Arterial function in response to a 50 km ultramarathon in recreational athletes.

This study was performed to determine whether prolonged endurance running results in acute endothelial dysfunction and wave-reflection, as endothelial dysfunction and arterial stiffness are cardiovascular risk factors. Vascular function (conduit artery/macrovascular and resistance artery/microvascular) was assessed in 11 experienced runners (8 males, 3 females) before, during and after a 50 km ultramarathon. Blood pressure (BP), heart rate (HR), wave reflection, augmentation index (AIx) and AIx corrected for HR (AIx75) were taken at all time points-Baseline (BL), following 10, 20, 30 and 40 km, 1 h post-completion (1HP) and 24 h post-completion (24HP). Flow-mediated dilatation (FMD) and inflammatory biomarkers were examined at BL, 1HP and 24HP. Reactive hyperaemia area under the curve (AUC) and shear rate AUC to peak dilatation were lower (∼75%) at 1HP compared with BL (P < 0.001 for both) and reactive hyperaemia was higher at 24HP (∼27%) compared with BL (P = 0.018). Compared to BL, both mean central systolic BP and mean central diastolic BP were 7% and 10% higher, respectively, following 10 km and 6% and 9% higher, respectively, following 20 km, and then decreased by 5% and 8%, respectively, at 24HP (P < 0.05 for all). AIx (%) decreased following 20 km and following 40 km compared with BL (P < 0.05 for both) but increased following 40 km when corrected for HR (AIx75) compared with BL (P = 0.02). Forward wave amplitude significantly increased at 10 km (15%) compared with BL (P = 0.049), whereas backward wave reflection and reflected magnitude were similar at all time points. FMD and baseline diameter remained similar. These data indicate preservation of macrovascular (endothelial) function, but not microvascular function resulting from the 50 km ultramarathon.

Effect of acute handgrip and aerobic exercise on wasted pressure effort and arterial wave reflections in healthy aging.

Aging increases arterial stiffness and wave reflections that augment left ventricular wasted pressure effort (WPE). A single bout of exercise may be effective at acutely reducing WPE via reductions in arterial wave reflections. In young adults (YA) acute aerobic exercise decreases, whereas handgrip increases, wave reflections. Whether acute exercise mitigates or exacerbates WPE and arterial wave reflection in healthy aging warrants further examination. The purpose of this study was to determine if there are age-related differences in WPE and wave reflection during acute handgrip and aerobic exercise. When compared with baseline, WPE increased substantially in older adults (OA) during handgrip (5,219 ± 2,396 vs. 7,019 ± 2,888 mmHg·ms, P < 0.001). When compared with baseline, there was a robust reduction in WPE in OA during moderate-intensity aerobic exercise (5,428 ± 2,084 vs. 3,290 ± 1,537 mmHg·ms, P < 0.001), despite absolute WPE remaining higher in OA compared with YA during moderate-intensity aerobic exercise (OA 3,290 ± 1,537 vs. YA 1,188 ± 962 mmHg·ms, P < 0.001). There was no change in wave reflection timing indexed to ejection duration in OA during handgrip (40 ± 6 vs. 38 ± 4%, P = 0.41) or moderate-intensity aerobic exercise (40 ± 5 vs. 42 ± 8%, P = 0.99). Conversely, there was an earlier return of wave reflection in YA during handgrip (60 ± 11 vs. 52 ± 6%, P < 0.001) and moderate-intensity aerobic exercise (59 ± 7 vs. 51 ± 9%, P < 0.001). Changes in stroke volume were not different between groups during handgrip (P = 0.08) or aerobic exercise (P = 0.47). The greater increase in WPE during handgrip and decrease in WPE during aerobic exercise suggest that aortic hemodynamic responses to acute exercise are exaggerated with healthy aging without affecting stroke volume.NEW & NOTEWORTHY We demonstrated that acute aerobic exercise attenuated, whereas handgrip augmented, left ventricular hemodynamic load from wave reflections more in healthy older (OA) compared with young adults (YA) without altering stroke volume. These findings suggest an exaggerated aortic hemodynamic response to acute exercise perturbations with aging. They also highlight the importance of considering exercise modality when examining aortic hemodynamic responses to acute exercise in older adults.

Second systolic peak in fetal middle cerebral artery Doppler after intrauterine transfusion.

