Cerebrovascular adaptations to habitual resistance exercise with aging.

Resistance training (RT) is associated with improved metabolism, bone density, muscular strength, and lower risk of osteoporosis, sarcopenia, and cardiovascular disease. Although RT imparts many physiological benefits, cerebrovascular adaptations to chronic RT are not well defined. Participation in RT is associated with greater resting peripheral arterial diameters, improved endothelial function, and general cardiovascular health, whereas simultaneously linked to reductions in central arterial compliance. Rapid blood pressure fluctuations during resistance exercise, combined with reduced arterial compliance, could lead to cerebral microvasculature damage and subsequent cerebral hypoperfusion. Reductions in cerebral blood flow (CBF) accompany normal aging, where chronic reductions in CBF are associated with changes in brain structure and function, and increased risk of neurodegeneration. It remains unclear whether reductions in arterial compliance with RT relate to subclinical cerebrovascular pathology, or if such adaptations require interpretation in the context of RT specifically. The purpose of this narrative review is to synthesize literature pertaining to cerebrovascular adaptations to RT at different stages of the life span. This review also aims to identify gaps in the current understanding of the long-term impacts of RT on cerebral hemodynamics and provide a mechanistic rationale for these adaptations as they relate to aging, cerebral vasculature, and overall brain health.

Impact of ischemic heart disease and cardiac rehabilitation on cerebrovascular compliance.

We aimed to determine the influence of ischemic heart disease (IHD) and cardiac rehabilitation (CR) on cerebrovascular compliance index (Ci). Eleven (one female) patients with IHD (mean[SD]: 61[11] yr, 29[4] kg/m2) underwent 6 mo of CR, which consisted of ≥3 sessions/wk of aerobic and resistance training (20-60 min each). Ten (three female) similarly aged controls (CON) were tested at baseline as a comparator group. Middle cerebral artery velocity (MCAv) and mean arterial pressure were monitored continuously using transcranial Doppler ultrasound and finger photoplethysmography, respectively, during a rapid sit-to-stand maneuver. A Windkessel model was used to estimate cerebrovascular Ci every five cardiac cycles for a duration of 30 s. Cerebrovascular resistance was calculated as the quotient of MAP and MCAv. Two-way ANOVAs were used to determine whether cerebrovascular variables differ during postural transitions between groups and after CR. Baseline MCAv was higher in CON versus IHD (P = 0.014) and a time × group interaction was observed (P = 0.045) where MCAv decreased more in CON after standing. Compared with the precondition, CR had no effect on MCAv (condition P = 0.950) but a main effect of time indicated that MCAv decreased from the seated position in both conditions (time P = 0.013). Baseline cerebrovascular Ci was greater in IHD versus CON (P = 0.049) and the peak cerebrovascular Ci during the transition to standing was significantly higher in IHD compared with CON (interaction P = 0.047). CR did not affect cerebrovascular compliance (P = 0.452) and no time-by-condition interaction upon standing was present (P = 0.174). Baseline cerebrovascular Ci is higher in IHD at baseline compared with CON, but 6 mo of CR did not modify the transient increase in cerebrovascular Ci during sit-to-stand maneuvers.NEW & NOTEWORTHY Post-cardiac event cognitive impairment is common and exercise-based rehabilitation may be an effective intervention to mitigate cognitive decline. Microvascular damage due to high blood pressure pulsatility entering the brain is the putative mechanism of vascular dementia. Whether patients with ischemic heart disease exhibit lower cerebrovascular compliance, and if cardiac rehabilitation can improve cerebrovascular compliance is unknown. We observed that patients with ischemic heart disease have paradoxically higher cerebrovascular compliance, which is not affected by cardiac rehabilitation.

Association of Arterial Stiffness Index and Brain Structure in the UK Biobank: A 10-Year Retrospective Analysis.

