Dietary Sodium's Effect on Urinary Sodium and Dopamine Excretion in Patients With Postural Tachycardia Syndrome

Dietary Sodium's Effect on Urinary Sodium and Dopamine Excretion in Patients With Postural Tachycardia Syndrome

Dietary Sodium's Effect on Urinary Sodium and Dopamine Excretion in Patients With Postural Tachycardia Syndrome

Patients with Postural Tachycardia Syndrome (POTS) may not adequately expand their plasma volume in response to a high sodium diet. Mechanisms involved in the regulation of plasma volume, such as the renin-angiotensin-aldosterone system and renal dopamine (DA), may be impaired in POTS and may respond inappropriately to changes in dietary sodium. The investigators propose that the changes in urinary sodium and dopamine excretion caused by consuming low-sodium and high-sodium diets will be different between patients with POTS and healthy volunteers. The purpose of this study is to determine (1) whether changes in dietary sodium level appropriately influence sodium excretion in POTS; (2) whether changes in dietary sodium level appropriately influence DA excretion in POTS; (3) whether a high dietary sodium level appropriately expands plasma volume in POTS; and (4) whether patients with POTS have improvements in their orthostatic tachycardia and symptoms as a result of a high dietary sodium level.

Study Day 1 Start 150 mEq Na+/day diet (POTS patients as inpatients; healthy control subjects with Clinical Research Center(CRC)- provided outpatient diet); consume 1.5-2 liters of water per day Start a 24hour (24hr) urine collection (for sodium (Na+), potassium (K+), creatinine (Cr), fractionated catecholamines) Blood work Study Days 2-5 Continue 24hr urine collection Start STUDY DIET (10 mEq Na+/day or 300 mEq Na+/day in a random order) after 3 meals of 150 mEq Na+/day are complete; consume 1.5-2 liters of water per day On Day 5, a 24 hr Holter combined ECG monitor and BP monitor will be placed on the subjects. Study Day 6 Continue STUDY DIET; consume 1.5-2 liters of water per day Remove 24hr Holter combined ECG monitor and BP monitor from subject Continue 24hr urine collection (for Na+, K+, Cr, fractionated catecholamines) Admit to CRC in afternoon (healthy control subjects only, as POTS patients will have already been admitted). Each subject will spend the night in the CRC and remain supine Nothing by mouth (NPO) after midnight for study next day Study Day 7 Awaken early (~6am) to void (still collecting 24hr urine) Patient returns to bed, IV catheter inserted Posture Study (in morning; between 7-8am ideally) Blood pressure and heart rate will be measured while supine and then while standing for up to 30 minutes We will draw blood in each body position to measure electrolytes and hormones that regulate blood pressure and blood volume Subjects will rate symptoms during supine period and at end of stand using Vanderbilt Orthostatic Symptoms Score (VOSS) Total Blood Volume (DAXOR)- using injection of iodinated I-131 tagged human serum albumin nominally 25 micro-Ci of radiation blood samples drawn through IV catheter before injection and for ~30 minutes post-injection (total - 25 ml) This will be done after supine assessment, but before standing the subject up Exercise Capacity Test (in the afternoon) Will estimate maximal oxygen consumption (VO2 max). This test will be conducted on a stationary bicycle. Effort will be gradually increased while expired air is measured during exhaustive physical work. All procedures are repeated at least a month later with the 2nd level of dietary salt. (Randomized to high or low salt in the first phase, the second phase is the remaining level)

Randomization tables will be used to determine whether the 10 milliequivalents (mEq) sodium/day or 300 mEq sodium/day diet will be consumed first. Both diets will be completed on each subject (randomized crossover study), so all of the study procedures (after screening) will be repeated.

POTS and healthy controls will be randomly assigned the order of dietary sodium levels. All procedures are performed at both levels. The high sodium diet will provide 300 milliequivalents (mEq) sodium/day.

POTS and healthy controls will be randomly assigned the order of dietary sodium levels. All procedures are performed at both levels. The low sodium diet will provide 10 mEq sodium/day.

Using injection of iodinated I-131 tagged human serum albumin nominally 25 micro-Ci of radiation, blood samples are drawn before and 30 minutes after injection.

subjects breathe room air through a mouthpiece and exhale the air into a tube that connects to a machine (metabolic cart) that analyzes carbon dioxide and oxygen content, which allows the investigator to calculate the amount of oxygen they are using under resting and exercise conditions.

