Cardiovascular
Conditions
Keywords
Arterial function, Sedentary time, Sex differences, Vasoactive substances
Brief summary
Canadians spend most of their day in sedentary postures (i.e., sitting, lying, reclining). While the beneficial impacts of physical activity on the heart are well-established, less is known about the consequences during time spent in sedentary postures. Currently, we know that spending time in a bout of uninterrupted sitting disrupts blood pressure regulation. However, it is unknown if there are any 'carry over' effects following uninterrupted sitting bouts (i.e., over the next 24-hours). The release of chemicals from arteries controls how stiff or relaxed they are and is important for controlling blood pressure. This is especially true for arteries directly impacted by sitting (e.g., the popliteal artery behind the knee) and that send blood to the brain (e.g., the carotid artery). We have also established that endothelial-derived hyperpolarizing factors (EDHF, chemicals that relax the artery) are important for the relaxation of the artery the popliteal artery. However, we do not know if the effects of EDHFs on this artery are decreased during or after a bout of uninterrupted sitting. A bout of prolonged sitting also causes blood pressure and fluctuations in blood pressure to increase. Importantly, we reported that fluctuations in blood pressure caused by sitting are higher in young males versus females, but average blood pressure was higher among females. These findings suggest that sitting exerts sex differences in the control of blood pressure. Importantly, these effects were only demonstrated during the 2-hour bout of sitting. As such, it is unknown whether blood pressure is negatively impacted after prolonged sitting. The proposed study will determine the impact of EDHFs on blood pressure regulation following a 2-hour bout of prolonged sitting among a group of healthy males and females. Continuous heart rate (via electrocardiogram) and blood pressure (via finger cuff), as well as blood flow from the common carotid artery (in the neck), middle cerebral artery (in the brain) and popliteal artery (behind the knee) will be measured before and after sitting (via ultrasound). The ability of the popliteal artery to relax will be assessed using ultrasound following the release of a pressure cuff. Finally, 24-hour blood pressure and heart rate will be recorded after sitting using a monitor worn for 24-hours. The role of EDHFs will be investigated by comparing 1) baseline blood flow and blood pressure responses (no sitting), 2) blood pressure responses following a 2-hour bout of sitting, and 3) the blood pressure responses following a 2-hour bout of sitting while suppressing the release of EDHFs (via fluconazole ingestion).
Interventions
DRUGPlacebo
Participants will take a placebo sugar pill before and after a bout of prolonged sitting as a control session.
Participants will take 150mg of fluconazole, an EDHF inhibitor before and after a bout of prolonged sitting.
Sponsors
Université de Sherbrooke
Dalhousie University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are between the ages of 18-65. * Have a body mass index of \<40kg/m2 (non-obese). * Have not smoked nicotine or marijuana-containing products most days of the week within the past 6 months. * Have not been diagnosed with a cardiovascular, cerebrovascular, respiratory, or metabolic disease. * Are normotensive. * Are not currently taking any medications for cardiovascular, metabolic, pulmonary, or neurological disorders, or taking sildenafil regularly. * Are not allergic to the adhesive used to secure the activPAL activity monitors. * Are not pregnant or breastfeeding. * Are not regularly taking any of the following: another anti-fungal, heartburn medications containing cisapride (e.g., Propulsid), depression medications containing amitriptyline (e.g., Elavil) or nortriptyline (e.g., Pamelor), erythromycin (antibiotic), lipid lower medications (i.e., statins), non-steroidal anti-inflammatory drugs (e.g., ibuprofen), or vitamin A supplements.
Exclusion criteria
* o Younger than 18 years old. Individuals younger than 18 demonstrate more variable peak FMD responses and require multiple assessments to determine peak response. * Over the age of 65. There are age-related impacts on arterial function and the responses to sitting. * Body mass index of \>40 kg/m2 (i.e., obese II category)(6-8). * Smoked nicotine or marijuana-containing products most days of the week within the past 6 months. Cardiovascular health for participants who smoke is poor compared to those who do not smoke, which will negatively impact our arterial function outcomes. * Have been diagnosed with a cardiovascular, cerebrovascular, respiratory, or metabolic disease. Such conditions impact our assessments of arterial health. The results of unhealthy participants are not of interest in this study. * Hypertension (seated resting systolic pressure \>139 mmHg and/or diastolic pressure \>89 mmHg). Hypertensive individuals have impairments in artery health, which will affect their baseline artery health measures. * Hypotensive (seated resting systolic pressure \<90 mmHg and/or diastolic pressure \<60 mmHg). Hypotensive people are more likely to experience further reductions in blood pressure during the sitting protocol, which will increase the risk of fainting and/or dizziness. * Have a history of fainting and/or dizziness during sitting or standing. * Prescribed medications for cardiovascular, metabolic, pulmonary, or neurological disorders. This includes people using hormone replacement therapy. These medications will interfere with our assessments and interpretation of arterial health. * Have a known allergy to the clear medical adhesive used to secure the activPAL activity monitors. * Females who are pregnant or breastfeeding. Pregnant and breastfeeding females are ineligible to participate. This is due to the known increases in arterial vasodilation associated with pregnancy related sex hormones. * Currently or recently (within the past 6 months) regularly taking sildenafil or other medications that increase the relaxing effects of nitric oxide in arteries. Such medication will influence artery blood flow and flow-mediated dilation responses. * Are regularly taking any of the following: another anti-fungal, heartburn medications containing cisapride (e.g., Propulsid), depression medications containing amitriptyline (e.g., Elavil) or nortriptyline (e.g., Pamelor), erythromycin (antibiotic), lipid lower medications (i.e., statins), non-steroidal anti-inflammatory drugs (e.g., ibuprofen), or vitamin A supplements. These are to minimize the chance of a participant experiencing an adverse reaction to the fluconazole tablet.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Popliteal Low-Flow Mediated Constriction | Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting | During a period of distal cuff-induced ischemia, the endothelial-dependent vasoconstrictor response will be assessed via Duplex ultrasonography. The popliteal artery will be imaged slightly above the popliteal fossa. The L-FMC response will be quantified as the percent reduction in arterial diameter from baseline to the nadir diameter from the last 30-s of a 5-min distal cuff occlusion period. |