Arterial stiffening and changes in brain structure both occur with normal aging and can be exacerbated via acquired health conditions. While cross-sectional associations exist, the longitudinal relationship between arterial stiffness and brain structure remains unclear. In this study, we investigated 1) associations between baseline arterial stiffness index (ASI) and brain structure (global and regional grey matter volumes (GMV), white matter hyperintensities (WMH)) 10-years post-baseline (10.4±0.8 years) and 2) associations between the 10-year change in ASI from baseline and brain structure 10-years post-baseline in 650 healthy middle- to older-aged adults (53.4±7.5 years) from the UK Biobank. We observed significant associations between baseline ASI and GMV (p<0.001) and WMH (p=0.0036) 10-years post-baseline. No significant associations between 10-year change in ASI and brain structure (global GMV p=0.24; WMH volume p=0.87) were observed. There were significant associations of baseline ASI in 2 of 60 regional brain volumes analyzed (right posterior superior temporal gyrus p=0.001; left superior lateral occipital cortex p<0.001). Strong associations with baseline ASI, but not changes in ASI over 10-years, suggest arterial stiffness at the entry point of older adulthood is more impactful on brain structure 10-years later compared to age-related stiffening. Based on these associations, we suggest clinical monitoring and potential intervention for reducing arterial stiffness should occur in midlife to reduce vascular contributions to structural changes in the brain, supporting a healthy trajectory of brain aging. Our findings also support use of ASI as a surrogate for gold standard measures in showing overall relationships between arterial stiffness and brain structure.

Hemodynamic Modeling, Medical Imaging, and Machine Learning and Their Applications to Cardiovascular Interventions.

Cardiovascular disease is a deadly global health crisis that carries a substantial financial burden. Innovative treatment and management of cardiovascular disease straddles medicine, personalized hemodynamic modeling, machine learning, and modern imaging to help improve patient outcomes and reduce the economic impact. Hemodynamic modeling offers a non-invasive method to provide clinicians with new pre- and post- procedural metrics and aid in the selection of treatment options. Medical imaging is an integral part in clinical workflows for understanding and managing cardiac disease and interventions. Coupling machine learning with modeling, and cardiovascular imaging, provides faster modeling, improved data fidelity, and an enhanced understanding and earlier detection of cardiovascular anomalies, leading to the development of patient-specific diagnostic and predictive tools for characterizing and assessing cardiovascular outcomes. Herein, we provide a scoping review of translational hemodynamic modeling, medical imaging, and machine learning and their applications to cardiovascular interventions. We particularly focus on providing an intuitive understanding of each of these approaches and their ability to support decision making during important clinical milestones.

Roles of Hormone Replacement Therapy and Menopause on Osteoarthritis and Cardiovascular Disease Outcomes: A Narrative Review.

Osteoarthritis (OA) is a highly prevalent condition characterized by degradation of the joints. OA and cardiovascular disease (CVD) are leading contributors to disease burden worldwide, with a high level of overlap between the risk factors and occurrence of both conditions. Chief among the risk factors that contribute to OA and CVD are sex and age, which are both independent and interacting traits. Specifically, the prevalence of both conditions is higher in older women, which may be mediated by the occurrence of menopause. Menopause represents a significant transition in a women's life, and the rapid decline in circulating sex hormones, estrogen and progesterone, leads to complex physiological changes. Declines in hormone levels may partially explain the increase in prevalence of OA and CVD in post-menopausal women. In theory, the use of hormone therapy (HT) may buffer adverse effects of menopause; however, it is unclear whether HT offers protective effects for the onset or progression of these diseases. Studies have shown mixed results when describing the influence of HT on disease risk among post-menopausal women, which warrants further exploration. The roles that increasing age, female sex, HT, and CVD play in OA risk demonstrate that OA is a multifaceted condition. This review provides a timely consolidation of current literature and suggests aims for future research directions to bridge gaps in the understanding of how OA, CVD, and HT interact in post-menopausal women.

Cerebral haemodynamics during arrhythmia in health, ischaemic heart disease and heart failure with reduced ejection fraction, and in a preclinical swine model.

