Autonomic Control of the Circulation and VDR

ConditionsVenous Distension Reflex Blood Pressure

Trial statusRecruiting

Trial phaseEarly Phase 1

Trial typeInterventional

Biological sexAll

Age21-35

SponsorMilton S. Hershey Medical Center

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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/

Disqualifiers

Are free of acute or chronic medical conditions

Are 21 - 35 years of age (inclusive)

Weigh over 50 kg

Are less than 21 or over 35 years of age

Trial design

Design model

Crossover

Treatments tested in this trial

Wrist-to-elbow (W-E) occlusion
Other intervention
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 fully inflated, the next cuff in the sequence will be inflated. Cuffs are inflated in sequence until the elbow cuff is inflated. After a 10-15 second period to allow blood to drain, the upper arm cuff will inflate (up to 250 mmHg) to keep any additional blood from entering the forearm. Next, the cuffs on the forearm will be removed but the upper arm cuff will remain inflated.
ketorolac tromethamine
Drug
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 induce venous distension.
saline control
Drug
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.

Treatment groups

18 Participants

are divided into 2 treatment groups

Group A: KetorolacExperimental treatment 2 interventions

Group B: ControlPlacebo comparator 2 interventions

Trial outcomes

Primary outcomes

Microneurography (MSNA)

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.

Time frame