A 5-Week Guided Active Play Program Modulates Skin Microvascular Reactivity in Healthy Children.

PURPOSE: Children's poor levels of physical activity (PA) participation and early-onset vascular aging are identified as global health challenges. Children's guided activity play (GAP)-based PA programs have emerged as effective strategies to improve cardiovascular risk factors and health-related fitness. This study proposes to investigate whether GAP improves children's cutaneous microvascular reactivity and health-related fitness. METHODS: Children's (n = 18; 9.8 [1.5] y) PA during a 5-week (4 d/wk; 1 h/d) GAP program was assessed (accelerometry) with preassessments and postassessments for anthropometric, musculoskeletal fitness, blood pressure, estimated aerobic power, and cutaneous microvascular reactivity. RESULTS: PA averaged 556 (132) kcal·week-1 at 34.7% (7.5%) time at moderate to vigorous intensity. Resting heart rate (-9.5%) and diastolic blood pressure (-7.8%) were reduced without changes in health-related fitness indices. Cutaneous microvascular reactivity to sodium nitroprusside iontophoresis increased the average perfusion (+36.8%), average cutaneous vascular conductance (+30%), the area under the curve (+28.8%), and a faster rise phase (+40%) of perfusion (quadratic modeling; P ≤ .05). Chi-square and crosstabulation analysis revealed significant association between children's PA levels and sodium nitroprusside average perfusion levels, where children with PA levels ≥205.1 kcal.55 minute-1 were overrepresented in the medium/high levels of sodium nitroprusside perfusion. CONCLUSION: A 5-week GAP modified the microvascular reactivity in children without changes in body mass, musculoskeletal fitness, or estimated aerobic power.

A Measure of Caregivers' Distress-Promoting Behaviors During Toddler Vaccination: Validation of the OUCHIE-RV.

OBJECTIVE: The current study discusses the development and preliminary validation of an observational measure of caregivers' distress-promoting behavior (OUCHIE-RV) in the context of toddler routine vaccination. METHODS: Measure validation was based on a sample of caregiver-toddler dyads (N = 223) from a longitudinal cohort-sequential study who were observed during toddlers' 12-, 18-, or 24-month routine vaccinations. Validity was assessed using correlations and cross-lagged path analysis and associations were tested between OUCHIE-RV composite scores and toddlers' pain-related distress as well as caregivers' state anxiety, soothing behaviors, heart rate, and heart rate variability. Interrater reliability was examined using intraclass correlations (ICC) and kappa coefficients. RESULTS: Results of a cross-lagged path analysis indicated positive concurrent (ß = .27 to ß = .37) and cross-lagged predictive associations (ß = .01 to ß = .34) between OUCHIE-RV composite scores (reflecting the frequency and intensity of caregivers' distress-promoting behavior) and toddlers' pain-related distress. OUCHIE-RV composite scores were negatively associated with caregivers' concurrent use of physical comfort (r = -.34 to -.24) and rocking (r = -.36 to -.19) and showed minimal associations with caregivers' use of verbal reassurance (r = .06 to .12), state anxiety (r = -.02 to r = .09), heart rate (r = -.15 to r = .05), and heart rate variability (r = -.04 to r = .13). Interrater reliability was strong (Cohen's k = .86 to .97, ICC = .77 to .85). CONCLUSIONS: Findings provide support for the validity and reliability of the OUCHIE-RV as a research tool for measuring caregiver behaviors that promote toddlers' pain-related distress during routine vaccinations and contribute to a better understanding of the dynamics of caregiver-toddler interaction in acute pain contexts.

Cardiovascular and autonomic responses to passive arm or leg movement in men and women.