Ventricular arrhythmias are associated with neurological impairment and could represent a source of cerebral hypoperfusion. In the present study, data from healthy individuals (n = 11), patients with ischaemic heart disease (IHD; ejection fraction >40%; n = 9) and patients with heart failure with reduced ejection fraction (HFrEF; EF = 31 (5)%, n = 11), as well as data from swine surgeries, where spontaneous ventricular arrhythmias were observed during cerebrovascular examination (transcranial Doppler ultrasound in humans and laser Doppler in swine) were analysed retrospectively to investigate the effect of arrhythmia on cerebral microvascular haemodynamics. A subset of participants also completed the Montreal Cognitive Assessment (MoCA). Middle cerebral artery mean blood velocity (MCAVmean ) decreased during premature ventricular contraction (PVC) in all groups, and data from swine indicate PVCs reduced cerebral microvascular perfusion. Overall MCAVmean was decreased in the HFrEF vs. control group. Further, %∆MCAVmean /%∆mean arterial pressure during the PVC was greater in the HFrEF vs. control group and was correlated with decreased MoCA scores. Subanalysis of HFrEF data revealed that during bigeminy MCAVmean decreased owing to reductions during irregular beats only. During non-sustained ventricular tachycardia, MCAVmean decreased but recovered above baseline upon return to sinus rhythm. Also, haemodynamic perturbations during and following the PVC were greater in the brachial artery vs. the MCA. Therefore, ventricular arrhythmias decreased indices of cerebral perfusion irrespective of IHD or HFrEF. The relative magnitude of arrhythmia-induced haemodynamic perturbations appears to be population specific and arrhythmia type and organ dependent. The cumulative burden of arrhythmia-induced deficits may exacerbate existing cerebral hypoperfusion in HFrEF and contribute to neurological abnormalities in this population. KEY POINTS: Irregular heartbeats are often considered benign in isolation, but individuals who experience them frequently have a higher prevalence of cerebrovascular and/or cognitive associated disorders. How irregular heartbeats affect blood pressure and cerebral haemodynamics in healthy and cardiovascular disease patients, those with and without reduced ejection fraction, remains unknown. Here it was found that in the absence of symptoms associated with irregular heartbeats, such as dizziness or hypotension, single, multiple non-sustained and sustained irregular heartbeats influence cerebral haemodynamics in a population-specific, arrhythmia-type and organ-dependent manner. Relative deficits in the index of cerebral blood flow normalized to relative deficits in blood pressure were greatest in patients with heart failure with reduced ejection and inversely related with cognitive performance. Chronic arrhythmias may exacerbate existing cerebral hypoperfusion in heart failure with reduced ejection fraction, thereby providing a mechanistic link between otherwise benign irregular heartbeats and cognitive dysfunction, independent of embolism.

What are the effects of acute exercise and exercise training on cerebrovascular hemodynamics following stroke? A systematic review and meta-analysis.

Limited data exist regarding the effects of acute exercise and exercise training on cerebrovascular hemodynamic variables after stroke. This systematic review and meta-analysis 1) examined the effects of acute exercise and exercise training on cerebrovascular hemodynamic variables reported in the stroke exercise literature and 2) synthesized the peak middle cerebral artery blood velocity (MCAv) achieved during an acute bout of moderate-intensity exercise in individuals after stroke. Six databases (Medline, Embase, Web of Science, CINAHL, PsycINFO, AMED) were searched from inception to December 1st, 2021 for studies that examined the effect of acute exercise or exercise training on cerebrovascular hemodynamics in adults after stroke. Two reviewers conducted title and abstract screening, full-text evaluation, data extraction, and quality appraisal. Random-effects models were used in meta-analysis. Nine studies, including four acute exercise (n = 61) and five exercise training studies (n = 193), were included. Meta-analyses were not statistically feasible for several cerebrovascular hemodynamic variables. Descriptive analysis reveals that exercise training may increase cerebral blood flow and cerebrovascular reactivity to carbon dioxide among individuals after stroke. Meta-analysis of three acute exercise studies revealed no significant changes in MCAv during acute moderate-intensity exercise [n = 48 participants, mean difference = 5.2 cm/s, 95% confidence interval (CI) [-0.6, 11.0], P = 0.08] compared with resting MCAv values. This review suggests that individuals after stroke may have attenuated cerebrovascular hemodynamics as measured by the MCAv during acute moderate-intensity exercise. Aerobic exercise training is beneficial for improving cardiovascular health and function after stroke; higher-quality research utilizing agreed-upon hemodynamic variables is needed to synthesize the effects of exercise training on poststroke cerebrovascular hemodynamics.

Expression of hypoxia inducible factor-dependent neuropeptide Y receptors Y1 and Y5 sensitizes hypoxic cells to NPY stimulation.

