The Pathophysiology of Orthostatic Hypotension

Vanderbilt University Medical Center10 enrolled

Overview

The purpose of this study is to determine the cause of low blood pressure in selective patients who have problems with their involuntary (autonomic) nervous system. These patients frequently have had symptoms throughout their life, and their disorder might have a genetic basis. The biochemical, physiological and pharmacological procedures in this study should help us define the problem and perhaps lead to more effective treatment.

Study Type

INTERVENTIONAL

Allocation

Purpose

SCREENING

Masking

NONE

Enrollment

Conditions

Autonomic Nervous System Diseases Orthostatic Hypotension Dopamine Beta-Hydroxylase Deficiency Orthostatic Intolerance

Standing or upright tiltPROCEDURE

stand upright or tilt table test

MicroneurographyPROCEDURE

Recording from sympathetic nerve

QSweatPROCEDURE

quantitative sweat testing

neck cuff stimulationDEVICE

Blood pressure receptors in the neck arteries may be stimulated by applying suction through a collar around the neck.

phenylephrine,isoproterenol,nitroprusside,propranolol,edrophonium,atropine,tyramineDRUG

IV Pharmacological Testing phenylephrine 12.5 - 400 ug, isoproterenol 0.1 - 0.4 ug or higher until desired effect, nitroprusside 0.1 - 1.6 ug/kg, propranolol 1.1 mg/min, edrophonium maximum of 10 mg, atropine .01 mg/kg, tyramine 250-4000 ug or higher until desired effect

clonidine,yohimbine,metoclopramide,alpha-methyldopaDRUG

Oral Pharmacological Testing clonidine 0.1-0.3 mg, yohimbine 5-10 mg, metoclopramide 10 mg, alpha-methyldopa 62.5 mg, placebo

BodPodPROCEDURE

Determination of body composition

Eye examPROCEDURE

Examination of pressure in the eye and eyelid fatiguability. The following eyedrops might be used: 1. 0.5% proparacaine (Alcaine, Allergan, Inc) 2. Fluress (0.4% benoxinate hydrochloride, fluorescein sodium, Akorn, Inc) 3. 0.5%, 1% tropicamide (Mydriacyl, Alcon) 4. Over-the-counter preservative-free artificial tears 5. 0.25%, 2.5% and 10% phenylephrine (Bausch and Lomb) 6. 1% cyclopentolate hydrochloride (Alcon)

Sleep studyPROCEDURE

Recording of sleep pattern overnight

Pain response testingPROCEDURE

Subjects will rate the quality and intensity of 2 pain tasks.

Metabolic chamberPROCEDURE

Determination of metabolic rate via 24hr stay in whole-room indirect calorimeter

Brain function studiesPROCEDURE

Questionnaires and computer tasks, an EEG and an MRI may be used to assess brain function.

Bicycle Exercise TestPROCEDURE

Blood pressure and heart rate may be monitored while exercising on a stationary bicycle.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * severe orthostatic hypotension and other autonomic symptoms but do not meet criteria for standard diagnosis * non-smokers * drug-free * able to give informed consent * free of pulmonary, renal, hematopoietic, hepatic and cardiac disease Exclusion Criteria: * medications affecting the autonomic nervous system * any chronic illness * anemia (Hct\<30) * women of childbearing age who are pregnant or nursing * smokers

Outcomes

Primary Outcomes

hemodynamic changes with standing

Time frame: following test

Secondary Outcomes

blood and urine hormones

Time frame: after test

blood volume

Time frame: during supine and/or upright postures

sympathetic nerve activity

Time frame: during stimulation of sympathetic nervous system

quantitative sweat testing

Time frame: 2 hours

Eye function

Time frame: once

Sleep efficiency

Time frame: once

Metabolic rate

Time frame: once

Pain response

Time frame: once

Responses on questionnaires and computer tasks designed to assess brain function

Time frame: once

The Pathophysiology of Orthostatic Hypotension

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes