Short-term vascular responses to spring and fall daylight savings time shifts.

Daylight saving time (DST) is a Western biannual time transition, setting the clock back 1 h in the fall and forward 1 h in the spring. There is an epidemiological link between DST and acute myocardial infarction risk in the first week following the spring shift; however, the mechanisms underlying the effect of DST on cardiovascular function remain unclear. The purpose of this study was to explore the short-term cardiovascular changes induced by fall and spring shifts in DST in a convenience sample of healthy adults. We hypothesized that spring, but not fall, DST shifts would acutely increase central pulse wave velocity, the gold standard measurement of central arterial stiffness. Twenty-one individuals (fall: n = 10; spring: n = 11) participated in four visits, occurring 1 wk before and at +1, +3, and +5 days after spring and fall time transitions. Central, brachial, and radial pulse wave velocity as well as carotid augmentation index were assessed with applanation tonometry. Sleep quality and memory function were assessed via questionnaire and the Mnemonic Similarities Task, respectively. Neither fall or spring transition resulted in changes to cardiovascular variables (carotid-femoral pulse wave velocity, carotid-brachial pulse wave velocity, carotid-radial pulse wave velocity, heart rate, mean arterial pressure, or augmentation index), sleep quality, or cognitive function (all P > 0.05). Our findings do not provide evidence that DST shifts influence cardiovascular outcomes in healthy adults. This study emphasizes the need for further research to determine the mechanisms of increased cardiovascular disease risk with DST that help explain epidemiological trends.NEW & NOTEWORTHY The debate of whether to abolish daylight savings time (DST) is, in part, motivated by the population-level increase in all-cause mortality and incidence of cardiovascular events following DST; however, there is an absence of data to support a physiological basis for risk. We found no changes in pulse wave velocity or augmentation index during the subacute window of DST. Large multisite trials are necessary to address the small, but meaningful, effects brought on by a societal event.

Attenuating intrathoracic pressure swings decreases cardiac output at different intensities of exercise.

Intrathoracic pressure (ITP) swings that permit spontaneous ventilation have physiological implications for the heart. We sought to determine the effect of respiration on cardiac output ( Q ̇ $\dot Q$ ) during semi-supine cycle exercise using a proportional assist ventilator to minimize ITP changes and lower the work of breathing (Wb ). Twenty-four participants (12 females) completed three exercise trials at 30%, 60% and 80% peak power (Wmax ) with unloaded (using a proportional assist ventilator, PAV) and spontaneous breathing. Intrathoracic and intraabdominal pressures were measured with balloon catheters placed in the oesophagus and stomach. Left ventricular (LV) volumes and Q ̇ $\dot Q$ were determined via echocardiography. Heart rate (HR) was measured with electrocardiogram and a customized metabolic cart measured oxygen uptake ( V ̇ O 2 ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}}}$ ). Oesophageal pressure swings decreased from spontaneous to PAV breathing by -2.8 ± 3.1, -4.9 ± 5.7 and -8.1 ± 7.7 cmH2 O at 30%, 60% and 80% Wmax , respectively (P = 0.01). However, the decreases in Wb were similar across exercise intensities (27 ± 42 vs. 35 ± 24 vs. 41 ± 22%, respectively, P = 0.156). During PAV breathing compared to spontaneous breathing, Q ̇ $\dot Q$ decreased by -1.0 ± 1.3 vs. -1.4 ± 1.4 vs. -1.5 ± 1.9 l min-1 (all P < 0.05) and stroke volume decreased during PAV breathing by -11 ± 12 vs. -9 ± 10 vs. -7 ± 11 ml from spontaneous breathing at 30%, 60% and 80% Wmax , respectively (all P < 0.05). HR was lower during PAV breathing by -5 ± 4 beats min-1 at 80% Wmax (P < 0.0001). Oxygen uptake decreased by 100 ml min-1 during PAV breathing compared to spontaneous breathing at 80% Wmax (P < 0.0001). Overall, attenuating ITPs mitigated LV preload and ejection, thereby suggesting that the ITPs associated with spontaneous respiration impact cardiac function during exercise. KEY POINTS: Pulmonary ventilation is accomplished by alterations in intrathoracic pressure (ITP), which have physiological implications on the heart and dynamically influence the loading parameters of the heart. Proportional assist ventilation was used to attenuate ITP changes and decrease the work of breathing during exercise to examine its effects on left ventricular (LV) function. Proportional assist ventilation with progressive exercise intensities (30%, 60% and 80% Wmax ) led to reductions in cardiac output at all intensities, primarily through reductions in stroke volume. Decreases in LV end-diastolic volume (30% and 60% Wmax ) and increases in LV end-systolic volume (80% Wmax ) were responsible for the reduction in stroke volume. The relationship between cardiac output and oxygen uptake is disrupted during respiratory muscle unloading.

Serum concentrations of ketones increase after hand-ergometer exercise in persons with cervical spinal cord injuries: a preliminary prospective study.

STUDY DESIGN: Experimental study. OBJECTIVES: To compare lipid profiles during moderate-intensity exercise between persons with cervical spinal cord injuries (SCIC) and able-bodied controls (AB). SETTING: Wakayama Medical University, Japan. METHODS: Six participants with SCIC and six AB performed 30-min arm-crank exercise at 50% VO2peak. Blood samples were collected before (PRE), immediately (POST), and 60 min after exercise (REC). Concentrations of serum free fatty acids ([FFA]s), total ketone bodies ([tKB]s), acetoacetic acid ([AcAc]s), insulin ([Ins]s), and plasma catecholamines and glucose ([Glc]p) were assessed. RESULTS: Catecholamine concentrations in SCIC were lower than AB throughout the experiment (P < 0.001) and remained unchanged, while increased at POST in AB (P < 0.01). [FFA]s remained unchanged in both groups with no differences between groups. [tKB]s in SCIC tended to increase at REC from PRE (P = 0.043), while remaining unchanged in AB (P > 0.42). [AcAc]s in SCIC increased at REC from PRE and POST (P < 0.01) while remaining unchanged in AB (interactions of Group × Time P = 0.014). [Glc]p and [Ins]s were comparable between the groups throughout the study. CONCLUSION: Serum ketone bodies in SCIC increased after exercise while remaining unchanged in AB, suggesting that suppressed uptakes of serum ketone bodies from blood to the muscles in SCIC would partially contribute the increased serum ketones.

Physiological basis for longitudinal motion of the arterial wall.

As opposed to arterial distension in the radial plane, longitudinal wall motion (LWM) is a multiphasic and bidirectional displacement of the arterial wall in the anterograde (i.e., in the direction of blood flow) and retrograde (i.e., opposing direction of blood flow) directions. Although initially disregarded as imaging artifact, LWM has been consistently reported in ultrasound investigations in the past decade and is reproducible beat-to-beat, albeit with large interindividual variability across healthy and diseased populations. Emerging literature has sought to examine the mechanistic control of LWM to explain the shape and variability of the motion pattern but lacks considerations for key foundational vascular principles at the level of the arterial wall ultrastructure. The purpose of this review is to summarize the potential factors that underpin the causes and control of arterial LWM, spanning considerations from the arterial extracellular matrix to systems-level integrative theories. First, an overview of LWM and relevant aspects wall composition will be discussed, including major features of the multiphasic pattern, arterial wall extracellular components, tunica fiber orientations, and arterial longitudinal prestretch. Second, current theories on the systems-level physiological mechanisms driving LWM will be discussed in the context of available evidence including experimental human research, porcine studies, and mathematical models. Throughout, we discuss implications of these observations with suggestions for future priority research areas.

Construct validation of the leisure time physical activity questionnaire for people with SCI (LTPAQ-SCI).

STUDY DESIGN: Cross-sectional construct validation study. OBJECTIVES: To test the construct validity of the Leisure Time Physical Activity Questionnaire for People with Spinal Cord Injury (LTPAQ-SCI) by examining associations between the scale responses and cardiorespiratory fitness (CRF) in a sample of adults living with spinal cord injury (SCI). SETTING: Three university-based laboratories in Canada. METHODS: Participants were 39 adults (74% male; M age: 42 ± 11 years) with SCI who completed the LTPAQ-SCI and a graded exercise test to volitional exhaustion using an arm-crank ergometer. One-tailed Pearson's correlation coefficients were computed to examine the association between the LTPAQ-SCI measures of mild-, moderate-, heavy-intensity and total minutes per week of LTPA and CRF (peak volume of oxygen consumption [V̇O2peak] and peak power output [POpeak]). RESULTS: Minutes per week of mild-, moderate- and heavy-intensity LTPA and total LTPA were all positively correlated with V̇O2peak. The correlation between minutes per week of mild intensity LTPA and V̇O2peak was small-medium (r = 0.231, p = 0.079) while all other correlations were medium-large (rs ranged from 0.276 to 0.443, ps < 0.05). Correlations between the LTPAQ-SCI variables and POpeak were also positive but small (rs ranged from 0.087 to 0.193, ps > 0.05), except for a medium-sized correlation between heavy-intensity LTPA and POpeak (r = 0.294, p = 0.035). CONCLUSIONS: People with SCI who report higher levels of LTPA on the LTPAQ-SCI also demonstrate greater levels of CRF, with stronger associations between moderate- and heavy-intensity LTPA and CRF than between mild-intensity LTPA and CRF. These results provide further support for the construct validity of the LTPAQ-SCI as a measure of LTPA among people with SCI.

