Autonomic Control of the Circulation and VDR

Официальное название

Autonomic Control of the Circulation and the Venous Distension Reflex

Обзор

The study objective of this project is to examine the mechanisms of the venous distension reflex (VDR) in humans. We hypothesize that COX blockade with ketorolac tromethamine, an intravenous NSAID, will attenuate the muscle sympathetic nerve activity (MSNA) response to limb venous distension. To gain further insight into whether the COX byproducts directly stimulate chemically-sensitive afferents, or enable venodilation and indirectly evoke afferent stimulation, we will measure vein size using 3T MRI during venous distention with and without ketorolac infusions.

Подробное описание

We will use a prospective observational design to examine if a COX blockade will inhibit the MSNA response to venous distension (Aim1), and if a COX blockade will alter vein sizes during venous distension (Aim2). Each subject will serve as their own control.

Aim 1:

An IV will be inserted in the antecubital fossa of one arm, and the wrist-to-elbow occlusion will be performed.

To block the COX system, 6 mg ketorolac tromethamine in 10 ml saline will be infused into the forearm over 1 minute (Infusion 1). After 10 minutes, a second infusion of ketorolac tromethamine (up to 3 mg) in 5% of the forearm volume of saline,( \~40-60 ml) will be infused into the occluded forearm at a rate of \~ 30 ml/min (Infusion 2). Five minutes of data will then be collected before releasing the upper arm cuff. Infusion 1 is to block the COX pathway, while infusion 2 is to induce venous distension.

In the saline control trial, saline (without ketorolac) in identical volumes as those in the COX blockade trial will be performed on a separate day.

Aim 2:

The subject will lie supine inside the MRI scanner. The subject will be instrumented with cuffs for the wrist-to-elbow occlusion procedure on one arm, and cuffs for automated BP and HR measurements from the other arm, The images will be obtained before and during the wrist-to-elbow occlusion procedure. The sizes of veins (i.e. cross sectional area) will be measured offline.

Вмешательства

• Другое Wrist-to-elbow (W-E) occlusion
  An IV will be inserted in the antecubital fossa of one arm. The arm will be fitted with occlusion cuffs arranged in a continuous fashion from the wrist to the elbow. A final cuff will be placed on the upper arm. The cuffs from the wrist to the elbow will be inflated to the same pressure of up to 300 mmHg using a pressurized air tank. First, the subject?s arm will be elevated and the subject will make a fist to squeeze blood from the hand. Then the wrist cuff will be inflated. Once that cuff is
• Препарат ketorolac tromethamine
  In the COX blockade trial, just after the Wrist-to-elbow occlusion, 6 mg ketorolac tromethamine in 10 ml saline will be infused into the forearm over 1 minute. After 10 minutes, a second infusion of ketorolac tromethamine (up to 3 mg) in 5% of the forearm volume of saline,( \~40-60 ml) will be infused into the occluded forearm at a rate of \~ 30 ml/min. Five minutes of data will then be collected before releasing the upper arm cuff. Infusion 1 is to block the COX pathway, while infusion 2 is to
• Препарат saline control
  In the saline control trial performed on a separate day, saline (without ketorolac) in identical volumes as those in the COX blockade trial, will be infused.

Первичные конечные точки

• Microneurography (MSNA) [Срок оценки: Recorded continuously during the 3-4 hour study visit]
• Vein size with MRI [Срок оценки: Recorded continuously during the 3-4 hour study visit]

Вторичные конечные точки (5)

• Heart Rate [Срок оценки: Recorded continuously during the 3-4 hour study visit]
• Blood Pressure [Срок оценки: Recorded continuously during the 3-4 hour study visit]
• Laser-Doppler flowmetry [Срок оценки: Recorded continuously during the 3-4 hour study visit]
• Strain gauge [Срок оценки: Recorded continuously during the 3-4 hour study visit]
• Impedance [Срок оценки: Recorded continuously during the 3-4 hour study visit]

Критерии участия

Критерии включения

• Are capable of giving informed consent
• Are any race or ethnicity
• Are fluent in written and spoken English
• Have a satisfactory history and physical exam to meet inclusion/exclusion criteria
• Are free of acute or chronic medical conditions
• Are 21 - 35 years of age (inclusive)
• Weigh over 50 kg

Критерии исключения

• Are less than 21 or over 35 years of age
• Are Pregnant or nursing women
• Are prisoners or institutionalized individuals or unable to consent
• Any chronic diseases (hypertension, heart, lung, neuromuscular disease, kidney disease, diabetes or cancer).
• Are taking medications that may affect their cardiovascular or nervous system
• Has taken an NSAID within 48 hours of any visit (visit will need to be rescheduled)
• Has never taken NSAIDs and therefore would not know if they are allergic to it
• Have a supine BP >140/90 mmHg
• Have known allergy to ibuprofen-like drugs (NSAIDS) or aspirin
• Have history of asthma or nasal polyps
• Have history of GI bleeding or ulcers
• Subjects with ferromagnetic metal implants
• Subjects who are claustrophobic

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Тройное слепое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• Penn State Milton S. Hershey Medical Center — Hershey

Идентификаторы

NCT: NCT03513770 · STUDY00006585 · R01HL144781

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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