocortins (Ucn), have been proposed as novel therapeutic agents in this setting. We propose to determine whether Ucn can also inhibit sympathetic nerve activity (measured in the leg) in 8 healthy male volunteers and 8 males with stable heart failure. Participants will receive in a random order either Ucn2 (25 ug over 60 min) or matching placebo infusions on 2 separate occasions separated by 8 weeks. Each study day will occur on the fourth day of identical and constant salt controlled diets. On the morning of each study day, subjects will positioned in a lazy-boy reclined chair where they will remain for the duration of the study. Microneurography needles will be inserted in the right superficial peroneal nerve in the lower leg. Blood pressure will be measured continuously throughtout the infusion. Nerve activity recordings and blood sampling will occur at 5-15 minute intervals from 30 minutes prior to infusion for 2 hours These studies should clarify the true therapeutic potential of Ucn in cardiovascular disease.
Interventions
We propose to determine whether Urocortin 2 (Ucn2) can inhibit sympathetic nerve activity (measured in the leg) in 8 healthy male volunteers and 8 males with stable heart failure.
Participants will receive in a random order either Ucn2 (25 ug ) or matching placebo infusions over 60minutes on 2 separate occasions separated by 8 weeks. Each study day will occur on the third day of identical and constant salt controlled diets (Sodium 120mmol/day, Potassium 100mmol/day for 2 days prior to the infus
We propose to determine whether Urocortin 2 (Ucn2) can inhibit sympathetic nerve activity (measured in the leg) in 8 healthy male volunteers and 8 males with stable heart failure. Participants will receive in a random order either Ucn2 (25 ug ) or matching placebo infusions over 60minutes on 2 separate occasions separated by 8 weeks. Each study day will occur on the third day of identical and constant salt controlled diets (Sodium 120mmol/day, Potassium 100mmol/day for 2 days prior to the infusion on Day 3. On the morning of each study day, subjects will positioned in a lazy-boy reclined chair where they will remain for the duration of the study. Microneurography needles will be inserted in the right superficial peroneal nerve in the lower leg. Blood pressure and nerve activity recordings will be measured continuously and blood sampling will occur at 15 minute intervals from 30 minutes prior to infusion to 2 hours after.
Sponsors
Health Research Council of New Zealand
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Diagnosis
Masking
Blinded (masking used)
Eligibility
Sex/Gender
Male
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Part 1 Inclusion: Absence of significant respiratory, liver or renal disease, or active malignancy. No drugs affecting haemodynamics or sympathetic nerve activity Part 2: Inclusion Stable left ventricular dysfunction with left ventricular ejection fraction <40% New York Heart Association (NYHA) class II or III symptoms Absence of significant respiratory, liver or renal disease, or active malignancy.
Exclusion criteria
Exclusion: peripheral neuropathy, atrial fibrillation, autonomic failure, chronic hypotension Inability to give informed consent
Outcome results
None listed