16p11.2 transcription factor MAZ is a dosage-sensitive regulator of genitourinary development.

Genitourinary (GU) birth defects are among the most common yet least studied congenital malformations. Congenital anomalies of the kidney and urinary tract (CAKUTs) have high morbidity and mortality rates and account for ∼30% of structural birth defects. Copy number variation (CNV) mapping revealed that 16p11.2 is a hotspot for GU development. The only gene covered collectively by all of the mapped GU-patient CNVs was MYC-associated zinc finger transcription factor (MAZ), and MAZ CNV frequency is enriched in nonsyndromic GU-abnormal patients. Knockdown of MAZ in HEK293 cells results in differential expression of several WNT morphogens required for normal GU development, including Wnt11 and Wnt4. MAZ knockdown also prevents efficient transition into S phase, affects transcription of cell-cycle regulators, and abrogates growth of human embryonic kidney cells. Murine Maz is ubiquitously expressed, and a CRISPR-Cas9 mouse model of Maz deletion results in perinatal lethality with survival rates dependent on Maz copy number. Homozygous loss of Maz results in high penetrance of CAKUTs, and Maz is haploinsufficient for normal bladder development. MAZ, once thought to be a simple housekeeping gene, encodes a dosage-sensitive transcription factor that regulates urogenital development and contributes to both nonsyndromic congenital malformations of the GU tract as well as the 16p11.2 phenotype.

The role of ascending aortic size in outcomes of patients with uncomplicated acute type B aortic dissection.

OBJECTIVE: Recent studies demonstrate that uncomplicated acute type B aortic dissection (uATBAD) patients with enlarged descending thoracic aortic diameters are at high risk for development of complications. This study aimed to determine the association of maximum ascending aortic diameter and area and outcomes in patients with uATBAD. METHODS: All patients admitted with uATBAD from June 2000 to January 2015 were reviewed, and those with available imaging were included. All measurements were obtained by a specialized cardiovascular radiologist, including the maximum ascending aortic diameter and area. Outcomes, including the need for intervention and mortality, were tracked over time. Data were analyzed by stratified Kaplan-Meier and multiple Cox regression analyses using SAS 9.4 software (SAS Institute, Cary, NC). RESULTS: During the study period, 298 patients with uATBAD were admitted, with 238 having available computed tomography and 131 having computed tomography angiography imaging and adequate follow-up available for analysis. The cohort had an average age of 60.96 ± 13.4 years (60% male, 53% white). Ascending aortic area >12.1 cm2 and ascending aortic diameter >40.8 mm were associated with subsequent arch and proximal progression necessitating open ascending aortic repair (P < .027 and P < .033, respectively). Ascending diameter >40.8 mm predicted lower intervention-free survival (P = .01). However, it failed to predict overall survival (P = .12). Ascending aortic area >12.1 cm2 predicted lower intervention-free survival (P = .005). However, this was not predictive of mortality (P = .08). Maximum aortic diameter along the length of the aorta >44 mm persisted as a risk factor for mortality (P < .001). Neither maximum ascending aortic diameter >40.8 mm (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.42-2.83; P = .85) nor area >12.1 cm2 (HR, 0.992; 95% CI, 0.38-2.61; P = .99) significantly predicted mortality when controlling for maximum aortic diameter along the length of the aorta >44 mm (HR, 7.34; 95% CI, 2.3-23.41; P < .001), diabetes mellitus (HR, 6.4; 95% CI, 2.17-18.93; P < .001), age (HR, 1.06/y; 95% CI, 1.03-1.10; P < .001), history of stroke (HR, 5.03; 95% CI, 1.52-16.63; P = .008), and syncope on admission (HR, 21.11; 95% CI, 2.3-193.84; P = .007). Ascending aortic diameter >40.8 mm (HR, 2.01; 95% CI, 1.03-3.95; P = .04) and maximum ascending aortic area >12.1 cm2 (HR, 1.988; 95% CI, 1.02-3.87; P = .04) on admission persisted as predictors of decreased intervention-free survival after controlling for maximum aortic diameter along the length of the aorta >44 mm (HR, 3.142; 95% CI, 1.47-6.83; P < .004), syncope on admission (HR, 26.3; 95% CI, 2.81-246; P < .004), and pleural effusion on admission (HR, 3.02; 95% CI, 1.58-5.77; P < .001). CONCLUSIONS: uATBAD patients with ascending aortic area >12.1 cm2 or maximum ascending aortic diameter >40.8 mm are at high risk for development of subsequent arch and proximal progression and may require closer follow-up or earlier intervention. Ascending aortic size (diameter and area) is predictive of decreased intervention-free survival in patients with uATBAD.