PURPOSE: Women display an attenuated mechanoreflex during leg movement; however, sex differences in the response to arm movement are unknown. METHODS: Men (n = 12) and women (n = 10) performed passive arm or leg movement where either the right elbow or right knee was passively flexed/extended for 3 min at 30 times/min. Mean arterial pressure (MAP), cardiac output index (Qi), and heart rate (HR) were continuously measured and 1-min averages along with peak values were obtained. Heart rate variability was measured at baseline and throughout 3 min of passive movement. RESULTS: Men had a greater average HR (P = 0.006) and Qi (P = 0.05) responses to passive limb movement compared to women. Men also had a greater (P = 0.02) and faster (P = 0.04) peak Qi response compared to women. During arm movement, men exhibited a greater change of average MAP compared to both women (P = 0.002) and leg movement (P = 0.05). Movement of either limb in both sexes decreased low-frequency power (LF; P = 0.04), decreased low-frequency to high-frequency ratio (LF/HF; P = 0.03), and increased high-frequency power (HF; P = 0.01) of heart rate variability. Women had lower pulse wave velocity (P = 0.02), higher root mean square of the successive differences (RMSSD; P = 0.04), lower LF power (P = 0.04), higher HF power (P = 0.03), and higher cardiovagal baroreceptor sensitivity (P = 0.003) compared to men at all time points. CONCLUSIONS: We have found sex- and limb-dependent responses where men exhibit higher blood pressure in response to passive arm movement compared to women and compared to leg movement.

Influence of sex, menstrual cycle, and oral contraceptives on the cerebrovascular response to paced deep breathing.

PURPOSE: Deep breathing assesses autonomic function; however, many researchers/clinicians do not account for hyperventilation, brain blood flow or blood pressure. METHODS: Men and women (with/without oral contraceptives) participated. women participated during low and high hormone phases of the menstrual cycle. Blood pressure, end-tidal carbon dioxide, middle cerebral artery velocity and cerebrovascular resistance were assessed. RESULTS: Deep breathing decreased end-tidal carbon dioxide and middle cerebral artery velocity while increasing cerebrovascular resistance in all participants; blood pressure decreased in men. There were no influences of menstrual cycle or oral contraceptives. CONCLUSIONS: Men have different autonomic responses to deep breathing compared to women.

Assessing cerebrovascular autoregulation from critical closing pressure and resistance area product during upright posture in aging and hypertension.

Static cerebral autoregulation (sCA) is believed to be resistant to aging and hypertensive pathology. However, methods to characterize autoregulation commonly rely on beat-by-beat mean hemodynamic measures and do not consider within-beat pulse wave characteristics that are impacted by arterial stiffening. We examined the role of critical closing pressure (CrCP) and resistance area product (RAP), two measures derived from the pulse wave, across supine lying, sitting, and standing postures in young adults, normotensive older adults, and older adults with controlled and uncontrolled hypertension (N = 80). Traditional measures of sCA, using both intracranial and extracranial methods, indicated similar efficiency across all groups, but within-beat measures suggested different mechanisms of regulation. At rest, RAP was increased in hypertension compared with young adults (P < 0.001), but CrCP was similar. In contrast, the drop in CrCP was the primary regulator of change in cerebrovascular resistance upon adopting an upright posture. Both CrCP and RAP demonstrated group-by-posture interaction effects (P < 0.05), with older hypertensive adults exhibiting a rise in RAP that was absent in other groups. The posture-related swings in CrCP and RAP were related to changes in both the pulsatile and mean components of arterial pressure, independent of age, cardiac output, and carbon dioxide. Group-by-posture differences in pulse pressure were mediated in part by an attenuated heart rate response in older hypertensive adults (P = 0.002). Examination of pulsatile measures in young, elderly, and hypertensive adults identified unique differences in how cerebral blood flow is regulated in upright posture.

Machine learning algorithms for detection of visuomotor neural control differences in individuals with PASC and ME.

The COVID-19 pandemic has affected millions worldwide, giving rise to long-term symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) infection, colloquially referred to as long COVID. With an increasing number of people experiencing these symptoms, early intervention is crucial. In this study, we introduce a novel method to detect the likelihood of PASC or Myalgic Encephalomyelitis (ME) using a wearable four-channel headband that collects Electroencephalogram (EEG) data. The raw EEG signals are processed using Continuous Wavelet Transform (CWT) to form a spectrogram-like matrix, which serves as input for various machine learning and deep learning models. We employ models such as CONVLSTM (Convolutional Long Short-Term Memory), CNN-LSTM, and Bi-LSTM (Bidirectional Long short-term memory). Additionally, we test the dataset on traditional machine learning models for comparative analysis. Our results show that the best-performing model, CNN-LSTM, achieved an accuracy of 83%. In addition to the original spectrogram data, we generated synthetic spectrograms using Wasserstein Generative Adversarial Networks (WGANs) to augment our dataset. These synthetic spectrograms contributed to the training phase, addressing challenges such as limited data volume and patient privacy. Impressively, the model trained on synthetic data achieved an average accuracy of 93%, significantly outperforming the original model. These results demonstrate the feasibility and effectiveness of our proposed method in detecting the effects of PASC and ME, paving the way for early identification and management of the condition. The proposed approach holds significant potential for various practical applications, particularly in the clinical domain. It can be utilized for evaluating the current condition of individuals with PASC or ME, and monitoring the recovery process of those with PASC, or the efficacy of any interventions in the PASC and ME populations. By implementing this technique, healthcare professionals can facilitate more effective management of chronic PASC or ME effects, ensuring timely intervention and improving the quality of life for those experiencing these conditions.