OBJECTIVE: To evaluate functional relationship between fetal circulatory response to intrauterine transfusion (IUT) as a circulatory challenge and appearance of second systolic peak (P2) in middle cerebral artery (MCA) based on hemodynamic principles. METHODS: According to the concept of pulse wave (PW) propagation and reflection in adults, PWs arrive twice at cerebral circulation, as primary wave caused by left ventricle ejection and secondary after reflection in peripheral arteries. Thus adults show a biphasic contour of systolic blood flow in cerebral arteries. Similar waveforms may appear in fetal MCA-Doppler, as a response to IUT as a circulatory challenge. This is a proof-of-principle study, applying classical hemodynamic principles to fetal circulation. Accordingly, appearance of MCA-P2 may indicate vasoconstriction with increased PW reflection and timing of P2(Δt) should agree with the additional PW travel time down to reflection and return (Tr). To test this agreement, we searched our database for IUTs performed for severe fetal anemia, and compared Δt, obtained by Doppler, with Tr, obtained by hemodynamic calculation using human fetal data. Level of agreement was assessed using Bland-Altman-Plots. RESULTS: We identified 21 fetuses with adequate Doppler quality for Δt evaluation. In four cases (19%) MCA-P2 was observed before the intervention, and in 17 interventions (81%) thereafter; a highly significant association between IUT and P2 appearance (p < 0.001). In these 17 interventions good agreement of P2 timing was found between Doppler assessment: Δt = 80 ± 8 ms, and hemodynamic calculation: Tr = 76 ± 4 ms. CONCLUSION: P2 appearance in fetal MCA-Doppler seems to indicate PW reflection due to increased vasoconstriction after IUT. Thus hemodynamic considerations might enable Doppler monitoring of fetal vasoconstriction.

Optimized design of an arterial network model reproduces characteristic central and peripheral haemodynamic waveform features of young adults.

The arterial network in healthy young adults is thought to be structured to optimize wave reflection in the arterial system, producing an ascending aortic pressure waveform with three key features: early systolic peak, negative systolic augmentation and diastolic hump. One-dimensional computer models have provided significant insights into arterial haemodynamics, but no previous models of the young adult have exhibited these three features. Given that this issue was likely to be related to unrepresentative or non-optimized impedance properties of the model arterial networks, we developed a new 'YoungAdult' model that incorporated the following features: (i) a new and more accurate empirical equation for approximating wave speeds, based on area and relative distance to elastic-muscular arterial transition points; (ii) optimally matched arterial junctions; and (iii) an improved arterial network geometry that eliminated 'within-segment' taper (which causes wave reflection in conduit arteries) whilst establishing 'impedance-preserving' taper. These properties of the model led to wave reflection occurring predominantly at distal vascular beds, rather than in conduit arteries. The model predicted all three typical characteristics of an ascending aortic pressure waveform observed in young adults. When compared with non-invasively acquired pressure and velocity measurements (obtained via tonometry and Doppler ultrasound in seven young adults), the model was also shown to reproduce the typical waveform morphology observed in the radial, brachial, carotid, temporal, femoral and tibial arteries. The YoungAdult model provides support for the concept that the arterial tree impedance in healthy young adults is exquisitely optimized, and it provides an important baseline model for investigating cardiovascular changes in ageing and disease states. KEY POINTS: The origin of wave reflection in the arterial system is controversial, but reflection properties are likely to give rise to characteristic haemodynamic features in healthy young adults, including an early systolic peak, negative systolic augmentation and diastolic hump in the ascending aortic pressure waveform, and triphasic velocity profiles in peripheral arteries. Although computational modelling provides insights into arterial haemodynamics, no previous models have predicted all these features. An established arterial network model was optimized by incorporating the following features: (i) a more accurate representation of arterial wave speeds; (ii) precisely matched junctions; and (iii) impedance-preserving tapering, thereby minimizing wave reflection in conduit arteries in the forward direction. Comparison with in vivo data (n = 7 subjects) indicated that the characteristic waveform features in young adults were predicted accurately. Our findings strongly imply that a healthy young arterial system is structured to optimize wave reflection in the main conduit arteries and that reflection of forward waves occurs primarily in the vicinity of vascular beds.

When right ventricular pressure meets volume: The impact of arrival time of reflected waves on right ventricle load in pulmonary arterial hypertension.

Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. A larger volume at a given pressure generates more wall tension. Return of reflected waves early after the onset of contraction, when RV volume is larger, may augment RV load. We aimed to elucidate: (1) the distribution of arrival times of peak reflected waves in treatment-naïve PAH patients; (2) the relationship between time of arrival of reflected waves and RV morphology; and (3) the effect of PAH treatment on the arrival time of reflected waves. Wave separation analysis was conducted in 68 treatment-naïve PAH patients. In the treatment-naïve condition, 54% of patients had mid-systolic return of reflected waves (defined as 34-66% of systole). Despite similar pulmonary vascular resistance (PVR), patients with mid-systolic return had more pronounced RV hypertrophy compared to those with late-systolic or diastolic return (RV mass/body surface area; mid-systolic return 54.6 ± 12.6 g m-2 , late-systolic return 44.4 ± 10.1 g m-2 , diastolic return 42.8 ± 13.1 g m-2 ). Out of 68 patients, 43 patients were further examined after initial treatment. At follow-up, the stiffness of the proximal arteries, given as characteristic impedance, decreased from 0.12 to 0.08 mmHg s mL-1 . Wave speed was attenuated from 13.3 to 9.1 m s-1 , and the return of reflected waves was delayed from 64% to 71% of systole. In conclusion, reflected waves arrive at variable times in PAH. Early return of reflected waves was associated with more RV hypertrophy. PAH treatment not only decreased PVR, but also delayed the timing of reflected waves. KEY POINTS: Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. Larger volume at a given pressure causes larger RV wall tension. Early return of reflected waves adds RV pressure in early systole, when RV volume is relatively large. Thus, early return of reflected waves may increase RV wall tension. Wave reflection can provide a description of RV load. In PAH, reflected waves arrive back at variable times. In over half of PAH patients, the RV is exposed to mid-systolic return of reflected waves. Mid-systolic return of reflected waves is related to RV hypertrophy. PAH treatment acts favourably on the RV not only by reducing resistance, but also by delaying the return of reflected waves. Arrival timing of reflected waves is an important parameter for understanding the relationship between RV load and its function in PAH.

[Quantitative analysis of the effect of contact pressure on the reflection characteristics of radial pressure wave].

The radial artery pulse wave contains a wealth of physiological and pathological information about the human body, and non-invasive studies of the radial artery pulse wave can assess arterial vascular elasticity in different age groups.The piezoelectric pulse wave transducers were used to non-invasively acquire radial artery pulse waves at different contact pressures in young and middle-aged and elderly populations. The radial artery waveforms were decomposed using a triangular blood flow model fitting method to obtain forward and reflected waves and calculate reflection parameters. Finally a correlation analysis and regression analysis of the contact pressure Psensor with the reflection parameters was carried out. The results showed that the reflection parameters RM, RI and Rd had a strong negative correlation with Psensor in both types of subjects, and the correlation coefficients and slopes of the regression curves were significantly different between the two types of subjects (P<0.05). Based on the results of this study, excessive contact pressure on the transducer should be avoided when detecting radial artery reflection waves in clinical practice. The results also show that the magnitude of the slope of the regression curve between the reflection parameters and the transducer contact pressure may be a potentially useful indicator for quantifying the elastic properties of the vessel.

Lower-body dynamic exercise reduces wave reflection in healthy young adults.

NEW FINDINGS: What is the central question of this study? There is a paradoxical reduction in augmentation index during lower-body dynamic (LBD) exercise in the face of an increase in central pressure. To determine causality, the amplitudes of forward and backward pressure waves were assessed separately using wave separation analysis. What is the main finding and its importance? Reflection magnitude decreased during LBD exercise in healthy young adults and was attributable to an increased forward pressure wave amplitude and decreased backward pressure wave amplitude. This vasoactive response might limit the adverse effects of wave reflection during LBD exercise, optimizing ventricular-arterial interactions. ABSTRACT: Acute lower-body dynamic (LBD) exercise decreases surrogate measures of wave reflection, such as the augmentation index. However, the augmentation index is influenced by the combined effects of wave reflection timing, magnitude and other confounding factors external to wave reflection, which make it difficult to discern the origin of changes in surrogate measures. The relative contributions of forward (Pf) and backward (Pb) pressure wave amplitudes to central pressure can be determined by wave separation analysis. Reflection magnitude (RM = Pb/Pf) and the timing of apparent wave reflection return can also be determined. We tested the hypothesis that acute LBD exercise decreases RM and reflected wave transit time (RWTT). Applanation tonometry was used to record radial artery pressure waveforms in 25 adults (24 ± 4 years of age) at baseline and during light-, moderate- and vigorous-intensity exercise. Wave separation analysis was conducted offline using a personalized physiological flow wave to determine Pf, Pb, RM and RWTT. The RM decreased during all intensities of exercise compared with baseline (all P < 0.001; baseline, 43 ± 5%; light, 33 ± 6%; moderate, 23 ± 7%; vigorous, 17 ± 5%). The reduction in RM was attributable to the combined effect of increased Pf and decreased Pb during exercise. The RWTT decreased during all intensities of exercise compared with baseline (all P < 0.04; baseline, 156 ± 17 ms; light, 144 ± 15 ms; moderate, 129 ± 16 ms; vigorous, 121 ± 17 ms). Lastly, in a stepwise multilinear regression, Pf, but not Pb and RWTT, contributed to increased central pulse pressure during LBD exercise. These data show that wave reflection decreased and that central pulse pressure is most influenced by Pf during LBD exercise.