Neuropeptide Y (NPY) is an abundant neurohormone in the central and peripheral nervous system involved in feeding behavior, energy balance, nociception, and anxiety. Several NPY receptor (NPYR) subtypes display elevated expression in many cancers including in breast tumors where it is exploited for imaging and diagnosis. Here, we address how hypoxia, a common feature of the tumor microenvironment, influences the expression of the NPYRs. We show that NPY1R and NPY5R mRNA abundance is induced by hypoxia in a hypoxia inducible factor (HIF)-dependent manner in breast cancer cell lines MCF7 and MDA-MB-231. We demonstrate that HIFs bind to several genomic regions upstream of the NPY1R and NPY5R transcription start sites. In addition, the MAPK/ERK pathway is activated more rapidly upon NPY5R stimulation in hypoxic cells compared with normoxic cells. This pathway requires insulin-like growth factor 1 receptor (IGF1R) activity in normoxia, but not in hypoxic cells, which display resistance to the radiosensitizer and IGF1R inhibitor AG1024. Furthermore, hypoxic cells proliferate and migrate more when stimulated with NPY relative to normoxic cells and exhibit a more robust response to a Y5-specific agonist. Our data suggest that hypoxia-induced NPYRs render hypoxic cells more sensitive to NPY stimulation. Considering that breast tissue receives a constant supply of NPY, hypoxic breast tumors are the perfect storm for hyperactive NPYR. This study not only highlights a new relationship between the HIFs and NPYR expression and activity but may inform the use of chemotherapeutics targeting NPYRs and hypoxic cells.

Protocol-dependence of middle cerebral artery dilation to modest hypercapnia.

There is a need for improved understanding of how different cerebrovascular reactivity (CVR) protocols affect vascular cross-sectional area (CSA) to reduce error in CVR calculations when measures of vascular CSA are not feasible. In human participants, we delivered ∼±4 mm Hg end-tidal partial pressure of CO2 (PETCO2) relative to baseline through controlled delivery, and measured changes in middle cerebral artery (MCA) CSA (7 Tesla magnetic resonance imaging (MRI)), blood velocity (transcranial Doppler and Phase contrast MRI), and calculated CVR based on a 3-minute steady-state (+4 mm Hg PETCO2) and a ramp (-3 to +4 mm Hg of PETCO2). We observed that (1) the MCA did not dilate during the ramp protocol (slope for CSA across time P > 0.05; R2 = 0.006), but did dilate by ∼7% during steady-state hypercapnia (P < 0.05); and (2) MCA blood velocity CVR was not different between ramp and steady-state hypercapnia protocols (ramp: 3.8 ± 1.7 vs. steady-state: 4.0 ± 1.6 cm/s/mm Hg), although calculated MCA blood flow CVR was ∼40% greater during steady-state hypercapnia than during ramp (P < 0.05) with the discrepancy due to MCA CSA changes during steady-state hypercapnia. We propose that a ramp model, across a delta of -3 to +4 mm Hg PETCO2, may provide an alternative approach to collecting CVR measures in young adults with transcranial Doppler when CSA measures are not feasible. Novelty: We optimized a magnetic resonance imaging sequence to measure dynamic middle cerebral artery (MCA) cross-sectional area (CSA). A ramp model of hypercapnia elicited similar MCA blood velocity reactivity as the steady-state model while maintaining MCA CSA.

Exercise-induced bronchoconstriction and bronchodilation: investigating the effects of age, sex, airflow limitation and FEV1.

Exercise-induced bronchoconstriction (EIBc) is a recognised response to exercise in asthmatic subjects and athletes but is less well understood in an unselected broad population. Exercise-induced bronchodilation (EIBd) has received even less attention. The objective of this study was to investigate the effects of age, sex, forced expiratory volume in 1 s (FEV1) and airflow limitation (FEV1/forced vital capacity (FVC) <0.7) on the prevalence of EIBc and EIBd.This was a retrospective study based on incremental cardiopulmonary exercise testing on cycle ergometry to symptom limitation performed between 1988 and 2012. FEV1 was measured before and 10 min after exercise. EIBc was defined as a percentage fall in FEV1 post-exercise below the 5th percentile, while EIBd was defined as a percentage increase in FEV1 above the 95th percentile.35 258 subjects aged 6-95 years were included in the study (mean age 53 years, 60% male) and 10.3% had airflow limitation (FEV1/FVC <0.7). The lowest 5% of subjects demonstrated a ≥7.6% fall in FEV1 post-exercise (EIBc), while the highest 5% demonstrated a >11% increase in FEV1 post-exercise (EIBd). The probability of both EIBc and EIBd increased with age and was highest in females across all ages (OR 1.76, 95% CI 1.60-1.94; p<0.0001). The probability of EIBc increased as FEV1 % pred declined (<40%: OR 4.38, 95% CI 3.04-6.31; p<0.0001), with a >2-fold increased likelihood in females (OR 2.31, 95% CI 1.71-3.11; p<0.0001), with a trend with airflow limitation (p=0.06). The probability of EIBd increased as FEV1 % pred declined, in the presence of airflow limitation (OR 1.55, 95% CI 1.24-1.95; p=0.0001), but sex had no effect.EIBc and EIBd can be demonstrated at the population level, and are influenced by age, sex, FEV1 % pred and airflow limitation.

