Histamine as a Molecular Transducer of Adaptation to Exercise

Study Overview
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Brief Summary
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This study is investigating the role of histamine in generating adaptation to exercise

Detailed Description
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Exercise promotes and maintains healthy cardiovascular, musculoskeletal, and metabolic function, but the signals and mechanisms which transduce these effects are poorly understood. Histamine plays a role in some of the positive benefits of exercise. The goal of this study is to determine the factors that regulate exercise's effects on endothelial and vascular function, with a focus on histamine released from mast cells in skeletal muscle. Participants will perform exercise or participate in interventions like heating that may replicate some of the effects of exercise. During most experiments, investigators will insert an intravenous catheter in an arm vein and microdialysis probes in the leg, collect dialysate from the microdialysis probe and blood from the vein, record noninvasive measures, and have the participants perform exercise or undergo heating.

Official Title
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Histamine as a Molecular Transducer of Adaptation to Exercise

Conditions
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Postexercise Hypotension

Intervention / Treatment
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* Behavioral: Aerobic Exercise
* Drug: alpha-FMH
* Behavioral: Resistance and Aerobic Exercise
* Drug: Antihistamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 -40 Exclusion Criteria: Systolic ≥ 120 Diastolic ≥ 80 Body mass index (BMI) ˃ 28 kg/m2 Prior diagnosis of cardiovascular disease, diabetes, autonomic disorders, or asthma Smoking or nicotine use Ongoing medical therapy (other than birth control) Ongoing use of over-the-counter or prescription antihistamines Allergies or hypersensitivities to drugs, local anesthetics, skin disinfectants, adhesives, or latex Pregnant, breastfeeding subjects, or planning to become pregnant in the next 12 months Mobility restrictions that interfere with physical activity High physical activity based on International Physical Activity Questionaire (IPAQ1) Non-English speaking

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a series of Basic Experimental Studies with Humans (BESH, as defined by PA-20-184). Subjects are enrolled (non-randomized) in different arms of the overall study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic Exercise<br>Blood and skeletal muscle microdialysate collected during dynamic knee-extension exercise | Behavioral: Aerobic Exercise<br>* Subjects will complete a single bout of aerobic exercise.<br>|
| Experimental: Heating<br>Blood and skeletal muscle microdialysate collected during local and/or whole body heating | Drug: alpha-FMH<br>* Subjects will undergo either local heating with diathermy or whole body heating with far-infrared sauna.<br>* Other names: Heating;|
| Experimental: Resistance and Aerobic Exercise<br>Blood and urine collected during recovery from two modalities of exercise | Behavioral: Resistance and Aerobic Exercise<br>* Subjects will complete bouts of resistance and aerobic exercise.<br>|
| Experimental: Aerobic Exercise and Muscle Perfusion<br>Muscle perfusion measured during aerobic exercise | Behavioral: Aerobic Exercise<br>* Subjects will complete a single bout of aerobic exercise.<br>Drug: Antihistamine<br>* Subjects will complete a single bout of aerobic exercise under placebo vs antihistamine conditions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of mast cell degranulation | Beta-hexosaminidase release from mast cells in mast cell degranulation bioassay when exposed to intramuscular dialysate from exercising individuals | One hour | 
| Histamine concentration | Histamine concentration in intramuscular dialysate | One hour | 
| Histamine metabolites | Concentration of histamine metabolites in blood and urine | 24 hours | 
| Muscle perfusion | Skeletal muscle tissue oxygen index | One hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Histamine, Mast cell, Exercise