Heart failure clinic inclusion and exclusion criteria: cross-sectional study of clinic's and referring provider's perspectives.

OBJECTIVES: There are substantial variations in entry criteria for heart failure (HF) clinics, leading to variations in whom providers refer for these life-saving services. This study investigated actual versus ideal HF clinic inclusion or exclusion criteria and how that related to referring providers' perspectives of ideal criteria. DESIGN, SETTING AND PARTICIPANTS: Two cross-sectional surveys were administered via research electronic data capture to clinic providers and referrers (eg, cardiologists, family physicians and nurse practitioners) across Canada. MEASURES: Twenty-seven criteria selected based on the literature and HF guidelines were tested. Respondents were asked to list any additional criteria. The degree of agreement was assessed (eg, Kappa). RESULTS: Responses were received from providers at 48 clinics (37.5% response rate). The most common actual inclusion criteria were newly diagnosed HF with reduced or preserved ejection fraction, New York Heart Association class IIIB/IV and recent hospitalisation (each endorsed by >74% of respondents). Exclusion criteria included congenital aetiology, intravenous inotropes, a lack of specialists, some non-cardiac comorbidities and logistical factors (eg, rurality and technology access). There was the greatest discordance between actual and ideal criteria for the following: inpatient at the same institution (κ=0.14), congenital heart disease, pulmonary hypertension or genetic cardiomyopathies (all κ=0.36). One-third (n=16) of clinics had changed criteria, often for non-clinical reasons. Seventy-three referring providers completed the survey. Criteria endorsed more by referrers than clinics included low blood pressure with a high heart rate, recurrent defibrillator shocks and intravenous inotropes-criteria also consistent with guidelines. CONCLUSIONS: There is considerable agreement on the main clinic entry criteria, but given some discordance, two levels of clinics may be warranted. Publicising evidence-based criteria and applying them systematically at referral sources could support improved HF patient care journeys and outcomes.

The association between shift work exposure and cognitive impairment among middle-aged and older adults: Results from the Canadian Longitudinal Study on Aging (CLSA).

BACKGROUND: Shift work, especially rotating and night shift work, has been linked to a wide range of detrimental health outcomes. Occupational factors like shift work and their potential impact on cognitive functions have received little attention, and the evidence is inconclusive. The objective of our study is to explore associations between shift work exposure and cognitive impairment indicators based on comparisons with the normative standards from the Canadian population. METHODS: Cross-sectional analyses were performed using baseline Canadian Longitudinal Study on Aging database, including 47,811 middle-aged and older adults (45-85 years). Three derived shift work variables were utilized: ever exposed to shift work, shift work exposure in longest job, and shift work exposure in current job. Four cognitive function tests were utilized, Rey Auditory Verbal Learning Tests (immediate and delayed) representing memory domain, and Animal Fluency, and Mental Alteration, representing the executive function domain. All cognitive test scores included in study were normalized and adjusted for the participant's age, sex, education and language of test administration (English and French), which were then compared to normative data to create "cognitive impairment' variables. Unadjusted and adjusted multivariable logistic regression models were used to determine associations between shift work variables and cognitive impairment individually (memory and executive function domains), and also for overall cognitive impairment. RESULT: Overall, one in every five individuals (21%) reported having been exposed to some kind of shift work during their jobs. Exposure to night shift work (both current and longest job) was associated with overall cognitive impairment. In terms of domain-based measures, night shift work (longest job) was associated with memory function impairment, and those exposed to rotating shift work (both current and longest job) showed impairment on executive function measures, when compared to daytime workers. CONCLUSION: This study suggests disruption to the circadian rhythm, due to shift work has negative impact on cognitive function in middle-aged and older adults and this warrants further investigation.