Peripheral artery endothelial function responses to altered shear stress patterns in humans.

NEW FINDINGS: What is the central question of this study? What is the effect of altered shear stress pattern, with or without concurrent neurohumoral and metabolic activation, on the acute endothelial function response assessed via brachial artery flow-mediated dilatation? What is the main finding and its importance? Despite generating distinctive shear stress patterns (i.e. increases in anterograde only, anterograde only with neurohumoral and metabolic activation, and both anterograde and retrograde), similar acute improvements were observed in the brachial artery flow-mediated dilatation response in all conditions, indicating that anterograde and/or turbulent shear stress might be the essential element to induce acute increases in endothelial function. ABSTRACT: Endothelial function is influenced by both the direction and the magnitude of shear stress. Acute improvements in endothelial function have mostly been attributed to increased anterograde shear, whereas results from many interventional models in humans suggest that enhancing shear stress in an oscillatory manner (anterograde and retrograde) might be optimal. Here, we determined the acute brachial artery shear stress (SS) and flow-mediated dilatation (FMD) responses to three shear-altering interventions [passive heat stress (HEAT), mechanical forearm compression (CUFF) and handgrip exercise (HGEX)] and examined the relationship between changes in oscillatory shear index (OSI) and changes in FMD. During separate visits, 10 young healthy men (22 ± 3 years old) underwent 10 min of HEAT, CUFF or HGEX in their left forearm. Anterograde and retrograde SS, Reynolds number, OSI and FMD were assessed at rest and during/after each intervention. Anterograde SS increased during all interventions in a stepwise manner (P < 0.05 between interventions), with the change in HGEX (∆37.7 ± 12.2 dyn cm-2 , P < 0.05) > CUFF (∆25.1 ± 11.9 dyn cm-2 , P < 0.05) > HEAT (∆14.5 ± 7.9 dyn cm-2 , P < 0.05). Retrograde SS increased during CUFF (∆-19.6 ± 4.3 dyn cm-2 , P < 0.05). Anterograde blood flow was turbulent (i.e. Reynolds number ≥ |2000|) during all interventions (P < 0.05). The relative FMD improved after all interventions (P = 0.01), and there was no relationship between ∆OSI and ∆FMD. We elicited changes in SS profiles including increased anterograde SS (HEAT and HGEX) and both increased anterograde and retrograde SS (CUFF); regardless of the SS pattern, FMD improved to the same extent. These findings suggest that the presence of anterograde and/or turbulent SS might be the key to optimizing endothelial function in acute assessment protocols.

Comparison between esophageal and intestinal temperature responses to upper-limb exercise in individuals with spinal cord injury.

