RecruitingEarly Phase 1NCT03513770

Autonomic Control of the Circulation and VDR

Autonomic Control of the Circulation and the Venous Distension Reflex

Sponsor

Milton S. Hershey Medical Center

Enrollment

18 participants

Start Date

Aug 14, 2019

Study Type

INTERVENTIONAL

Conditions

Blood Pressure Venous Distension Reflex

Summary

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

Min Age: 21 YearsMax Age: 35 Years

Inclusion Criteria3

Are capable of giving informed consent
Are any race or ethnicity
Are fluent in written and spoken English

Exclusion Criteria16

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
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

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Interventions

OTHERWrist-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 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.

DRUGketorolac 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 induce venous distension.

DRUGsaline 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.