| Acute Blood Pressure | Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. | Beat-by-beat systolic (SBP) and diastolic (DBP) blood pressure will be measured using finger photoplethysmography for 20 minutes before the bout of prolonged sitting, 20 minutes after 1-hour of sitting, and 20 minutes after 2-hours of sitting. Mean arterial pressure will be quantified as 1/3 SBP + 2/3 DBP. |
| Ambulatory Blood Pressure | This will be worn for a 24-hour period before the first prolonged sitting session, and for 24-hours after each bout of prolonged sitting. | Using an ABPMpro Ambulatory Blood Pressure Monitors, habitual blood pressure will be measured every 20-minutes during waking hours, and every 30-minutes during sleeping hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Carotid Artery Blood Flow Velocity | Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. | Blood flow velocity will be measured immediately prior to the bifurcation in the common carotid artery using Duplex ultrasonography for 5 minutes. |
| Middle Cerebral Artery Velocity | Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. | Blood flow velocity will be measured via transcranial Doppler over the trans-temporal window for 5 minutes. |
| Popliteal Flow Mediated Dilation (FMD) | Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. | Following a period of distal cuff induced ischemia, the endothelial-dependent vasodilator response will be assessed via Duplex ultrasonography. The popliteal artery will be imaged slightly above the popliteal fossa. The FMD response will be quantified as the percent increase in arterial diameter from baseline to the peak diameter following the release of the distal cuff. |
| Physical Activity Behaviour Questionnaire | At time of study enrolment | A subjective questionnaire that provides information regarding habitual physical activity and sedentary behaviours. |
| Heart Rate Variability (HRV) | Acute: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. Ambulatory: 24-hours at baseline, 24-hours after each bout of prolonged sitting. | Heart rate will be determined using cardiac intervals from a lead II electrocardiography during prolonged sitting, and from the built-in electrocardiogram in the ambulatory blood pressure monitor. HRV will be derived from these waveforms using an offline HRV analysis module. Time-domain (I.e., RMSSD), frequency-domain, low frequency (LF) power, high frequency (HF) power, and the LF/HF ratio will be quantified for each participant. |
| Carotid Intima Media Thickness (cIMT) | Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. | cIMT will be determined from a 5-minute recording of the carotid artery, imaged prior to the bifurcation using Duplex ultrasonography. |
| Carotid Artery Distensibility | Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. | Distensibility will be determined from 5-minutes of recorded carotid artery imaging via Duplex ultrasonography, and will be calculated as the difference between average arterial diameter during systole and diastole. |
| Blood Pressure Varibility (BPV) | Acute: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. Ambulatory: 24-hours at baseline, 24-hours after each bout of prolonged sitting. | Beat-by-beat BPV during sitting will be quantified using the blood pressure measurements derived from finger photoplethysmography. This will be calculated as the average absolute difference between successive finger blood pressure measurements, for systolic blood pressure, diastolic blood pressure, and mean arterial pressure. Ambulatory BPV will be quantified from the 24-hour blood pressure monitors. |
| Cardiovagal Baroreflex Sensitivity (cvBRS) | Before prolonged sitting, after 1 hour of sitting, after 2-hours of sitting. | cvBRS will be quantified from beat-by-beat systolic blood pressure (SBP) and R-R intervals in a cvBRS software. cvBRS outcomes will be quantified from a minimum of 3 sequences in which beat-by-beat SBP changes were ≥1 mmHg and changes in R-R interval were ≥ 1 ms. Overall cvBRS is represented by the average slope of SBP and R-R interval regressions for the pooled sequences, and reported separately for both up and down sequences. Baroreflex effectiveness index (BEI) will be measured as the ratio of the number of SBP ramp-induced changes in RR interval to the total number of SBP ramps observed. This will be reported separately for both up and down sequences. This will be measured over a 20-minute time period. |
| Habitual Activity & Postures | Before first bout of sitting, after each bout of sitting. | Habitual activity and postures will be measured using activPAL inclinometer-accelerometers positioned on the torso, thigh, and calf. Monitors will be waterproofed and attached 24-hr/day for 8 days via clear medical adhesive. Physical activity (step counts, physical activity intensity), upright posture and detailed sedentary postures (e.g., sitting versus lying time) will be determined via validated, custom software that was developed and openly published by our group. |
| Baseline Arterial Diameters | Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. | Arterial diameter of the popliteal and carotid arteries will be determined via Duplex ultrasonography over a minimum of 2-minutes. |
Countries
Canada
Contacts
CONTACTMolly K Courish, MSc, PhD(s)
PRINCIPAL_INVESTIGATORMyles W O'Brien, PhD
Université de Sherbrooke
Outcome results
None listed