STUDY DESIGN: Experimental study. OBJECTIVE: Individuals with spinal cord injuries (SCI) may present with impaired sympathetic control over thermoregulatory responses to environmental and exercise stressors, which can impact regional core temperature (Tcore) measurement. The purpose of this study was to investigate whether regional differences in Tcore responses exist during exercise in individuals with SCI. SETTING: Rehabilitation centre in Wakayama, Japan. METHODS: We recruited 12 men with motor-complete SCI (7 tetraplegia, 5 paraplegia) and 5 able-bodied controls to complete a 30-min bout of arm-cycling exercise at 50% V̇O2 peak reserve. Tcore was estimated using telemetric pills (intestinal temperature; Tint) and esophageal probes (Teso). Heat storage was calculated from baseline to 15 and 30 min of exercise. RESULTS: At 15 min of exercise, elevations in Teso (Δ0.39 ± 0.22 °C; P < 0.05), but not Tint (Δ0.04 ± 0.18 °C; P = 0.09), were observed in able-bodied men. At 30 min of exercise, men with paraplegia and able-bodied men both exhibited increases in Teso (paraplegia: Δ0.56 ± 0.30 °C, P < 0.05; able-bodied men: Δ0.60 ± 0.31 °C, P < 0.05) and Tint (paraplegia: Δ0.38 ± 0.33 °C, P < 0.05; able-bodied men: Δ0.30 ± 0.30 °C, P < 0.05). Teso began rising 7.2 min earlier than Tint (pooled, P < 0.01). Heat storage estimated by Teso was greater than heat storage estimated by Tint at 15 min (P = 0.02) and 30 min (P = 0.03) in men with paraplegia. No elevations in Teso, Tint, or heat storage were observed in men with tetraplegia. CONCLUSIONS: While not interchangeable, both Teso and Tint are sensitive to elevations in Tcore during arm-cycling exercise in men with paraplegia, although Teso may have superior sensitivity to capture temperature information earlier during exercise.

Influence of the neural microenvironment on prostate cancer.

BACKGROUND: Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. METHOD: We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy. RESULT: Bilateral denervation resulted in reduced tumor incidence and size in mice. Botox treatment in humans resulted in increased apoptosis of cancer cells in the Botox treated side. A similar denervation gene array profile was identified in tumors arising in denervated rodent prostates, in spinal cord injury patients and in the Botox treated side of patients. Denervation induced exhibited a signature gene profile, indicating translation and bioenergetic shutdown. Nerves also regulate basic cellular functions of non-neoplastic epithelial cells. CONCLUSION: Nerves play a role in the homeostasis of normal epithelial tissues and are involved in prostate cancer tumor survival. This study confirms that interactions between human cancer and nerves are essential to disease progression. This work may make a major impact in general cancer treatment strategies, as nerve/cancer interactions are likely important in other cancers as well. Targeting the neural microenvironment may represent a therapeutic approach for the treatment of human prostate cancer.

Cardiovascular aging and the microcirculation of skeletal muscle: using contrast-enhanced ultrasound.

Skeletal muscle is the largest and most important site of capillary-tissue exchange, especially during high-energy demand tasks such as exercise; however, information regarding the role of the microcirculation in maintaining skeletal muscle health is limited. Changes in microcirculatory function, as observed with aging, chronic and cardiovascular diseases, and exercise, likely precede any alterations that arise in larger vessels, although further investigation into these changes is required. One of the main barriers to addressing this knowledge gap is the lack of methodologies for quantifying microvascular function in vivo; the utilization of valid and noninvasive quantification methods would allow the dynamic evaluation of microvascular flow during periods of clinical relevance such as during increased demand for flow (exercise) or decreased demand for flow (disuse). Contrast-enhanced ultrasound (CEUS) is a promising noninvasive technique that has been used for diagnostic medicine and more recently as a complementary research modality to investigate the response of the microcirculation in insulin resistance, diabetes, and aging. To improve the reproducibility of these measurements, our laboratory has optimized the quantification protocol associated with a bolus injection of the contrast agent for research purposes. This brief report outlines the assessment of microvascular flow using the raw time-intensity curve incorporated into gamma variate response modeling. CEUS could be used to compliment any macrovascular assessments to capture a more complete picture of the aging vasculature, and the modified methods presented here provide a template for the general analysis of CEUS within a research setting.

Cardiac and haemodynamic influence on carotid artery longitudinal wall motion.