Parents' physiological reactivity to child distress and associations with parenting behaviour: A systematic review.

This systematic review and narrative synthesis characterized parents' physiological stress responses to child distress and how parents' physiological and behavioural responses relate. The review was pre-registered with PROSPERO (#CRD42021252852). In total, 3607 unique records were identified through Medline, Embase, PsycINFO, and CINAHL. Fifty-five studies reported on parents' physiological stress responses during their young child's (0-3 years) distress and were included in the review. Results were synthesized based on the biological outcome and distress context used and risk of bias was evaluated. Most studies examined cortisol or heart rate variability (HRV). Small to moderate decreases in parents' cortisol levels from baseline to post-stressor were reported across studies. Studies of salivary alpha amylase, electrodermal activity, HRV, and other cardiac outcomes reflected weak or inconsistent physiological responses or a paucity of relevant studies. Among the studies that examined associations between parents' physiological and behavioural responses, stronger associations emerged for insensitive parenting behaviours and during dyadic frustration tasks. Risk of bias was a significant limitation across studies and recommendations for future research are discussed.

The association of objectively and subjectively measured physical activity and sedentary time with prediabetes and type 2 diabetes in adults: a cross-sectional study in Framingham Heart Study cohorts.

The purpose of this study was to examine whether using both objectively (accelerometer) and subjectively (questionnaire) measured moderate- to vigorous-intensity physical activity (MVPA) and sedentary time (SED) improves the prediction of prediabetes and type 2 diabetes (pre/T2D) using data from the Framingham Heart Study (n = 4200). Logistic regression was used to examine the odds ratio of pre/T2D in groups cross-classified by subjective and objective MVPA and SED. Less than half of participants fell into concordant categories of MVPA and SED using subjective and objective measures, with 7.0%-9.4% of participants in the extreme discordant categories of high-low or low-high subjective-objective MVPA or SED. Low objective MVPA, regardless of subjective MVPA status, was associated with a higher prevalence of pre/T2D (P < 0.05). When cross-classifying by MVPA and SED, the majority of participants fell into concordant categories of MVPA-SED, with <4% of participants in the extreme discordant categories of MVPA-SED. Low objective MVPA, regardless of objective SED, was associated with a higher prevalence of pre/T2D (P < 0.05). These findings suggest that low objectively measured MVPA appears more closely associated with pre/T2D risk compared with subjective measures, and there does not appear to be an additive effect of SED on pre/T2D risk after accounting for MVPA.

The association between shift work exposure and the variations in age at natural menopause among adult Canadian workers: results from the Canadian Longitudinal Study on Aging (CLSA).

OBJECTIVE: A wide range of negative health outcomes have been associated with shift work (SW) particularly night and rotating SW. However, little is known about effects of SW exposure on reproductive health outcomes. The objective of our study is to prospectively investigate the association between SW exposure and the variations in age at natural menopause among adult Canadian workers. METHODS: Secondary data analyses were performed using the Canadian Longitudinal Study on Aging database. Premenopausal women (N = 3,688) at baseline were followed prospectively for 3 years. Three derived variables were used to measure SW primary exposure: 1) ever exposed to SW, 2) SW exposure in current job, and 3) SW exposure in the longest job. Cox proportional hazard regression models were used to evaluate risk of variations in age at natural menopause after adjusting for potential confounders. RESULT: One out of five women (20%) reported to be ever exposed to SW during their jobs. Overall, women who were ever exposed to SW were significantly associated with a delayed onset of menopause compared with daytime workers (hazard ratios [HR] = 0.77, 95% CI, 0.61-0.98). Particularly, when compared with daytime workers, rotating shift worker in the current and longest job were significantly related to delayed onset of menopause (HR = 0.64, 95% CI, 0.46-0.89 and HR = 0.65, 95% CI, 0.49-0.86), respectively. CONCLUSION: Our results suggest a relationship between rotating shift and delayed onset of menopause. We speculate that disruptive circadian stimuli may play a role in menopausal onset and this warrants further investigation.Video Summary:http://links.lww.com/MENO/A940 .

Effect of Upright Posture on Endothelial Function in Women and Men.