Associations of dietary patterns with blood pressure and markers of subclinical arterial damage in adults with risk factors for CVD.

OBJECTIVE: Unhealthy diet is a modifiable risk factor leading to subclinical arterial damage (SAD), high BP and CVD. It was aimed to investigate the possible associations of dietary patterns (DPs) with SAD in adults having multiple CVD risk factors. DESIGN: Dietary intake was evaluated through two 24-h dietary recalls and principal component analysis was used to identify DPs. Oscillometry, applanation tonometry with pulse wave analysis and carotid ultrasound were used to assess peripheral and aortic BP, arterial stiffness and pressure wave reflections. SETTING: Laiko University Hospital, Athens, Greece. PARTICIPANTS: A total of 470 individuals (53·1 ± 14·2 years) with CVD risk factors were enrolled. RESULTS: A pattern characterised by increased consumption of whole-grain cereals, white meat and reduced consumption of sugar was positively associated with common carotid compliance (ß = 0·01, 95 % CI 0·00, 0·01), whereas a pattern high in refined cereals, red and processed meat was positively associated with brachial but not aortic systolic pressure (ß = 1·76, 95 % CI 0·11, 3·42) and mean arterial pressure (MAP) (ß = 1·18, 95 % CI 0·02, -2·38). Low consumption of low-fat dairy products, high consumption of full-fat cheese and butter was positively associated with MAP (ß = 0·97, 95 % CI 0·01, 1·95). Increased consumption of vegetables, fruits, fresh juices, fish and seafood was inversely associated with augmentation index (AIx) (ß = -1·01, 95 % CI -1·93, -0·09). CONCLUSION: Consumption of whole grains, white meat, fruits/vegetables, fish/seafood and avoidance of sugar was associated with improved SAD. Preference in refined grains, red/processed meat, high-fat cheese/butter and low intake of low-fat dairy products were associated with BP elevation. Future studies are needed to confirm the present findings.

Caffeine ingestion alters central hemodynamics following aerobic exercise in middle-aged men.

PURPOSE: To examine the acute influence of caffeine on post-exercise central blood pressures, arterial stiffness, and wave reflection properties. METHODS: In a double-blind randomized placebo-controlled crossover study design, ten middle-aged males (55 ± 5 year) completed two exercise trials after ingestion of caffeine (400 mg) or placebo. Measurements were taken before and 30 min post-ingestion via cuff-based pulse wave analysis (PWA) and carotid-femoral pulse wave velocity (PWV). Participants performed a 40-min cycling bout at 70% HRmax with matched workloads between trials. PWA and PWV were reassessed 30 min post-exercise. RESULTS: Prior to exercise, compared to placebo, caffeine increased brachial systolic blood pressure (bSBP) (+ 12.3 ± 2.4 mmHg; p = 0.004), brachial diastolic blood pressure (bDBP) (+ 7.7 ± 0.9 mmHg; p = 0.011), central systolic blood pressure (cSBP) (+ 11.1 ± 2.1 mmHg; p = 0.005) and central diastolic blood pressure (cDBP) (+ 7.6 ± 1.0 mmHg; p = 0.012). PWV was higher 30 min after pill ingestion (p = 0.021 for time) with a trend for a greater increase in caffeine (p = 0.074 for interaction). bSBP (p = 0.036) and cSBP (p = 0.007) were lower after exercise but remained higher (both p < 0.001) in caffeine compared to placebo. PWV remained higher (p = 0.023) after exercise in caffeine compared to placebo but was not influenced by exercise. At rest, augmentation pressure (AP) and index (AIx) were not influenced by caffeine ingestion. Conversely, AIx was lower (p = 0.009) after exercise in placebo only. CONCLUSION: In healthy and active middle-aged men, pre-exercise caffeine ingestion led to higher central and peripheral systolic blood pressures, PWV and AIx at 30 min post-exercise, indicating an increased left ventricular workload which may have implications for cardiovascular event risk.

The association of waterpipe smoking with arterial stiffness and wave reflection in a community-based sample.