NEW FINDINGS: What is the central question of this study? Carotid artery longitudinal wall motion (CALM) is a bidirectional forward and backward motion of the arterial wall; however, there is no evidence in humans for what controls CALM despite proposals for pulse pressure, left ventricular motion and shear rate. What is the main finding and its importance? Carotid artery longitudinal wall motion responses were heterogeneous when manipulating sympathetic activation and endothelium-independent vasodilatation, leading to non-significant group responses. However, individual CALM responses were associated with left ventricular rotation and shear rate. These findings are important when interpreting changes in CALM in humans with acute or chronic experimental designs. Carotid artery longitudinal wall motion (CALM) has recently attracted interest as an indicator of arterial health; however, the regulation of CALM is poorly understood. We conducted a series of studies aimed at manipulating pulse pressure (PP), left ventricular (LV) motion and carotid shear rate, which have been previously suggested to regulate various components of CALM pattern and magnitude. To determine the regulatory influences on CALM, 15 healthy men (22 ± 2 years old) were exposed to three acute interventions: the serial subtraction test (SST); the cold pressor test (CPT); and exposure to sublingual nitroglycerine (NTG). The SST elicited increases in PP (P < 0.01), apical LV rotation (P < 0.01) and carotid shear rate (P < 0.01), with no changes in CALM (P > 0.05). Likewise, the CPT elicited increases in PP (P = 0.01), basal LV rotation (P = 0.04) and carotid shear rate (P = 0.01), with no changes in CALM (P > 0.05). Conversely, exposure to NTG elicited no change in PP (P = 0.22), basal (P = 0.65) or apical LV rotation (P = 0.45), but did decrease carotid shear rate (P < 0.01), without altering CALM (P > 0.05). Considerable individual variability in CALM responses prompted further analyses where all three interventions were pooled for change scores. Changes in LV basal rotation were related to changes in systolic retrograde CALM (B = -0.025, P = 0.03), whereas changes in carotid shear rate were related to changes in diastolic CALM displacement (B = 0.0009, P = 0.01). The interventions were underpinned by relationships between CALM and both LV basal rotation and local shear rate at the individual level, indicating that cardiac and haemodynamic factors may influence CALM in humans.

Assessing Ventilatory Threshold in Individuals With Motor-Complete Spinal Cord Injury.

OBJECTIVE: To assess the feasibility of measuring ventilatory threshold (VT) in higher-level motor-complete spinal cord injury (SCI) using 4 different analysis methods based on noninvasive gas exchange. DESIGN: Observational. SETTING: Laboratory testing. PARTICIPANTS: Individuals with C4-T6 motor-complete SCI (16 paraplegia, 22 tetraplegia; American Spinal Injury Association Impairment Scale A/B; 42±10 years old). INTERVENTIONS: Not applicable. MAIN OUTCOME: VT from a graded arm cycling test to volitional exhaustion using 4 methods: ventilatory equivalents, excess CO2, V-slope, and combined method. RESULTS: VT could be identified in all individuals with paraplegia, but in only 68% of individuals with tetraplegia. Individuals without observable VT completed the graded exercise test with lower ventilatory rate, peak power output, and peak oxygen consumption (Vo2peak) (all P<.05), compared to those with a detectable VT. Bland-Altman plots indicate minimal bias between methods (range: 0.01-0.03 L/min), with 95% limits of agreement of the difference within 0.25 L/min. Absolute V.o2 at VT with individual methods were all correlated to peak power output (r>0.74; P<.01) and Vo2peak (r>0.91; P<.01), with negligible differences between methods. CONCLUSIONS: The assessment of VT is a feasible alternative to peak exercise testing for aerobic fitness in individuals with higher-level, motor-complete SCI, although care should be taken when interpreting VT in individuals with tetraplegia who have lower cardiorespiratory fitness and lower peak power outputs.

Cardiovascular profile in postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome type III.

The cardiovascular profile of postural orthostatic tachycardia syndrome + Ehlers-Danlos syndrome hypermobility type (POTS + EDSIII) has not been described, despite suggestions that it plays a role in orthostatic intolerance. We studied nine individuals diagnosed with POTS + EDSIII and found that the arterial stiffness and cardiac profiles of patients with POTS + EDSIII were comparable to those of age- and sex-matched controls, suggesting an alternate explanation for orthostatic intolerance.

Defining and predicting 'intrauterine fetal renal failure' in congenital lower urinary tract obstruction.

BACKGROUND: The aim of this study was to identify predictors of 'intrauterine fetal renal failure' in fetuses with severe congenital lower urinary tract obstruction (LUTO). METHODS: We undertook a retrospective study of 31 consecutive fetuses with a diagnosis of LUTO in a tertiary Fetal Center between April 2013 and April 2015. Predictors of 'intrauterine fetal renal failure' were evaluated in those infants with severe LUTO who had either a primary composite outcome measure of neonatal death in the first 24 h of life due to severe pulmonary hypoplasia or a need for renal replacement therapy within 7 days of life. The following variables were analyzed: fetal bladder re-expansion 48 h after vesicocentesis, fetal renal ultrasound characteristics, fetal urinary indices, and amniotic fluid volume. RESULTS: Of the 31 fetuses included in the study, eight met the criteria for 'intrauterine fetal renal failure'. All of the latter had composite poor postnatal outcomes based on death within 24 h of life (n = 6) or need for dialysis within 1 week of life (n = 2). The percentage of fetal bladder refilling after vesicocentesis at time of initial evaluation was the only predictor of 'intrauterine fetal renal failure' (cut-off <27 %, area under the time-concentration curve 0.86, 95 % confidence interval 0.68-0.99; p = 0.009). CONCLUSION: We propose the concept of 'intrauterine fetal renal failure' in fetuses with the most severe forms of LUTO. Fetal bladder refilling can be used to reliably predict 'intrauterine fetal renal failure', which is associated with severe pulmonary hypoplasia or the need for dialysis within a few days of life.