The impact of the 24-h movement spectrum on vascular remodeling in older men and women: a review.

Aging is associated with increased risk of cardiovascular and cerebrovascular events, which are preceded by early, negative remodeling of the vasculature. Low physical activity is a well-established risk factor associated with the incidence and development of disease. However, recent physical activity literature indicates the importance of considering the 24-h movement spectrum. Therefore, the purpose of this review was to examine the impact of the 24-h movement spectrum, specifically physical activity (aerobic and resistance training), sedentary behavior, and sleep, on cardiovascular and cerebrovascular outcomes in older adults, with a focus on recent evidence (<10 yr) and sex-based considerations. The review identifies that both aerobic training and being physically active (compared with sedentary) are associated with improvements in endothelial function, arterial stiffness, and cerebrovascular function. Additionally, there is evidence of sex-based differences in endothelial function: a blunted improvement in aerobic training in postmenopausal women compared with men. While minimal research has been conducted in older adults, resistance training does not appear to influence arterial stiffness. Poor sleep quantity or quality are associated with both impaired endothelial function and increased arterial stiffness. Finally, the review highlights mechanistic pathways involved in the regulation of vascular and cerebrovascular function, specifically the balance between pro- and antiatherogenic factors, which mediate the relationship between the 24-h movement spectrum and vascular outcomes. Finally, this review proposes future research directions: examining the role of duration and intensity of training, combining aerobic and resistance training, and exploration of sex-based differences in cardiovascular and cerebrovascular outcomes.

Does vascular stiffness predict white matter hyperintensity burden in ischemic heart disease with preserved ejection fraction?

The survival rate of patients with ischemic heart disease (IHD) is increasing. However, survivors experience increased risk for neurological complications. The mechanisms for this increased risk are unknown. We tested the hypothesis that patients with IHD have greater carotid and cerebrovascular stiffness, and these indexes predict white matter small vessel disease. Fifty participants (age, 40-78 yr), 30 with IHD with preserved ejection fraction and 20 healthy age-matched controls, were studied using ultrasound imaging of the common carotid artery (CCA) and middle cerebral artery (MCA), as well as magnetic resonance imaging (T1, T2-FLAIR), to measure white matter lesion volume (WMLv). Carotid ß-stiffness provided the primary measure of peripheral vascular stiffness. Carotid-cerebral pulse wave transit time (ccPWTT) provided a marker of cerebrovascular stiffness. Pulsatility index (PI) and resistive index (RI) of the MCA were calculated as measures of downstream cerebrovascular resistance. When compared with controls, patients with IHD exhibited greater ß-stiffness [8.5 ± 3.3 vs. 6.8 ± 2.2 arbitrary units (AU); P = 0.04], MCA PI (1.1 ± 0.20 vs. 0.98 ± 0.18 AU; P = 0.02), and MCA RI (0.66 ± 0.06 vs. 0.62 ± 0.07 AU; P = 0.04). There was no difference in WMLv between IHD and control groups (0.95 ± 1.2 vs. 0.86 ± 1.4 mL; P = 0.81). In pooled patient data, WMLv correlated with both ß-stiffness (R = 0.34, P = 0.02) and cerebrovascular ccPWTT (R = -0.43, P = 0.02); however, ß-stiffness and ccPWTT were not associated (P = 0.13). In multivariate analysis, WMLv remained independently associated with ccPWTT (P = 0.02) and carotid ß-stiffness (P = 0.04). Patients with IHD expressed greater ß-stiffness and cerebral microvascular resistance. However, IHD did not increase risk of WMLv or cerebrovascular stiffness. Nonetheless, pooled data indicate that both carotid and cerebrovascular stiffness are independently associated with WMLv.NEW & NOTEWORTHY This study found that patients with ischemic heart disease (IHD) with preserved ejection fraction and normal blood pressures exhibit greater carotid ß-stiffness, as well as middle cerebral artery pulsatility and resistive indexes, than controls. White matter lesion volume (WMLv) was not different between vascular pathology groups. Cerebrovascular pulse wave transit time (ccPWTT) and carotid ß-stiffness independently associate with WMLv in pooled participant data, suggesting that regardless of heart disease history, ccPWTT and ß-stiffness are associated with structural white matter damage.

