Diaphragm Function and Diver Endurance

Study Overview
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Brief Summary
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This project will test the following hypotheses: Training of the inspiratory muscles increases underwater endurance and reduces hypercapnia in divers. Inspiratory muscle training while breathing low concentration carbon monoxide (200 ppm) for 30 minutes daily improves diaphragm performance to a greater degree than the same training breathing air. Inspiratory muscle training increases hypercapnia ventilatory response (gain) in those individuals with a low gain. Variability in oxygen (O2) and carbon dioxide (CO2) permeability of erythrocyte membranes is a determining factor in underwater exercise performance.

Detailed Description
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The aims of this project are to: (1) test a method that could increase personal endurance and reduce excessive rise in blood carbon dioxide during underwater exercise in divers; and (2) understand the mechanisms by which red blood cells transport oxygen and carbon dioxide and their possible effects on exercise capacity. During underwater exercise, personal endurance capacity and elevated blood PCO2 are key parameters that affect a diver's safety and performance. Unlike exercise on dry land, hypercapnia often occurs during dives and can impair cognitive function and predispose the diver to central nervous system (CNS) oxygen toxicity and convulsions underwater. Some people intrinsically have low ventilatory chemosensitivity, and are more likely to develop hypercapnia during a dive. Lack of stamina may also be a mission-critical variable, and both endurance and the ability to control blood carbon dioxide depend on the respiratory muscle (mainly diaphragm) function, for which endurance capacity is related to mitochondrial number. Previous studies from our lab have demonstrated increased mitochondrial biogenesis with training while breathing a low, sub-toxic (200 ppm) level of carbon monoxide. In this study we will test the effect of daily respiratory muscle training with and without added carbon monoxide on respiratory muscle power, diaphragm thickness, respiratory muscle endurance and exercise endurance during a subsequent dive to 50 feet of sea water. Arterial PCO2 and lactic acid levels will be measured during exercise tests before and after training. Transport of O2 and CO2 through erythrocyte cell membranes occurs mostly through channels. Erythrocytes from volunteers in this study will be tested for O2 and CO2 permeability, and to correlate gas transport efficiency with exercise performance and blood PCO2.

Official Title
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Diaphragm Function and Diver Endurance

Conditions
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Respiratory Muscles

Intervention / Treatment
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* Other: Carbon monoxide 200 ppm in air


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal volunteers Non-smokers Range of hypercapnic ventilatory responses VO2peak ≥35 mL.kg-1.min-1 (males) ≥30 mL.kg-1.min-1 (females) Exclusion Criteria: Pregnancy Cardiorespiratory disease, including hypertension Neuromuscular disease Anemia Hemoglobinopathy, including sickle cell disease and trait

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Mixed model with repeated measures
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Respiratory Muscle Training Breathing Low Dose Carbon Monoxide<br>Carbon monoxide 200 ppm in air breathing during daily 30 minute inspiratory loading training sessions. Subjects will breathe the experimental gas through a mouthpiece with nose-clip in place. | Other: Carbon monoxide 200 ppm in air<br>* Low dose carbon monoxide<br>|
| Sham Comparator: Respiratory Muscle Training Breathing Air<br>Air breathing during daily 30 minute inspiratory loading training sessions. Subjects will breathe air through a mouthpiece with nose-clip in place. | Other: Carbon monoxide 200 ppm in air<br>* Low dose carbon monoxide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Underwater endurance change | Endurance during continuous underwater exercise at a depth of 50 ft below the surface | Baseline, 6 weeks | 
| Arterial PCO2 change | Blood gases during and at end of exercise | Baseline, 6 weeks | 
| Ventilatory chemosensitivity change | Hypercapnic ventilatory response (VE.min-1.mmHg) | Baseline, 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erythrocyte gas channel analysis | Stopped-flow analysis of O2 offloading from Hb of (a) intact RBCs, (b) Hb in hemolysate | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Control of breathing, Diaphragm function, Gas channels, Blood gases