Seated Elliptical Exercise, But Not Periodic Standing, Alleviates Sitting-Induced Changes to Arterial Wave Reflections.

PURPOSE: Sedentary behavior may contribute to increased central wave reflection due to associated peripheral vasoconstriction, yet its impact on central hemodynamics and the mitigating effects of interventional strategies have not been thoroughly investigated. We tested whether standing or seated elliptical breaks alleviate the deleterious effects of prolonged sitting on central wave reflections. METHODS: Eighteen healthy adults (9 9 females, 25 ± 3 yr) completed three 3-h protocols on separate days: uninterrupted sitting, sitting with periodic standing, and sitting with periodic seated elliptical activity. Central wave reflection, central pulse wave velocity, and lower-limb pulse wave velocity were measured before and after each intervention. RESULTS: Central relative wave reflection magnitude (RM) increased during sitting (0.31 ± 0.05 to 0.35 ± 0.05; P < 0.01) but did not change after standing (0.30 ± 0.05 to 0.32 ± 0.04; P = 0.19) or elliptical protocols (0.30 ± 0.05 to 0.30 ± 0.04; P > 0.99). The change in RM during prolonged sitting (ΔRM) was attenuated with elliptical activity (0.04 ± 0.05 vs 0.00 ± 0.03; P = 0.02) but not with periodic standing (0.04 ± 0.04 vs 0.02 ± 0.05; P = 0.54). In addition, augmentation index and central pulse wave velocity increased after sitting (both P < 0.01) and periodic standing (both P < 0.01) but were unchanged after elliptical activity. Lower limb pulse wave velocity did not change after sitting ( P = 0.73) or standing ( P = 0.21) but did decrease after elliptical activity ( P = 0.03). CONCLUSIONS: Prolonged sitting without interruptions increased central wave reflection, whereas elliptical but not standing interruptions were able to ameliorate multiple sitting-induced vascular consequences. More work is required to examine the long-term effectiveness of interruption strategies, as well as the optimal type, frequency, and duration for reducing vascular risk associated with sedentary behaviors.

The influence of physical activity and sex on carotid artery longitudinal wall motion in younger healthy adults.

Carotid artery longitudinal wall motion (CALM) is a novel preclinical marker for atherosclerosis that describes the axial anterograde and retrograde motion of the intima-media complex. While regular physical activity and sex are known to independently influence arterial stiffness, their roles on axial arterial wall behaviour are unknown. The purpose of this study is to examine whether physical activity and sex impact CALM. We hypothesized that CALM retrograde displacement and total amplitude would be greater in females and active individuals, as a function of arterial stiffness. Fifty-seven young healthy adults (30 females; aged 22 ± 3 years) were evaluated for CALM outcomes and arterial stiffness and grouped by physical activity based on active (V̇O2 = 44.2 ± 8.9 mL/kg/min) or sedentary (V̇O2 = 33.7 ± 6.7 mL/kg/min) lifestyles defined by the Canadian 24-Hour Movement Guidelines. Arterial stiffness and CALM were measured by carotid-femoral pulse wave velocity (cfPWV) and vascular ultrasound at the right common carotid artery with speckle tracking analysis, respectively. cfPWV was greater in males (p < 0.01) with no interaction between sex and physical activity (p = 0.90). CALM anterograde displacement was greater in males (p = 0.03) resulting in a forward shift in total CALM pattern, which became less prominent when controlling for mean arterial pressure (p = 0.06). All other CALM outcomes were not different between activity and sex. V̇O2max was not correlated to any CALM outcome (all p > 0.05). Apparent sex differences in vascular function extend to novel CALM outcomes but may be confounded by blood pressure. We recommend sex-balanced design and reporting in future studies due to possible anterograde-shifted CALM patterns in healthy males.

Impact of Ultrasound Scanning Plane on Common Carotid Artery Longitudinal Wall Motion.