Women are more prone to orthostatic intolerance compared to men and have a greater vasodilatory capacity. We investigated the hypothesis that women would have greater peripheral flow-mediated dilation (FMD) while in the upright posture compared to men, which could contribute to this phenomenon. In young healthy women (age: 20 ± 3, BMI: 27 ± 5 kg/m2, n = 10) and men (age = 21 ± 2, BMI: 27 ± 8 kg/m2, n = 8), we assessed FMD of the brachial artery and hemodynamics to determine endothelial function during the supine and 70° head-up tilt postures (randomized). The brachial artery was kept at heart level in both trials. We observed that FMD increased in both sexes during tilt (Women: 11.9 ± 5.3 to 15.7 ± 5.6%; Men: 8.4 ± 3.2 to 14.6 ± 3.4%, Main effect of tilt p = 0.005) which was not due to changes in blood pressure or shear stress. There were no interaction effects between sex and posture. In a second cohort of women (age: 22 ± 3, BMI: 23 ± 3 kg/m2, n = 9) and men (age: 22 ± 2, BMI: 25 ± 8 kg/m2, n = 8), we investigated reactive hyperemia by peripheral arterial tonometry (LnRHI) via EndoPAT. Interestingly, we found that the EndoPAT response was decreased in both sexes during tilt (LnRHI: Men: 0.70 ± 0.28 to 0.59 ± 0.40, Women: 0.52 ± 0.23 to 0.30 ± 0.32, Main effect of tilt p = 0.037). We previously found that FMD is related to coronary responses to acetylcholine and adenosine whereas EndoPAT is related to coronary responses to dobutamine. Therefore, we suggest that sympathetic mediated dilation is attenuated in the upright posture while the increased vasodilatory response as measured by FMD in the tilt posture could be attributed to increasing metabolite production from postural muscles.

Menstrual cycle and oral contraceptives influence cerebrovascular dynamics during hypercapnia.

Women experience fluctuating orthostatic intolerance during the menstrual cycle, suggesting sex hormones may influence cerebral blood flow. Young (aged 18-30) healthy women, either taking oral contraceptives (OC; n = 14) or not taking OC (NOC; n = 12), were administered hypercapnic gas (5%) for 5 min in the low hormone (LH; placebo pill) and high hormone (HH; active pill) menstrual phases. Hemodynamic and cerebrovascular variables were continuously measured. Cerebral blood velocity changes were monitored using transcranial doppler ultrasound of the middle cerebral artery to determine cerebrovascular reactivity. Cerebral autoregulation was assessed using steady-state analysis (static cerebral autoregulation) and transfer function analysis (dynamic cerebral autoregulation; dCA). In response to hypercapnia, menstrual phase did not influence static cardiovascular or cerebrovascular responses (all p > 0.07); however, OC users had a greater increase of mean middle cerebral artery blood velocity compared to NOC (NOC-LH 12 ± 6 cm/s vs. NOC-HH 16 ± 9 cm/s; OC-LH 18 ± 5 cm/s vs. OC-HH 17 ± 11 cm/s; p = 0.048). In all women, hypercapnia improved high frequency (HF) and very low frequency (VLF) cerebral autoregulation (decreased nGain; p = 0.002 and <0.001, respectively), whereas low frequency (LF) Phase decreased in NOC-HH (p = 0.001) and OC-LH (p = 0.004). Therefore, endogenous sex hormones reduce LF dCA during hypercapnia in the HH menstrual phase. In contrast, pharmaceutical sex hormones (OC use) have no acute influence (HH menstrual phase) yet elicit a chronic attenuation of LF dCA (LH menstrual phase) during hypercapnia.

Ventilatory response to hypercapnia is increased after 4 h of head down bed rest.

Head-down bed rest (HDBR) has previously been shown to alter cerebrovascular and autonomic control. Previous work found that sustained HDBR (≥ 20 days) attenuates the hypercapnic ventilatory response (HCVR); however, little is known about shorter-term effects of HDBR nor the influence of HDBR on the hypoxic ventilatory response (HVR). We investigated the effect of 4-h HDBR on HCVR and HVR and hypothesized attenuated ventilatory responses due to greater carotid and brain blood flow. Cardiorespiratory responses of young men (n = 11) and women (n = 3) to 5% CO2 or 10% O2 before and after 4-h HDBR were examined. HDBR resulted in lower HR, lower cardiac output index, lower common carotid artery flow, higher SpO2, and higher pulse wave velocity. After HDBR, tidal volume and ventilation responses to 5% CO2 were enhanced (all P < 0.05), yet no other changes in cardiorespiratory variables were evident. There was no influence of HDBR on the cardiorespiratory responses to hypoxia (all P > 0.05). Short-duration HDBR does not alter the HVR, yet enhances the HCVR, which we hypothesize is a consequence of cephalic CO2 accumulation from cerebral congestion.

