Reduction in Splanchnic Capacitance Contributes to Sympathetically Dependent Hypertension in Autonomic
Multiple System Atrophy, Orthostatic Hypotension, Supine Hypertension
About this trial
This is an interventional basic science trial for Multiple System Atrophy
Eligibility Criteria
Inclusion Criteria:
- Male and female subjects, age 40-80 years, with possible or probable Multiple System Atrophy, as defined by Consensus Criteria.
- Neurogenic orthostatic hypotension defined as a ≥30-mmHg decrease in systolic blood pressure within 3 minutes of standing associated with impaired autonomic reflexes determined by autonomic testing in the absence of other identifiable causes.
- Supine hypertension, defined as systolic blood pressure ≥150 mmHg measured on two separate occasions.
- Subjects able and willing to provide informed consent.
Exclusion Criteria:
- Pregnancy.
- Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathies, and autoimmune neuropathies
- History of known aortic aneurysms, thoracic, abdominal or pelvic surgery in the past 6 months
- Symptomatic abdominal or inguinal hernias
- Severe gastroesophageal reflux
- Recent fractures or fissures of ribs, thoracic or lumbar spine
- Medical devices implanted on the abdominal wall or abdomen that would interfere with the abdominal compression
- Intolerance to any increase in intra-abdominal pressure
- Clinically unstable coronary artery disease or major cardiovascular or neurological event in the past 6 months, and other factors which in the investigator's opinion would prevent the subject from completing the protocol including clinically significant abnormalities in clinical, mental or laboratory testing.
Sites / Locations
- Vanderbilt University Medical Center
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Trimethaphan
Placebo
The investigator will measure cardiac output by studying the air the participant breathes in and out. The participant will also wear a facemask to apply a low air pressure to the airway. After this, the trimethaphan infusion will begin with a small dose and the investigators increase at 1-2 minute intervals for up to five doses. The measurements will be collected again. Next, a standard blood pressure cuffs will be wrapped around the participant's abdomen. the cuff will inflate to apply pressure for 5 - 15 minutes.
The investigator will measure cardiac output by studying the air the participant breathes in and out. The participant will also wear a facemask to apply a low air pressure to the airway. After this, the placebo (saline) infusion will begin with a small dose and the investigators increase at 1-2 minute intervals for up to five doses. The measurements will be collected again. Next, a standard blood pressure cuffs will be wrapped around the participant's abdomen. the cuff will inflate to apply pressure for 5 - 15 minutes.