Diaphragm Function and Diver Endurance

This project will test the following hypotheses:

1. Training of the inspiratory muscles increases underwater endurance and reduces hypercapnia in divers.
2. 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.
3. Inspiratory muscle training increases hypercapnia ventilatory response (gain) in those individuals with a low gain.
4. Variability in oxygen (O2) and carbon dioxide (CO2) permeability of erythrocyte membranes is a determining factor in underwater exercise performance.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Muscles
• Intervention / Treatment: Other: Carbon monoxide 200 ppm in air

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Natoli, MS; Phone Number: 9196846726; Email: michael.natoli@duke.edu
• Study Contact Backup: Name: Richard E Moon, MD; Phone Number: 9196848762; Email: richard.moon@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Richard E Moon, MD; Phone Number: 919-684-8762; Email: richard.moon@duke.edu
      • Contact: Michael Natoli, MS; Phone Number: 919-684-6726; Email: michael.natoli@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Respiratory Muscle Training Breathing Low Dose Carbon Monoxide; 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; Low dose carbon monoxide
Sham Comparator: Respiratory Muscle Training Breathing Air; 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; Low dose carbon monoxide

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Case Western Reserve University
• Investigators: Principal Investigator: Richard E Moon, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: December 17, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Diaphragm function; Control of breathing; Gas channels; Blood gases
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gasotransmitters; Carbon Monoxide
• Other Study ID Numbers: Pro00107090

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No