Standard exercise stress testing attenuates peripheral microvascular function in patients with suspected coronary microvascular dysfunction.

BACKGROUND: The effect of exercise on the microvasculature of patients with suspected coronary microvascular dysfunction (CMD), assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT; EndoPAT), is unknown. The present study aimed to determine if standard clinical exercise stress testing (GXT) affected peripheral microvascular function, as determined by the reactive hyperemia index (RHI and LnRHI), in patients with suspected CMD. METHODS: In a cross-sectional study, patients (n = 76) were grouped based on whether the GXT was performed; 1) prior to (exercisers; n = 30), or 2) after the vascular assessment (non-exercisers; n = 46). Patients with an adenosine index of microvascular resistance > 25, adenosine coronary flow reserve (CFR) < 2.0, and/or acetylcholine CFR < 1.5 were considered to have CMD (n = 42). RHI and LnRHI quantified finger pulse amplitude hyperemia following 5 min of forearm ischemia. RESULTS: LnRHI was lower in patients with CMD compared to patients without CMD, while LnRHI was also lower in exercisers compared to non-exercisers (LnRHI: CMD Non-Exercisers: 0.63 ± 0.25; CMD Exercisers: 0.54 ± 0.19; No CMD Non-Exercisers: 0.85 ± 0.23; No CMD Exercisers: 0.63 ± 0.26; Condition and Exercise Main Effects: Both P < 0.01). In patients who did not exercise prior to the vascular assessment, the receiver operating characteristic curve (ROC) for LnRHI to predict CMD was 0.76 (95% CI: 0.62-0.91; P < 0.01). However, in patients who performed exercise prior to the vascular assessment, the ROC for LnRHI to predict CMD was 0.60 (95% CI: 0.40-0.81; P = 0.34). CONCLUSIONS: CMD is associated with impaired peripheral microvascular function and preceding acute exercise is associated with further reductions of LnRHI. Further, acute exercise abolished the capacity for RH-PAT to predict the presence of CMD in patients with chest pain and non-obstructive coronary arteries. RH-PAT measurements in patients with suspected CMD should not be conducted after exercise has been performed.

Characterization of the Human Coronary Microvascular Response to Multiple Hyperaemic Agents.

BACKGROUND: It is unclear whether the coronary microvascular responses to multiple, mechanistically distinct hyperaemic agents exert similar dilatory responses or share common clinical predictors. This study therefore sought to characterize the index of microvascular resistance (IMR) response to multiple hyperaemic agents in the human coronary circulation. METHODS: Thermodilution-derived IMR was determined during intravenous adenosine, intracoronary acetylcholine, and intravenous dobutamine in patients with ischemic symptoms and nonobstructive coronary angiograms. A total of 128 patients were studied (44 with adenosine and acetylcholine, and 84 with all agents). Adenosine IMR >25, acetylcholine IMR >31, and dobutamine IMR >29 were used to define elevated responses. RESULTS: IMR responses demonstrated weak-to-moderate association (adenosine vs acetylcholine IMR: ρ = 0.33; adenosine vs dobutamine IMR: ρ = 0.51; acetylcholine vs dobutamine IMR: ρ = 0.28; all P < 0.01). Logistic regression analyses revealed that: (1) elevated adenosine IMR was associated with increasing age and left ventricle hypertrophy (odds ratio [OR] = 1.27 and 1.58; both P < 0.05, respectively), (2) elevated acetylcholine IMR was associated with increasing plasma uric acid (OR = 1.09; P < 0.05), and (3) elevated dobutamine IMR was associated with hypertension and left atrial volume index (OR = 3.99 and 1.07; both P < 0.05, respectively). Subset analyses to evaluate clinical utility of the acetylcholine and dobutamine IMR, independent of abnormal adenosine IMR, revealed that elevated acetylcholine and/or dobutamine IMR were associated with higher risk exercise stress tests, left atrial volumes, and burden of exertional chest pain. CONCLUSIONS: Microvascular-specific IMR responses to different hyperaemic agents are only moderately associated, whereas the predictors for agent-specific IMR responses varied, suggesting that multiple pharmacologic agents interrogate different microvascular control mechanisms.