OBJECTIVE: The arterial wall not only moves in the radial direction to expand circumferentially but also moves in the axial (longitudinal) direction in a predictable bidirectional pattern during a normal cardiac cycle. While common carotid artery (CCA) longitudinal wall motion (CALM) has been described previously, there is a lack of evidence-based method standardization to align practices for human measurement. The purpose of this study was to evaluate whether different scanning planes impact CALM outcomes in healthy males and females to provide clarity on data collection strategies. METHODS: Thirty-one healthy adults (16 females, 23 ± 3 y of age) underwent ultrasound scanning of the right CCA in the anterior, lateral, and posterior imaging planes. CALM was evaluated using a custom speckle-tracking algorithm and was analyzed as segmental motion outcomes (anterograde, retrograde, maximum displacement and radial-axial path length). RESULTS: No differences in any CALM outcome were observed between imaging planes (p > 0.05), and equivalence testing indicated that retrograde CALM displacement was similar between anterior and posterior distal walls (p = 0.04). We observed no differences (p > 0.05) in CALM outcomes between the proximal (free-wall, adjacent to the internal jugular vein [IJV]) and distal wall in the posterior imaging plane. Qualitatively, it was more difficult to successfully track vascular tissue between the IJV and CCA due to the thin wall components and highly mobile wall in the radial direction. CONCLUSION: In the absence of clear differences between scanning planes, we recommend standardizing acquisition in the lateral plane and avoiding the IJV free-wall when evaluating CALM in humans.

Supramaximal Testing to Confirm the Achievement of V̇O 2max in Acute Hypoxia.

PURPOSE: We sought to determine if supramaximal exercise testing confirms the achievement of V̇O 2max in acute hypoxia. We hypothesized that the incremental and supramaximal V̇O 2 will be sufficiently similar in acute hypoxia. METHODS: Twenty-one healthy adults (males n = 13, females n = 8) completed incremental and supramaximal exercise tests in normoxia and acute hypoxia (fraction inspired oxygen = 0.14) separated by at least 48 h. Incremental exercise started at 80 and 60 W in normoxia and 40 and 20 W in hypoxia for males and females, respectively, with all increasing by 20 W each minute until volitional exhaustion. After a 20-min postexercise rest period, a supramaximal test at 110% peak power until volitional exhaustion was completed. RESULTS: Supramaximal exercise testing yielded a lower V̇O 2 than incremental testing in hypoxia (3.11 ± 0.78 vs 3.21 ± 0.83 L·min -1 , P = 0.001) and normoxia (3.71 ± 0.91 vs 3.80 ± 1.02 L·min -1 , P = 0.01). Incremental and supramaximal V̇O 2 were statistically similar, using investigator-determined equivalence bounds ±150 mL·min -1 , in hypoxia ( P = 0.02, 90% confidence interval [CI] = 0.05-0.14) and normoxia ( P = 0.03, 90% CI = 0.01-0.14). Likewise, using ±2.1 mL·kg -1 ·min -1 bounds, incremental and supramaximal V̇O 2 values were statistically similar in hypoxia ( P = 0.04, 90% CI = 0.70-2.0) and normoxia ( P = 0.04, 90% CI = 0.30-2.0). CONCLUSIONS: Despite differences in the oxygen cascade, incremental and supramaximal V̇O 2 values were statistically similar in both hypoxia and normoxia, demonstrating the utility of supramaximal verification of V̇O 2max in the setting of acute hypoxia.

Mechanical ventilation in a conscious male during exercise: a case report.

We recently explored the cardiopulmonary interactions during partial unloading of the respiratory muscles during exercise. Expanding upon this work, we present a noteworthy case study whereby we eliminated the influence of respiration on cardiac function in a conscious but mechanically ventilated human during exercise. This human was a young healthy endurance-trained male who was mechanically ventilated during semi-recumbent cycle exercise at 75 Watts (W) (∼30% Wmax). During mechanically ventilated exercise, esophageal pressure was reduced to levels indistinguishable from the cardiac artefact which led to a 94% reduction in the power of breathing. The reduction in respiratory pressures and respiratory muscle work led to a decrease in cardiac output (-6%), which was due to a reduction in stroke volume (-13%), left ventricular end-diastolic volume (-15%), and left-ventricular end-systolic volume (-17%) that was not compensated for by heart rate. Our case highlights the influence of extreme mechanical ventilation on cardiac function while noting the possible presence of a maximal physiological limit to which respiration (and its associated pressures) impacts cardiac function when the power of breathing is maximally reduced.