Blood pressure and heart rate will be measured while supine and then while standing for up to 30 minutes. Blood will be drawn in each position to measure hormones that regulate blood pressure and blood volume.

Plasma volume (PV) was determined by the indicator tracer-dilution technique, using the DAXOR Blood Volume Analyzer (BVA)-100 system (DAXOR Corporation), on Day 7 of the low sodium and high sodium dietary interventions.

Whether the magnitude of the heart rate increase that occurs in patients with POTS when moving from a supine to an upright position is attenuated by a High Sodium diet relative to a Low Sodium diet. Heart rate was assessed after overnight rest and fasting after midnight, following at least 60 minutes of lying quietly. Heart rate was then measured at intervals after subjects had been standing for up to 30 minutes (as tolerated). Differences between supine and standing values are presented for 5 minutes standing (or maximal stand if <5 minutes) since several patients were unable to stand for 10 minutes. Data in POTS patients were compared to that of Healthy Controls.

Whether upright symptoms were improved in patients with POTS on a High Sodium diet relative to a Low Sodium diet. Patients were asked to report their standing symptom burden at the end of the Stand portion of the posture study, using the Vanderbilt Orthostatic Symptoms Scale (VOSS). They rated the severity of nine symptoms (palpitations, lightheadedness, mental confusion, blurred vision, shortness of breath, tremulousness, chest discomfort, headache, and nausea) on a scale ranging from a minimum of 0 (reflecting an absence of symptoms) to a maximum score of 10. The sum of the individual symptom scores was used to calculate orthostatic symptom burden for each participant. The lowest possible total score was 0, if a participant scored all 9 questions as 0, and the highest possible score was 90, if a participant scored all 9 questions as 10. Higher scores indicated worse symptoms.

Urinary sodium excretion will be measured every 24 hours as the participant adapts from the 150 mEq Na/day diet to the 10 and 300 mEq Na/day diets.

Urinary dopamine excretion will be measured every 24 hours as the participant adapts from the 150 mEq Na/day diet to the 10 and 300 mEq Na/day diets.

Urinary sodium excretion will be measured every 24 hours as the participant adapts from the 150 mEq Na/day diet to the 10 and 300 mEq Na/day diets.

Urinary sodium excretion will be measured every 24 hours as the participant adapts from the 150 mEq Na/day diet to the 10 and 300 mEq Na/day diets.

Urinary sodium excretion will be measured every 24 hours as the participant adapts from the 150 mEq Na/day diet to the 10 and 300 mEq Na/day diets

Urinary sodium excretion will be measured every 24 hours as the participant adapts from the 150 mEq Na/day diet to the 10 and 300 mEq Na/day diets.

Urinary dopamine excretion will be measured every 24 hours as the participant adapts from the 150 mEq Na/day diet to the 10 and 300 mEq Na/day diets.

Urinary dopamine excretion will be measured every 24 hours as the participant adapts from the 150 mEq Na/day diet to the 10 and 300 mEq Na/day diets.

Urinary dopamine excretion will be measured every 24 hours as the participant adapts from the 150 mEq Na/day diet to the 10 and 300 mEq Na/day diets.

Urinary dopamine excretion will be measured every 24 hours as the participant adapts from the 150 mEq Na/day diet to the 10 and 300 mEq Na/day diets.

Inclusion Criteria: Premenopausal patients with POTS and healthy volunteers, 18-50 years old, who are non-smokers and free of medications with the potential to influence blood pressure Patients diagnosed with postural tachycardia syndrome by the Vanderbilt Autonomic Dysfunction Center Patients who Increase heart rate ≥30 beats/min with position change from supine to standing (10 minutes) For patients, chronic symptoms consistent with POTS that are worse when upright and get better with recumbence Only female participants are eligible. Since 80-90% of POTS patients are female, and there can be differences in measures with the menstrual cycle, including a small number of males might introduce a significant amount of noise. Able and willing to provide informed consent Exclusion Criteria: Smokers Overt cause for postural tachycardia, i.e., acute dehydration Significant cardiovascular, pulmonary, hepatic, or hematological disease by history or screening results Positive pregnancy test or breastfeeding Hypertension defined as BP>145/95 off medications when supine or needing antihypertensive medication Other factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies or an unpredictable schedule Unable to give informed consent