Autonomic Control of the Circulation and the Venous Distension Reflex
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Microneurography (MSNA)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
These two trials (A and B) will be performed in random order and in a doubleblind fashion for subjects and the data analyzing team. The medical staff who prepare and administrate the drugs and monitor the subject's safety, will not be blinded.
入排标准
- 年龄范围
- 21 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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/
排除标准
- •Are free of acute or chronic medical conditions
- •Are 21 - 35 years of age (inclusive)
- •Weigh over 50 kg
- •Exclusion Criteria
- •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
研究组 & 干预措施
Ketorolac
The Wrist-to-Elbow occlusion procedure will be performed followed by 2 ketorolac tromethamine + saline infusions into the occluded arm.
干预措施: ketorolac tromethamine (Drug)
Control
The Wrist-to-Elbow occlusion procedure will be performed followed by 2 saline only infusions into the occluded arm.
干预措施: Wrist-to-elbow (W-E) occlusion (Other)
Control
The Wrist-to-Elbow occlusion procedure will be performed followed by 2 saline only infusions into the occluded arm.
干预措施: saline control (Drug)
Ketorolac
The Wrist-to-Elbow occlusion procedure will be performed followed by 2 ketorolac tromethamine + saline infusions into the occluded arm.
干预措施: Wrist-to-elbow (W-E) occlusion (Other)
结局指标
主要结局
Microneurography (MSNA)
时间窗: Recorded continuously during the 3-4 hour study visit
This technique provides direct recordings of sympathetic nerve activity directed to blood vessels in skeletal muscle and will be our primary index of sympathoexcitation. This procedure may be performed in the either leg. External mapping of the peroneal or tibial nerve course (10-60 volts, 1-5msec, 1Hz) will be performed just behind the fibular head of the leg or in the popliteal fossa. A reference electrode will be placed subcutaneously about 2-3 cm away from the recording site. Multiunit recordings of MSNA in the leg will be obtained by transcutaneous placement of a tungsten microelectrode (insulated 200 ?m diameter with a tapered un-insulated 1-5 ?m tip) into C-fiber containing fascicle in the nerve. The electrode will be manipulated to yield a neurogram with characteristic bursts of MSNA, that will be amplified, filtered, rectified and integrated to obtain a mean voltage neurogram. Analysis consists of counting burst frequency and amplitude.
Vein size with MRI
时间窗: Recorded continuously during the 3-4 hour study visit
Forearm cross sectional images will be obtained in HMC MRI facility. The proton weighted images will be obtained with Siemens Magnetom Trio 3T scanner (Siemens Medical Solutions, Erlangen, Germany). Contrast agents are not required for this completely noninvasive technique. The subject will lie supine inside the MRI scanner, and will be instrumented with an 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.
次要结局
- Laser-Doppler flowmetry(Recorded continuously during the 3-4 hour study visit)
- Strain gauge(Recorded continuously during the 3-4 hour study visit)
- Impedance(Recorded continuously during the 3-4 hour study visit)
- Heart Rate(Recorded continuously during the 3-4 hour study visit)
- Blood Pressure(Recorded continuously during the 3-4 hour study visit)
研究者
Jian Cui
Professor of Medicine
Milton S. Hershey Medical Center