Are we missing the target? Are we aiming too low? What are the aerobic exercise prescriptions and their effects on markers of cardiovascular health and systemic inflammation in patients with knee osteoarthritis? A systematic review and meta-analysis.

OBJECTIVES: We systemically reviewed published studies that evaluated aerobic exercise interventions in patients with knee osteoarthritis (OA) to: (1) report the frequency, intensity, type and time (FITT) of exercise prescriptions and (2) quantify the changes in markers of cardiovascular health and systemic inflammation. DATA SOURCES: PubMed, CINAHL, Scopus; inception to January 2019. ELIGIBILITY CRITERIA: Randomised clinical trials (RCT), cohort studies, case series. DESIGN: We summarised exercise prescriptions for all studies and calculated effect sizes with 95% CIs for between-group (RCTs that compared exercise and control groups) and within-group (pre-post exercise) differences in aerobic capacity (VO2), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and inflammatory markers (interleukin-6 (IL-6), tumour necrosis factor-alpha). We pooled results where possible using random effects models. RESULTS: Interventions from 49 studies were summarised; 8% (4/49) met all FITT guidelines; 16% (8/49) met all or most FITT guidelines. Fourteen studies (10 RCTs) reported at least one marker of cardiovascular health or systemic inflammation. Mean differences (95% CI) indicated a small to moderate increase in VO2 (0.84 mL/min/kg; 95% CI 0.37 to 1.31), decrease in HR (-3.56 beats per minute; 95% CI -5.60 to -1.52) and DBP (-4.10 mm Hg; 95% CI -4.82 to -3.38) and no change in SBP (-0.36 mm Hg; 95% CI -3.88 to 3.16) and IL-6 (0.37 pg/mL; 95% CI -0.11 to 0.85). Within-group differences were also small to moderate. CONCLUSIONS: In studies of aerobic exercise in patients with knee OA, very few interventions met guideline-recommended dose; there were small to moderate changes in markers of cardiovascular health and no decrease in markers of systemic inflammation. These findings question whether aerobic exercise is being used to its full potential in patients with knee OA. PROSPERO REGISTRATION NUMBER: CRD42018087859.

Exploring Cerebrovascular Function in Osteoarthritis: "Heads-up".

Individuals with osteoarthritis (OA) are at greater risk of cardiovascular and cerebrovascular incidents; yet, cerebrovascular control remains uncharacterized. Our primary outcome was to acquire cerebrovascular control metrics in patients with OA and compare measures to healthy control adults (CTL) without OA or cardiovascular complications. Our primary covariate was a 10-year risk factor for cardiovascular and stroke incidents, and secondary covariates were other cardiovascular disease risk factors (i.e., body mass index, carotid intima media thickness, and brachial flow-mediated dilation). Our secondary outcomes were to assess anatomical and functional changes that may be related to cerebrovascular reactivity were also acquired such as white matter lesion volume and brief cognitive assessments. In 25 adults (n = 13 CTL, n = 12 OA), under hypercapnia, magnetic resonance imaging (3T) was used to acquire a "Global Cerebrovascular Reactivity" index across the larger intracranial cerebral arteries and white matter lesions, and transcranial Doppler was used for both middle cerebral artery hemodynamic responses to hypercapnia and to assess autoregulation via a sit-to-stand task. Compared to CTL, OA had lower "Global Cerebrovascular Reactivity" index responses to hypercapnia, autoregulatory responses, and greater white matter lesions (P < 0.05). These differences persisted after covarying for the outlined primary and secondary covariates. Patients with OA, in the absence of known cardiovascular disease, can exhibit pre-clinical and impaired (compared to CTL) peripheral and cerebrovascular control metrics.

Impaired dynamic cerebral autoregulation in trained breath-hold divers.