CONTEXTE: On ne sait pas vraiment si les réponses microvasculaires coronariennes à de multiples agents hyperémiques aux modes d'action distincts ont des effets vasodilatateurs similaires ou partagent des facteurs prédictifs cliniques communs. Cette étude visait donc à caractériser la réponse selon l'indice de résistance microvasculaire (IMR) aux multiples agents hyperémiques dans la circulation coronarienne chez l'humain. MÉHODOLOGIE: L'IMR obtenu par thermodilution a été déterminé pendant l'administration intraveineuse d'adénosine, intracoronarienne d'acétylcholine et intraveineuse de dobutamine chez des patients présentant des symptômes ischémiques et par angiogrammes coronariens non obstructifs. Un total de 128 patients (44 avec l'adénosine et l'acétylcholine, et 84 avec tous les agents) ont fait partie de l'étude. Des réponses élevées étaient définies par un IMR à l'adénosine > 25, un IMR à l'acétylcholine > 31 et un IMR à la dobutamine > 29. RÉSULTATS: Les réponses selon l'IMR ont révélé une association faible à modérée (IMR à l'adénosine vs IMR à l'acétylcholine : ρ = 0,33; IMR à l'adénosine vs IMR à la dobutamine : ρ = 0,51; IMR à l'acétylcholine vs IMR à la dobutamine : ρ = 0,28; tous : p < 0,01). Des analyses de régression logistique ont révélé que : 1) un IMR à l'adénosine élevé était associé à l'avancement en âge et à une hypertrophie ventriculaire gauche (rapport des cotes [RC] = 1,27 et 1,58; p < 0,05 respectivement pour les deux), 2) un IMR à l'acétylcholine élevé était associé à l'augmentation de la concentration plasmatique d'acide urique (RC = 1,09; p < 0,05) et 3) un IMR à la dobutamine élevé était associé à l'hypertension et à l'indice de volume auriculaire gauche (RC = 3,99 et 1,07; p < 0,05 respectivement pour les deux). Des analyses par sous-groupes visant à évaluer l'utilité clinique de l'IMR à l'acétylcholine et à la dobutamine, indépendamment d'un IMR à l'adénosine anormal, ont révélé que des IMR à l'acétylcholine et/ou à la dobutamine élevés étaient associés à une augmentation du risque lors des épreuves à l'effort, à un volume auriculaire gauche plus élevé et à une augmentation du fardeau associé à la douleur thoracique à l'effort. CONCLUSIONS: Les réponses microvasculaires selon l'IMR à différents agents hyperémiques sont seulement modérément associées, alors que les facteurs prédictifs des réponses selon l'IMR spécifique de l'agent varient, ce qui laisse croire que les multiples agents pharmacologiques font appel à différents mécanismes de contrôle microvasculaire.

Sex differences in the autonomic and cerebrovascular responses to upright tilt.

Sex differences in the regulation of autonomic and cerebrovascular responses to orthostatic stress remain unclear. The objectives of this study were to concurrently investigate autonomic control and cerebrovascular resistance indices, including critical closing pressure (CrCP) and resistance area product (RAP), during upright tilt in men and women. In 13 women and 14 men (18-29 years), ECG, non-invasive blood pressure, middle cerebral artery blood velocity, and end-tidal CO2 (ETCO2) were continuously measured during supine rest and 70° tilt. Heart rate variability (HRV), cardiovagal baroreflex sensitivity (cBRS), and transfer function parameters of dynamic cerebral autoregulation were calculated. Compared to supine, upright tilt increased the low frequency-to-high frequency ratio of HRV in men only (P = 0.044), and decreased cBRS more in women (P = 0.001). Cerebrovascular resistance index (CVRi) increased during tilt only in men (sex-by-time interaction: P = 0.004). RAP was lower in women throughout tilt (main effect of sex: P = 0.022). CrCP decreased during tilt in both sexes (main effect of time: P < 0.001). Normalizing to ETCO2 did not alter the effect of tilt on cerebrovascular resistance. Men displayed a greater increase of sympathetic indices and CVRi during tilt while women had greater parasympathetic withdrawal. We hypothesize that increased sympathetic activity in men may drive sex differences in the cerebrovascular response to upright posture.

