Characterizing Hypoxic Apnea Intra-individual Repeatability (CHAIR)

Characterizing the Repeatability and Reproducibility of Cardiovascular Responses to Hypoxic Apneas

Apneas (breath-holds) are increasingly being tested in human subjects to understand how the human body operates. Apneas decrease heart rate and increase blood pressure. These findings are driving current research into the effects of oxygen concentrations on the heart rate and blood pressure responses to apneas and the effect of breath-hold training on these responses. The interest in apnea research is three-fold:

1. Apneas are a nervous system stressor that can help researchers better understand the fundamental operation of the human body;
2. Elite divers can use findings from research to better their training and performance; and
3. The scientific understanding of apneas may translate to a better understanding of sleep apnea.

Despite this interest, little is known about the repeatability (the consistency within a single day) and reproducibility (the consistency between days) in the heart rate and blood pressure responses to apneas. This uncertainty limits the scientific interpretations from previous results. This study aims to determine the repeatability and reproducibility of heart rate and blood pressure responses to apneas. The goals of the study are:

1. To provide greater certainty to previous results; and
2. Inform best practices for future studies.

The study requires 20 healthy volunteers (10 females) and will measure heart rate, blood pressure, breathing parameters (expired gas concentrations, breathing volume and rate), and oxygen saturation. During the protocol, participants will complete two maximal voluntary apneas and five test apneas. The test apneas will all be the same length based on the longer of the two maximal voluntary apneas. Before each apnea, participants will also breathe low oxygen concentrations (hypoxia). Hypoxia provides a bigger decrease in heart rate during apneas than room air which makes it easier to see changes in heart rate responses between apneas (i.e., bigger signal-to-noise ratio). Participants will complete two identical test sessions on back-to-back days. The differences in heart rate and blood pressure responses to the five apneas within each session will determine repeatability and the differences between sessions will determine reproducibility. The investigators hypothesize that repeatability will be good and that repeatability within a session will be better than reproducibility between sessions.

Study Overview

• Status: Completed
• Conditions: Apnea; Hypoxia
• Intervention / Treatment: Other: Apnea Following Isocapnic Hypoxia

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2E1
      • University of Alberta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males and females between the ages of 18-70

Exclusion Criteria:

• Having known cardiovascular or nervous system disease
• Low or high blood pressure (< 90/60 or >139/85, respectively)
• Taking any prescribed medications (other than oral contraceptives) that may affect cardiovascular system function
• Females who may be pregnant (self-reported)
• Involved in other studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apnea Following Isocapnic Hypoxia	Other: Apnea Following Isocapnic Hypoxia; Decreasing end-tidal partial pressure of oxygen to 50 mmHg for five minutes, targeting 80-85% peripheral oxygen saturation. The end-tidal partial pressure of carbon dioxide will remain +1 mmHg above baseline levels. After five minutes of hypoxia, participants will complete an apnea.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate	Electrocardiogram (lead II)	Continuous collection during both visits (2 hours on back-to-back days). Data will be extracted during free breathing (1 minute average before each apnea) and during apneas (beat-by-beat extraction from the 10 beats preceding resumption of breathing).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure	Finger Photoplethysmography	Continuous collection during both visits (2 hours on back-to-back days). Data will be extracted during free breathing (1 minute average before each apnea) and during apneas (beat-by-beat extraction from the 10 beats preceding resumption of breathing).
Cardiac Arrhythmias	Assessed using electrocardiogram (lead II) by a trained researcher and reviewed by a cardiologist. Arrhythmias observable in lead II will be reported as a binary (i.e., yes/no) for each individual for each apnea. Example arrhythmias are premature atrial contractions and sinus pauses, though many more exist.	Continuous collection during both visits (2 hours on back-to-back days). Data will be extracted during apneas (beat-by-beat observation from the 10 beats preceding the resumption of breathing).
Peripheral Oxygen Saturation	Pulse Oximetry	Continuous collection during both visits (2 hours on back-to-back days). Data will be extracted during free breathing (1 minute average before each apnea) and during apneas (10 beats preceding the resumption of breathing to 1 minute after apnea end).
Rating of Perceived Exertion	Participants Rate the Effort of their Apnea using the Modified Borg Scale with scores from 1 to 10 with 1 representing no effort and 10 representing a maximal effort.	Apnea (immediately following apnea)
Apnea Duration	Time, in seconds, from the end of the last breath preceding the apnea to the resumption of breathing.	Start to end of apnea: apnea start determined using cessation of flow through the pneumotachometer, apnea end determined using respiratory belt strain gauge. Estimated apnea durations are 15-30 seconds.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
End-Tidal Oxygen	S-3A/I Oxygen Analyzer & Model N-22M Sensor, AEI Technologies	Continuous collection during both visits (2 hours on back-to-back days). Data will be extracted during free breathing (1 minute average before apnea).
End-Tidal Carbon Dioxide	CD-3A Carbon Dioxide Analyzer & P-61B Sensor	Continuous collection during both visits (2 hours on back-to-back days). Data will be extracted during free breathing (1 minute average before apnea).
Minute Ventilation	Pneumotachometer	Continuous collection during both visits (2 hours on back-to-back days). Data will be extracted during free breathing (1 minute average before apnea).

Collaborators and Investigators

• Sponsor: University of Alberta

Publications and helpful links

General Publications

• Weir JP. Quantifying test-retest reliability using the intraclass correlation coefficient and the SEM. J Strength Cond Res. 2005 Feb;19(1):231-40. doi: 10.1519/15184.1.
• Hopkins WG. Measures of reliability in sports medicine and science. Sports Med. 2000 Jul;30(1):1-15. doi: 10.2165/00007256-200030010-00001.
• Stanforth PR, Gagnon J, Rice T, Bouchard C, Leon AS, Rao DC, Skinner JS, Wilmore JH. Reproducibility of resting blood pressure and heart rate measurements. The HERITAGE Family Study. Ann Epidemiol. 2000 Jul;10(5):271-7. doi: 10.1016/s1047-2797(00)00047-8.
• Busch SA, Davies H, van Diepen S, Simpson LL, Sobierajski F, Riske L, Stembridge M, Ainslie PN, Willie CK, Hoiland R, Moore JP, Steinback CD. Chemoreflex mediated arrhythmia during apnea at 5,050 m in low- but not high-altitude natives. J Appl Physiol (1985). 2018 Apr 1;124(4):930-937. doi: 10.1152/japplphysiol.00774.2017. Epub 2017 Dec 21.
• Busch SA, van Diepen S, Steele AR, Meah VL, Simpson LL, Figueroa-Mujica RJ, Vizcardo-Galindo G, Villafuerte FC, Tymko MM, Ainslie PN, Moore JP, Stembridge M, Steinback CD. Global REACH: Assessment of Brady-Arrhythmias in Andeans and Lowlanders During Apnea at 4330 m. Front Physiol. 2020 Jan 22;10:1603. doi: 10.3389/fphys.2019.01603. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2024
• Primary Completion (Actual): June 28, 2024
• Study Completion (Actual): June 28, 2024

Study Registration Dates

• First Submitted: April 21, 2024
• First Submitted That Met QC Criteria: May 3, 2024
• First Posted (Actual): May 6, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 1, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Heart Rate; Reproducibility; Repeatability
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Apnea; Hypoxia
• Other Study ID Numbers: Pro00138947

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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