None listed
Conditions
Brief summary
Exercise training has broad benefits for cardiovascular health. Surprisingly, the mechanisms by which these benefits occur are not well understood. Approximately 40% of the reduction in cardiovascular risk following exercise training cannot be attributed to improvements in traditional risk factors (e.g., changes in blood lipids). The chemoreflex is a specialised reflex mechanism that responds to changes in blood gas concentrations, and heightened chemoreflex sensitivity has been identified in chronic cardiovascular disease conditions such as hypertension, heart failure and coronary heart disease. However, it is currently unclear whether the cardiovascular benefits of exercise training are related to a reduction in chemoreflex sensitivity. It is possible that the chemoreflex is implicated in the cardiovascular response to exercise training and this concept is supported by basic animal research, but data are lacking in human participants. The primary objective of this study is to understand whether a community-based exercise training programme alters peripheral and central chemoreflex sensitivity, and peripheral chemoreflex tonicity, in older adults. Recordings of blood pressure, respiration and cerebral blood flow will be obtained from older adults who are enrolled in the GoldFit YMCA exercise training programme. Cross sectional recordings will be obtained from older adults who are regularly exercising, Peripheral chemoreflex sensitivity will be assessed using an isocapnic hypoxia stimulus. Central chemoreflex sensitivity will be assessed using hypercapnia hyperoxia. Peripheral chemoreflex tonicity will be assessed using intermittent exposure to hyperoxia. Cross-sectional comparisons of regularly exercising older adults and sedentary older adults will be made to test the hypothesis that chemoreflex sensitivity is attenuated by exercise training in older adults performing a community-based exercise training intervention. The knowledge provided by this project will help to relieve the burden of cardiovascular disease and support the clinical basis for the application of exercise training as a novel therapy for targeting chemoreceptor over-activity.
Interventions
This is a non-therapeutic mechanistic physiological study.
All of the following procedures will be conducted by the doctoral candidate with assistance from a trained human physiologist staff member. The laboratory where all assessments will take place is located at the Human Physiology Laboratory, Department of Respiratory Physiology, Level 7 Auckland City Hospital, Auckland DHB or the University of Auckland Clinical Research Centre, Park Avenue, University of Auckland Grafton Campus.
Particip
This is a non-therapeutic mechanistic physiological study. All of the following procedures will be conducted by the doctoral candidate with assistance from a trained human physiologist staff member. The laboratory where all assessments will take place is located at the Human Physiology Laboratory, Department of Respiratory Physiology, Level 7 Auckland City Hospital, Auckland DHB or the University of Auckland Clinical Research Centre, Park Avenue, University of Auckland Grafton Campus. Participants who are either regularly attending GoldFit YMCA exercise training programmes (or who are regularly exercising) and have been so for >12 months, or participants who are not regularly exercising will be invited to participate. Exercise training status adherence (participants who are regularly exercising and/or regularly attending GoldFit YMCA exercise training programmes, or not regularly exercising) will be self-reported, and verified by the 7-day physical activity recall questionnaire detailed below. All participants will undergo an initial visit to the laboratory where screening and familiarisation with all study protocol will take place. This visit will be ~60 minutes duration, and an investigator will explain the nature of the study procedures, answer and questions, and obtain written informed consent from the participant. Anthropometric (height, weight), demographic, general health and 7-day physical activity recall information will be obtained. Once enrolled in the study, participants will be briefly familiarised with the study procedures. To do this, participants will be instrumented for continuous monitoring of heart rate, blood pressure, oxygen saturation and respiration. Brain blood flow will not be measured at this visit. The second visit will be an experimental session. Participants who are already regularly exercising or who are sedentary will attend the laboratory for one experimental visit (~2 hours). The experimental