Oral contraceptives and menstrual cycle influence autonomic reflex function.

Progesterone and its analogues are known to influence ventilation. Therefore, the purpose of this study was to investigate the role of endogenous and pharmaceutical female sex hormones in ventilatory control during the activation of the metaboreflex, mechanoreflex, and CO2 chemoreflex. Women aged 18-30 taking (n = 14) or not taking (n = 12) oral contraceptives (OC and NOC, respectively) were tested in the low hormone (LH) and high hormone (HH) conditions corresponding to the early follicular and mid-luteal phases (NOC) or placebo and high-dose pills (OC). Women underwent three randomized trials: (a) 3 min of passive leg movement (PLM), (b) 2 min of 40% maximal voluntary handgrip exercise followed by 2 min of post-exercise circulatory occlusion (PECO), and (c) 5 min of breathing 5% CO2 . We primarily measured hemodynamics and ventilation. During PLM, the OC group had a smaller pressor response (p = .012). During PECO, the OC group similarly exhibited a smaller pressor response (p = .043) and also exhibited a greater ventilatory response (p = .024). Lastly, in response to breathing 5% CO2 , women in the HH phase had a greater ventilatory response (p = .022). We found that OC use attenuates the pressor response to both the metaboreflex and mechanoreflex while increasing the ventilatory response to metaboreflex activation. We also found evidence of an enhanced CO2 chemoreflex in the HH phase. We hypothesize that OC effects are from the chronic upregulation of pulmonary and vascular ß-adrenergic receptors. We further suggest that the increased cyclic progesterone in the HH phase enhances the chemoreflex.

Effect of a neck compression collar on cardiorespiratory and cerebrovascular function in postural orthostatic tachycardia syndrome (POTS).

Postural orthostatic tachycardia syndrome (POTS) is accompanied by reduced brain blood flow, autonomic dysfunction, and orthostatic intolerance. We hypothesized that wearing a neck compression collar would attenuate orthostatic symptoms, increase brain blood flow, and influence autonomic reflexes. Ten participants with POTS (9 women, age: 36 ± 10) underwent two trials of supine rest, paced deep breathing (6 breaths/min), Valsalva maneuver (40 mmHg for 15 s), and 70° upright tilt. For one trial, participants wore a neck compression device (Q30 Innovations). Blood pressure, heart rate (HR), brain blood flow velocity, stroke volume, respiratory rate, and end-tidal gases were continuously measured. The Vanderbilt Orthostatic Symptom Score was compiled at the end of tilt. The use of the collar reduced the orthostatic symptom score of participants with POTS during upright tilt (26.9 ± 12.5 to 18.7 ± 13.1, P = 0.04). Collar compression in the supine condition reduced the low-frequency domain of HR variability (60 ± 18 to 51 ± 23 normalized units, P = 0.04) and increased the change in HR (15 ± 5 to 17 ± 6 bpm, P = 0.02) and E:I ratio (1.2 ± 0.1 to 1.3 ± 0.1, P = 0.01) during paced deep breathing. Throughout tilt, wearing the collar reduced respiratory rate (baseline: 13 ± 3 to 12 ± 4 breath/min; tilt: 18 ± 5 to 15 ± 5 breath/min; main effect of collar P = 0.048), end-tidal oxygen (baseline: 115 ± 5 to 112 ± 5 mmHg; tilt: 122 ± 10 to 118 ± 11 mmHg; main effect of collar P = 0.026). In participants with POTS, wearing the Q-collar reduced orthostatic symptoms, increased the HR response to deep breathing, and decreased resting ventilation.NEW & NOTEWORTHY We found that using a neck compression collar alleviated orthostatic symptoms in upright posture in participants with postural orthostatic tachycardia syndrome (POTS). This could be due to compression of the baroreceptors and subsequent changes in autonomic function. Indeed, we observed increased heart rate responsiveness to paced deep breathing and reductions of respiratory rate and end-tidal O2 (suggesting reduced ventilation). Further, wearing the collar reduced mean blood velocity in the brain during Valsalva perhaps due to higher brain blood volume.