Breath-hold divers (BHD) experience repeated bouts of severe hypoxia and hypercapnia with large increases in blood pressure. However, the impact of long-term breath-hold diving on cerebrovascular control remains poorly understood. The ability of cerebral blood vessels to respond rapidly to changes in blood pressure represents the property of dynamic autoregulation. The current investigation tested the hypothesis that breath-hold diving impairs dynamic autoregulation to a transient hypotensive stimulus. Seventeen BHD (3 women, 11 ± 9 yr of diving) and 15 healthy controls (2 women) completed two or three repeated sit-to-stand trials during spontaneous breathing and poikilocapnic conditions. Heart rate (HR), finger arterial blood pressure (BP), and cerebral blood flow velocity (BFV) from the right middle cerebral artery were measured continuously with three-lead electrocardiography, finger photoplethysmography, and transcranial Doppler ultrasonography, respectively. End-tidal carbon dioxide partial pressure was measured with a gas analyzer. Offline, an index of cerebrovascular resistance (CVRi) was calculated as the quotient of mean BP and BFV. The rate of the drop in CVRi relative to the change in BP provided the rate of regulation [RoR; (∆CVRi/∆T)/∆BP]. The BHD demonstrated slower RoR than controls (P ≤ 0.001, d = 1.4). Underlying the reduced RoR in BHD was a longer time to reach nadir CVRi compared with controls (P = 0.004, d = 1.1). In concert with the longer CVRi response, the time to reach peak BFV following standing was longer in BHD than controls (P = 0.01, d = 0.9). The data suggest impaired dynamic autoregulatory mechanisms to hypotension in BHD. NEW & NOTEWORTHY Impairments in dynamic cerebral autoregulation to hypotension are associated with breath-hold diving. Although weakened autoregulation was observed acutely in this group during apneic stress, we are the first to report on chronic adaptations in cerebral autoregulation. Impaired vasomotor responses underlie the reduced rate of regulation, wherein breath-hold divers demonstrate a prolonged dilatory response to transient hypotension. The slower cerebral vasodilation produces a longer perturbation in cerebral blood flow velocity, increasing the risk of cerebral ischemia.

Increased blood pressure is associated with increased carotid artery intima-media thickness in children with repaired coarctation of the aorta.

OBJECTIVES: The intima-media thickness of the common carotid artery (cIMT) is a good noninvasive surrogate marker for cardiovascular disease. Regular cIMT monitoring in children with congenital heart disease has great potential. We sought to determine which anthropomorphic and haemodynamic variables were significantly associated with the cIMT in paediatric patients with obesity and children with repaired coarctation of the aorta (CoA). METHODS: We measured the cIMT in 143 children aged 5 to less than 18 years including normal weight controls (n = 44), children with overweight/obesity (n = 73) and children with repaired CoA (n = 26). cIMT was compared and the association between the cIMT and patient characteristics, including obesity and blood pressure (BP), was investigated. RESULTS: BMI z score, sex and the presence of CoA were significant independent predictors of cIMT. The cIMT was significantly greater in children with overweight/obesity (0.53 ±â€Š0.06 mm) relative to normal weight controls (0.51 ±â€Š0.04 mm), as well as in CoA patients with abnormally high BP (0.57 ±â€Š0.08 mm) versus CoA patients with normal BP (0.52 ±â€Š0.05 mm) and controls (0.51 ±â€Š0.04 mm). CoA patients with normal BP did not have significantly increased cIMT. CONCLUSION: cIMT was positively associated with BMI z score, male sex and CoA repair in children. The increased cIMT in children with repaired CoA was because of those with abnormally high BP, which was masked in clinic for most of these patients. These findings warrant further investigations into the cIMT and other atherosclerotic risk factors to determine their potential clinical impact in these highly susceptible patients.

Reactivity of larger intracranial arteries using 7 T MRI in young adults.