PURPOSE: The evidence linking waterpipe smoking to cardiovascular disease is limited. We evaluated the association of waterpipe smoking (WPS) with arterial stiffness and wave reflection measured by augmentation pressure (AP), augmentation index (AIx), and carotid-femoral pulse wave velocity (CFPWV), which are validated predictors of cardiovascular disease. MATERIALS AND METHODS: Community-based, cross-sectional study including 205 exclusive waterpipe smokers and 199 matched never-smokers aged 35 years or older (mean age 51.7 ± 8.9 years, 36% females). Smoking and its extent were assessed using a validated questionnaire and urine cotinine levels. CFPWV, AP, AIx (AP/aortic pulse pressure) and heart rate adjusted AIx (AIx@75) were determined using tonometry and compared between smokers and non-smokers, and the association of WPS with tonometry measures was assessed using linear regression adjusting for possible confounders. RESULTS: Waterpipe smokers and non-smokers had similar mean age and sex distribution. Compared to non-smokers, waterpipe smokers had significantly higher adjusted AP (10.5 ± 3.9 vs. 9.4 ± 3.9 mmHg respectively; p = 0.01), AIx (28.1 ± 8.4 vs. 25.7 ± 8.5% respectively; p = 0.01) and AIx@75 (24.2 ± 8.7 vs. 21.8 ± 8.9% respectively; p = 0.01). AIx was significantly associated with WPS extent, measured by a number of waterpipe smoked/day (ß = 1.04/waterpipe, 95%CI:[0.50-1.58]), duration of waterpipe smoking (ß = 0.77/10-years, 95%CI:[0.16-1.38]), their products in waterpipe-years (ß = 0.30/10-waterpipe-year, 95%CI:[0.12-0.47]) and plasma cotinine (ß = 0.56/100 ng/ml, 95%CI:[0.14-0.98]), adjusting for possible confounders, and so were AP and AIx@75. CFPWV however, was not associated with waterpipe smoking. CONCLUSION: In a community-based sample, exclusive WPS and its extent were associated with a dose-dependent increase in AIx and AP, accounting for other risk factors, suggesting that waterpipe smokers are at increased risk of cardiovascular disease.

Central Haemodynamics Are Associated With Pulmonary Function in Postmenopausal Women.

PURPOSE: Increased arterial stiffness predicts cardiovascular disease, which is associated with deteriorated pulmonary function and worsened chronic obstructive pulmonary disease. The present study examined whether arterial function was associated with pulmonary function in postmenopausal women. METHODS: This study evaluated 41 postmenopausal women (age range: 59-85 years). Arterial function was measured as central systolic blood pressure (cSBP), central pulse pressure (cPP), brachial systolic BP (bSBP), brachial diastolic BP (bDBP), brachial PP (bPP), brachial mean arterial pressure (bMAP) and the augmentation index (AIx). AIx was adjusted for a heart rate of 75 beats per minute (bpm) (AIx@75) and served as the index of arterial stiffness determined by the reflected wave at the central artery. Pulmonary function was measured as forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and the FEV1/FVC ratio. RESULTS: Univariate regression analysis demonstrated that cPP, bDBP and bPP were correlated with FVC and FEV1 (p<0.05, respectively), while AI@75 was correlated with FVC, FEV1 and FEV1/FVC ratio (p<0.01, respectively). A stepwise multivariate regression analysis revealed that bDBP was independently associated with FVC (p=0.032), while AI@75 was independently associated with FVC, FEV1 and FEV1/FVC ratio (p=0.001, p=0.003 and p=0.017, respectively). The FVC, FEV1 and FEV1/FVC ratio were lower in participants with a high AIx versus with a low AIx (p=0.0001, p=0.001 and p=0.044, respectively). CONCLUSION: These results suggest that increased AIx is associated with lower pulmonary function in postmenopausal women.

Central Over Peripheral Blood Pressure: An Emerging Issue in Hypertension Research.

Measurement of blood pressure is one of the most important and powerful clinical tools in clinical practice. Physicians use the classical method that was introduced more than 100 years ago with the emergence of the brachial cuff sphygmomanometer. The use of this method, despite its initial setbacks, spread like fire throughout the medical community with the boost by the early adoption by insurance companies to assess risk as well as the ease of use, the availability with the wide variety of devices, the good reproducibility and its predictive role. However, a long-forgotten dispute between measurements of peripheral (brachial) and central (aortic, carotid) blood pressure has resurfaced after the introduction of techniques and devices that can easily and accurately estimate non-invasively the central pressure waveform. Clinicians, until recently, focussed only on the pressure waveform trough (diastole) and peak (systole), ignoring the possible information provided by the rest of the arterial pressure waveform. Several restrictions exist with peripheral blood pressures measured with either an oscillometric or a sphygmomanometer device that blur the existing image of the ideal biomarker to describe the haemodynamic characteristics of the cardiovascular system. On the other hand, central pressures seem to be more pathophysiologically relevant to end-organ damage of the brain, heart and kidneys and on future events. Furthermore, measurement of the central waveform can provide clinically useful information, like the quantification of wave reflections with augmentation index, beyond blood pressure measured in the brachial artery. This article will explain the pathophysiological mechanisms linking central pressures to cardiovascular outcomes, review the evidence for the use of central blood pressure over peripheral pressures, elaborate on the prognostic role of central blood pressures and finally review the latest developments on the pharmacological modulation of central blood pressures.

Vascular Responses to High-Intensity Battling Rope Exercise between the Sexes.

The purpose of the study was to assess high-intensity battling rope exercise (HI-BRE) on hemodynamics, pulse wave reflection and arterial stiffness during recovery and between sexes. Twenty-three young, healthy resistance-trained individuals (men: n = 13; women: n = 10) were assessed for all measures at Rest, as well as 10-, 30-, and 60-minutes following HI-BRE. A one-way repeated measures ANOVA was used to analyze the effects of HI-BRE across time (Rest, 10, 30, and 60-minutes) on all dependent variables. Significant main effects were analyzed using paired t-tests with a Sidak correction factor. Significance was accepted a priori at p 0.05. There were significant reductions in hemodynamic measures of diastolic blood pressure (BP) in women, but not men following HI-BRE at 30 minutes. Further, measures of pulse wave reflection, specifically those of the augmentation index (AIx) and wasted left ventricular energy (ΔEw), were significantly increased in both men and women for 60 minutes, but changes were significantly attenuated in women suggesting less ventricular work. There were also significant increases in arterial stiffness in regard to the aorta and common carotid artery that were fully recovered by 30 and 60 minutes, respectively with no differences between men and women. Thus, the primary findings of this study suggest that measures of hemodynamics and pulse wave reflection are collectively altered for at least 60 minutes following HI-BRE, with women having attenuated responses compared to men.

Conduit arterial wave reflection promotes pressure transmission but impedes hydraulic energy transmission to the microvasculature.

Current thinking suggests that wave reflection in arteries limits pulse pressure and hydraulic energy (HE) transmission to the microvasculature and that this protective effect reduces with advancing age. However, according to transmission line theory, pressure transmission (Tp) and reflection (R) coefficients are proportional (Tp = 1 + R), implying that wave reflection would promote rather than limit pressure transmission. We hypothesized that increasing distal pulse pressure (PPd) with age is instead related to increased proximal pulse pressure (PPp) and its forward component and that these are modulated by arterial compliance. A one-dimensional model of a fractal arterial tree containing 21 generations was constructed. Wave speed in each vessel was prescribed to achieve a uniform R at every junction, with changes in R achieved by progressively stiffening proximal or distal vessels. For both stiffening scenarios, decreasing reflection led to a decrease or no change in PPd when forward pressure or compliance were held constant, respectively, suggesting that wave reflection per se does not limit pressure transmission. Proximal pulse pressure, its forward component, and PPd increased with decreasing compliance; furthermore, proximal and distal pulse pressures were approximately proportional. With fixed compliance but decreasing reflection, HE transmission increased, whereas pressure transmission decreased, consistent with transmission line theory. In conclusion, wave reflection does not protect the microvasculature from high PPd; rather, PPp and PPd are modulated by arterial compliance, which reduces with age. Wave reflection has opposing effects on pressure and HE transmission; hence, the relative importance of pressure versus HE in contributing to microvascular damage warrants investigation.NEW & NOTEWORTHY With aging, a reduction in the stiffness gradient between elastic and muscular arteries is thought to reduce wave reflection in conduit arteries, leading to increased pulsatile pressure transmission into the microvasculature. This assumes that wave reflection limits pressure transmission in arteries. However, using a computational model, we showed that wave reflection promotes pulsatile pressure transmission, although it does limit hydraulic energy transmission. Increased microvascular pulse pressure with aging is instead related to decreasing arterial compliance.

Early return of reflected waves increases right ventricular wall stress in chronic thromboembolic pulmonary hypertension.

Pulmonary vascular resistance (PVR) and compliance are comparable in proximal and distal chronic thromboembolic pulmonary hypertension (CTEPH). However, proximal CTEPH is associated with inferior right ventricular (RV) adaptation. Early wave reflection in proximal CTEPH may be responsible for altered RV function. The aims of the study are as follows: 1) to investigate whether reflected pressure returns sooner in proximal than in distal CTEPH and 2) to elucidate whether the timing of reflected pressure is related to RV dimensions, ejection fraction (RVEF), hypertrophy, and wall stress. Right heart catheterization and cardiac MRI were performed in 17 patients with proximal CTEPH and 17 patients with distal CTEPH. In addition to the determination of PVR, compliance, and characteristic impedance, wave separation analysis was performed to determine the magnitude and timing of the peak reflected pressure (as %systole). Findings were related to RV dimensions and time-resolved RV wall stress. Proximal CTEPH was characterized by higher RV volumes, mass, and wall stress, and lower RVEF. While PVR, compliance, and characteristic impedance were similar, proximal CTEPH was related to an earlier return of reflected pressure than distal CTEPH (proximal 53 ± 8% vs. distal 63 ± 15%, P < 0.05). The magnitude of the reflected pressure waves did not differ. RV volumes, RVEF, RV mass, and wall stress were all related to the timing of peak reflected pressure. Poor RV function in patients with proximal CTEPH is related to an early return of reflected pressure wave. PVR, compliance, and characteristic impedance do not explain the differences in RV function between proximal and distal CTEPH.NEW & NOTEWORTHY In chronic thromboembolic pulmonary hypertension (CTEPH), proximal localization of vessel obstructions is associated with poor right ventricular (RV) function compared with distal localization, though pulmonary vascular resistance, vascular compliance, characteristic impedance, and the magnitude of wave reflection are similar. In proximal CTEPH, the RV is exposed to an earlier return of the reflected wave. Early wave reflection may increase RV wall stress and compromise RV function.

Reflected hemodynamic waves influence the pattern of Doppler ultrasound waveforms along the umbilical arteries.

The pulsatile pattern of blood motion measured by Doppler ultrasound within the umbilical artery is known to contain useful diagnostic information and is widely used to monitor pregnancies at risk of fetal growth restriction or stillbirth. Animal studies have identified reflected pressure waves traveling counter to the direction of blood flow as an important factor in the shape of these waveforms. In the present study, we establish a method to measure reflected waves in the human umbilical artery and assess their influence on blood velocity pulsation. Ninety-five pregnant women were recruited from a general obstetrics clinic between 26 and 37 wk of gestation and examined by Doppler ultrasound. Blood velocity waveforms were recorded for each umbilical artery at three locations along the umbilical cord. With the use of a computational procedure, a pair of forward and reverse propagating waves was identified to explain the variation in observed Doppler ultrasound waveforms along the cord. Among the data sets that met data quality requirements, waveforms in 93 of the 130 arteries examined agreed with the wave reflection model to within 1.5% and showed reflections ranging in magnitude from 3 to 52% of the forward wave amplitude. Strong reflections were associated with large differences in pulsatility between the fetal and placental ends of the cord. As reflections arise from transitions in the biomechanical properties of blood vessels, these observations provide a plausible mechanism for the link between abnormal waveforms and clinically significant placental pathology and could lead to more precise screening methods for detecting pregnancies complicated by placental disease. NEW & NOTEWORTHY The pulsatile pattern of blood motion measured by Doppler ultrasound within the umbilical artery is known to contain useful diagnostic information and is widely used to monitor pregnancies at risk of fetal growth restriction. We demonstrate based on a study of 95 pregnant women that the shape of these umbilical artery waveforms is explained by the presence of a reflected pressure wave traveling counter to the direction of blood flow.

Placental vascular abnormalities in the mouse alter umbilical artery wave reflections.

Current methods to detect placental vascular pathologies that monitor Doppler ultrasound changes in umbilical artery (UA) pulsatility have only moderate diagnostic utility, particularly in late gestation. In fetal mice, we recently demonstrated that reflected pressure waves propagate counter to the direction of flow in the UA and proposed the measurement of these reflections as a means to detect abnormalities in the placental circulation. In the present study, we used this approach in combination with microcomputed tomography to investigate the relationship between altered placental vascular architecture and changes in UA wave reflection metrics. Fetuses were assessed at embryonic day (E) 15.5 and E17.5 in control C57BL6/J mice and dams treated with combination antiretroviral therapy (cART), a known model of fetal growth restriction. Whereas the reflection coefficient was not different between groups at E15.5, it was 27% higher at E17.5 in cART-treated mice compared with control mice. This increase in reflection coefficient corresponded to a 36% increase in the total number of vessel segments, a measure of overall architectural complexity. Interestingly, there was no difference in UA pulsatility index between groups, suggesting that the wave reflections convey information about vascular architecture that is not captured by conventional ultrasound metrics. The wave reflection parameters were found to be associated with the morphology of the fetoplacental arterial tree, with the area ratio between the UA and first branch points correlating with the reflection coefficient. This study highlights the potential for wave reflection to aid in the noninvasive clinical assessment of placental vascular pathology. NEW & NOTEWORTHY We used a novel ultrasound methodology based on detecting pulse pressure waves that propagate along the umbilical artery to investigate the relationship between changes in wave reflection metrics and altered placental vascular architecture visualized by microcomputed tomography. Using pregnant mice treated with combination antiretroviral therapy, a model of fetal growth restriction, we demonstrated that reflections in the umbilical artery are sensitive to placental vascular abnormalities and associated with the geometry of the fetoplacental tree.

