Splanchnic Venous Capacitance in Postural Tachycardia Syndrome
Mechanism of Glucose-dependent Insulinotropic Polypeptide (GIP) on Splanchnic Venous Capacitance in Postural Tachycardia Syndrome
Vanderbilt University Medical Center
50 participants
Feb 25, 2023
INTERVENTIONAL
Conditions
Summary
Postural tachycardia syndrome (POTS) affects ≈3 million young people, characterized by chronic presyncopal symptoms characterized by dizziness, lightheadedness, and orthostatic tachycardia that occur while standing. Across-sectional survey found that 25% of these patients complains that meals rich in carbohydrates are among the factors that further exacerbate POTS's symptoms and cause a myriad of gastrointestinal symptoms. The splanchnic circulation is the largest blood volume reservoir of the human body, storing ≈25% of the total blood volume and contributing to sudden, and large, fluctuations in the stroke volume (SV). The orthostatic changes in systemic hemodynamics are particularly magnified after meals, due to increased blood volume sequestration triggered by the release of gastrointestinal peptides with vasodilatory properties. The purpose of this study is to determine if the worsening orthostatic tachycardia and symptoms after glucose ingestion in POTS patients are due to a greater increase in splanchnic venous capacitance and excessive blood pooling on standing as compare to Healthy controls. The study will also determine if glucose-induced GIP secretion increases splanchnic venous capacitance, orthostatic tachycardia and worsening POTS postprandial symptoms. For this purpose subjects will be further randomized to either saline versus GIP(3-30)NH2 acute infusion, to measure the changes their splanchnic venous capacitance and superior mesenteric arterial flow before and after a 75-g oral glucose challenge during supine and 45-degree head-up tilt positions (orthostatic challenge) for up to 3 hours.
Eligibility
Inclusion Criteria6
- Between 18 and 50years of age
- Cases: Diagnosis of POTS with presyncope symptoms after meals Or
- Controls:
- With no significant past medical history, non-smokers and not on chronic medications.
- Body mass index (BMI) between 18.5 to 29.9 kg/m2
- If pre-menopausal women: must have regular menstrual cycle.
Exclusion Criteria23
- BMI above ≥30 kg/m2
- Irregular menstrual cycle
- Intolerance to CPAP.
- Chronic use of acetaminophen
- Heart problems: myocardial infarction, angina, heart failure, stroke
- Undergone any heart related procedures or stents or on pacemaker.
- Uncontrolled hypertension.
- Type 1 or type 2 diabetes mellitus
- Pregnant or breast-feeding women.
- Impaired liver function
- Impaired Kidney function test.
- Anemia (Hematocrit\<34%).
- Ongoing substance abuse.
- Subjects with abnormal EKG
- History of seizures.
- Diagnosed with neuropathy due to any reason
- History of neck surgery.
- Smoker,
- On statin therapy for high cholesterol
- Rheumatoid arthritis.
- On oral corticosteroids,
- Current infections
- Documented of moderate decrease in blood volume
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Interventions
While segmental bioimpedance is monitored, continuous positive airway pressure (CPAP) will be applied sequentially at 0, 4, 8, 12, and 16 cm H2O for about 30 seconds each. This positive airway pressure will increase the intrathoracic pressure, which is transmitted to the venous circulation. Pressure (CPAP pressure, X axis) - volume (splanchnic vascular volume measured by segmental impedance and expressed as % change from baseline, Y axis) relationships are then constructed to assess for splanchnic venous capacitance
While segmental bioimpedance is monitored, continuous positive airway pressure (CPAP) will be applied sequentially at 0, 4, 8, 12, and 16 cm H2O for about 30 seconds each. This positive airway pressure will increase the intrathoracic pressure, which is transmitted to the venous circulation. Pressure (CPAP pressure, X axis) - volume (splanchnic vascular volume measured by segmental impedance and expressed as % change from baseline, Y axis) relationships are then constructed to assess for splanchnic venous capacitance
Participants with POTS will be randomize to either saline versus GIP(3-30)NH2 acute infusion. We will measure changes in their splanchnic venous capacitance and superior mesenteric arterial flow before and after a 75-g oral glucose challenge during supine and 45-degree head-up tilt positions (orthostatic challenge) for up to 3 hr. Notably, we will assess changes in venous capacitance using segmental impedance to measure the effect of graded positive airway pressure (CPAP) on splanchnic blood volume.
Participants with POTS will be randomize to either saline versus GIP(3-30)NH2 acute infusion. We will measure changes in their splanchnic venous capacitance and superior mesenteric arterial flow before and after a 75-g oral glucose challenge during supine and 45-degree head-up tilt positions (orthostatic challenge) for up to 3 hr. Notably, we will assess changes in venous capacitance using segmental impedance to measure the effect of graded positive airway pressure (CPAP) on splanchnic blood volume.
Locations(1)
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NCT05375968