visit will be scheduled ~2-7 days after the initial familiarisation visit. At the experimental session, participants will be asked to sit in a comfortable armchair and remain in that position throughout the session. An intravenous catheter will be positioned in a superficial arm/hand vein, and a venous blood sample obtained (~20mL) by a trained researcher for analysis of blood glucose, cholesterol/lipids, and C-reactive protein. Participants will then be instrumented for continuous monitoring of heart rate, blood pressure, respiration and cerebral blood flow. More specifically, beat-to-beat blood pressure will be measured using finger photoplethysmography, using a small lightweight cuff wrapped around the finger and a cuff wrapped around the upper arm for calibration. Heart rate will be measured using standard electrocardiogram involving the placement of 3 sticky electrodes on the collarbones and chest (standard 3 lead ECG). Participants will wear a mouthpiece and nose clip to monitor respiration. Brain blood flow will be monitored using a transcranial Doppler ultrasound, with a probe placed over the temporal ‘window’ in front of the ear and above the zygomatic arch. The probe will be fixed in place using an adjustable headband and small amount of ultrasound gel. After instrumentation, a 15-minute resting baseline will be observed with the last 5 minutes used for analysis, followed by chemoreflex assessment. Chemoreflex assessment will involve three breathing tests. Tests are separated by a 15-minute rest period. The first test is hyperoxic hypercapnia (CO2 rebreathing), used to evaluate central chemoreflex stimulation with diminished peripheral chemoreflex stimulation). The participant will then be coached using verbal feedback to hyperventilate in room air, until attaining an end tidal carbon dioxide concentration of ~25mmHg. Upon reaching this, the participant will be asked to perform a maximal expiration below functional residual capacity. Upon completion, the inspiratory source will be switched to a rebreathing bag filled with ~95% O2-~5% CO2, and the participant will be instructed to perform 5-6 deep and rapid breaths. Following this, the participant will be instructed to breath as required, until their end tidal carbon dioxide reaches ~55mmHg, signalling the end of the test. The second test is hyperoxia (100% O2), used to evaluate peripheral chemoreflex tonicity. Participants will perform four 1-minute exposures to hyperoxia, separated by 3-5 minutes. The third test is is isocapnic hypoxia (10% O2-90% N2), used to evaluate peripheral chemoreflex stimulation. The exposure will last 5 minutes, with end tidal oxygen of ~45mmHg and end tidal carbon dioxide of ~40mmHg maintained throughout the test.
Sponsors
University of Auckland
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject)
Eligibility
Sex/Gender
All
Age
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
- Aged >60 years old - Men and women - Free of chronic cardiovascular, respiratory, metabolic, or neurological disease - Classified as either: Currently enrolled in the YMCA GoldFit exercise training programme OR have been regularly exercising (3 or more sessions/week) for >12 months, aged >60 years old; Not been regularly exercising for >12 months, aged >60 years old
Exclusion criteria
• BMI <18 kg/m2 • Current smoker • Current users of recreational drugs • Current abusers of alcohol • Recent (<12 month) history of hospital admission • Significant arrhythmias (e.g., atrial fibrillation, previous VT / significant ventricular ectopy) • Hemodynamically significant valvular heart disease (e.g., stenosis, mechanical valve replacement) • Severe left ventricular systolic dysfunction • Recent acute coronary syndrome (<12 months) (e.g., MI, angioplasty, unstable angina) • Previous coronary artery bypass surgery • Secondary causes of hypertension (e.g., phaeochromocytoma) • Recent stroke/TIA (<12 months) • Inability to fully or appropriately provide consent (e.g., language issue, reading capability) • Underlying medical conditions, which in the opinion of the Investigator place the participant at unacceptably high risk for participating in the study. Chronic and systemic illness including: • Severe respiratory disease (e.g., chronic obstructive pulmonary disease); • Severe, uncontrolled type II diabetes; • Current treatment for cancer or complete remission <5 years • Connective tissue or inflammatory disease • Neurological / psychiatric disease (e.g., peripheral neuropathy, dementia, Parkinson’s, epilepsy) • Infection or pyrexial illness • Uncontrolled thyroid disorders • Renal impairment (e.g., eGFR <60) • Liver disease
Outcome results
None listed