The larger intracranial conduit vessels contribute to the total cerebral vascular resistance, and understanding their vasoreactivity to physiological stimuli is required when attempting to understand regional brain perfusion. Reactivity of the larger cerebral conduit arteries remains understudied due to a need for improved imaging methods to simultaneously assess these vessels in a single stimulus. We characterized reactivity of basal intracranial conduit arteries (basilar, right and left posterior, middle and anterior cerebral arteries) and the right and left internal carotid arteries, to manipulations in end-tidal CO2 (PetCO2). Cross-sectional area changes (%CSA) were evaluated from high-resolution (0.5 mm isotropic) images collected at 7 T using a T1-weighted 3D SPACE pulse sequence, providing high contrast between vessel lumen and surrounding tissue. Cerebrovascular reactivity was calculated as %CSA/ΔPetCO2 in eight healthy individuals (18-23 years) during normocapnia (41 ± 4 mmHg), hypercapnia (48 ± 4 mmHg; breathing 5% CO2, balance oxygen), and hypocapnia (31 ± 8 mmHg; via hyperventilation). Reactivity to hypercapnia ranged from 0.8%/mmHg in the right internal carotid artery to 2.7%/mmHg in the left anterior cerebral artery. During hypocapnia, vasoconstriction ranged from 0.9%/mmHg in the basilar artery to 2.6%/mmHg in the right posterior cerebral artery. Heterogeneous cerebrovascular reactivity to hypercapnia and hypocapnia was characterized across basal intracranial conduit and internal carotid arteries.

The human cortical autonomic network and volitional exercise in health and disease.

The autonomic nervous system elicits continuous beat-by-beat homeostatic adjustments to cardiovascular control. These modifications are mediated by sensory inputs (e.g., baroreceptors, metaboreceptors, pulmonary, thermoreceptors, and chemoreceptors afferents), integration at the brainstem control centres (i.e., medulla), and efferent autonomic neural outputs (e.g., spinal, preganglionic, and postganglionic pathways). However, extensive electrical stimulation and functional imaging research show that the brain's higher cortical regions (e.g., insular cortex, medial prefrontal cortex, anterior cingulate cortex) partake in homeostatic regulation of the cardiovascular system at rest and during exercise. We now appreciate that these cortical areas form a network, namely the "cortical autonomic network" (CAN), which operate as part of a larger central autonomic network comprising 2-way communication of cortical and subcortical areas to exert autonomic influence. Interestingly, differential patterns of CAN activity and ensuing cardiovascular control are present in disease states, thereby highlighting the importance of considering the role of CAN as an integral aspect of cardiovascular regulation in health and disease. This review discusses current knowledge on human cortical autonomic activation during volitional exercise, and the role of exercise training on this activation in both health and disease.

Sodium nitroglycerin induces middle cerebral artery vasodilatation in young, healthy adults.

NEW FINDINGS: What is the central question of this study? Nitric oxide causes dilatation in peripheral vessels; however, whether nitric oxide affects basal cerebral artery dilatation has not been explored. What is the main finding and its importance? This study demonstrated that vasodilatation occurs in the right middle cerebral artery in response to exogenous nitric oxide. However, blood velocity decreased and, therefore, overall cerebral blood flow remained unchanged. This study provides new insight into the role of nitric oxide in cerebral blood flow control. ABSTRACT: Recent evidence indicates that basal cerebral conduit vessels dilate with hypercapnia, with a nitric oxide (NO) mechanism explaining one way in which parenchymal cerebral arterioles dilate. However, whether NO affects basal cerebral artery dilatation remains unknown. This study quantified the effect of an exogenous NO donor [sodium nitroglycerin (NTG); 0.4 mg sublingual spray] on the right middle cerebral artery (rMCA) cross-sectional area (CSA), blood velocity and overall blood flow. Measures of vessel CSA (7 T magnetic resonance imaging) and MCA blood velocity (transcranial Doppler ultrasound) were made at baseline (BL) and after exogenous NTG or placebo (PLO) administration in young, healthy individuals (n = 10, two males, age range 20-23 years). The CSA increased in the rMCA [BL, 5.2 ± 1.2 mm2 ; PLO, 5.4 ± 1.5 mm2 ; NTG, 6.6 ± 1.5 mm2 , P < 0.05; mean ± SD]. Concurrently, rMCA blood velocity decreased from BL during NTG compared with PLO (BL, 67 ± 10 cm s-1 ; PLO, 62 ± 10 cm s-1 ; NTG, 59 ± 9.3 cm s-1 , P < 0.05; mean ± SD]. However, total MCA blood flow did not change with NTG or PLO [BL, 221 ± 37.4 ml min-1 ; PLO, 218 ± 35.0 ml min-1 ; NTG, 213 ± 46.4 ml min-1 ). Therefore, exogenous NO mediates a dilatory response in the rMCA, but not in its downstream vascular bed.