Impact of pulmonary endarterectomy on pulmonary arterial wave propagation and reservoir function.

High wave speed and large wave reflection in the pulmonary artery have previously been reported in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We assessed the impact of pulmonary endarterectomy (PEA) on pulmonary arterial wave propagation and reservoir function in patients with CTEPH. Right heart catheterization was performed using a combined pressure and Doppler flow sensor-tipped guidewire to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery in eight patients with CTEPH before and 3 mo after PEA. Wave intensity and reservoir-excess pressure analyses were then performed. Following PEA, mean pulmonary arterial pressure (PAPm; ∼49 vs. ∼32 mmHg), pulmonary vascular resistance (PVR; ∼11.1 vs. ∼5.1 Wood units), and wave speed (∼16.5 vs. ∼8.1 m/s), i.e., local arterial stiffness, markedly decreased. The changes in the intensity of the reflected arterial wave and wave reflection index (pre: ∼28%; post: ∼22%) were small, and patients post-PEA with and without residual pulmonary hypertension (i.e., PAPm ≥ 25 mmHg) had similar wave reflection index (∼20 vs. ∼23%). The reservoir and excess pressure decreased post-PEA, and the changes were associated with improved right ventricular afterload, function, and size. In conclusion, although PVR and arterial stiffness decreased substantially following PEA, large wave reflection persisted, even in patients without residual pulmonary hypertension, indicating lack of improvement in vascular impedance mismatch. This may continue to affect the optimal ventriculoarterial interaction, and further studies are warranted to determine whether this contributes to persistent symptoms in some patients.NEW & NOTEWORTHY We performed wave intensity analysis in the pulmonary artery in patients with chronic thromboembolic pulmonary hypertension before and 3 mo after pulmonary endarterectomy. Despite substantial reduction in pulmonary arterial pressures, vascular resistance, and arterial stiffness, large pulmonary arterial wave reflection persisted 3 mo postsurgery, even in patients without residual pulmonary hypertension, suggestive of lack of improvement in vascular impedance mismatch.

Effect of maternal betamethasone administration on feto-placental vascular resistance in the mouse†.

Antenatal corticosteroids are often administered to women at risk of preterm birth to accelerate fetal lung development; however, there is evidence that this treatment may adversely affect placental function in some fetuses. Our group has recently demonstrated that wave reflections in the umbilical artery (UA), measured using high-frequency ultrasound, are sensitive to placental vascular abnormalities. In the present study, we used this approach to investigate the effect of maternal administration of betamethasone, a clinically relevant corticosteroid, on the feto-placental vasculature of the mouse. Fetuses were assessed at embryonic day (E)15.5 and E17.5 in C57BL6/J mice. At both gestational ages, the UA diameter, UA blood flow, and the wave reflection coefficient were significantly elevated in the betamethasone-treated mice compared to vehicle-treated controls. These observations support the interpretation that placental vascular resistance dropped with betamethasone treatment to an extent that could not be explained by vasodilation of the UA alone. Consistent with clinical studies, the effect of betamethasone on UA end-diastolic velocity was heterogeneous. Our results suggest that UA wave reflections are more sensitive to acute changes in placental vascular resistance compared with the UA pulsatility index, and this technique may have clinical application to identify a favorable placental vascular response to fetal therapies such as antenatal corticosteroids, where the fetal heart rate is likely to vary.

Heart Failure-Specific Relationship Between Muscle Sympathetic Nerve Activity and Aortic Wave Reflection.

BACKGROUND: Reflected arterial waves contribute to left ventricular (LV) afterload. Heart failure patients with reduced ejection fraction (HFrEF) are afterload sensitive and sympathetically activated. We tested the hypothesis that HFrEF patients exhibit a positive relationship between sympathetic vasoconstrictor discharge and aortic wave reflection. METHODS: Sixteen treated patients with HFrEF (61 ± 9 years of age, left ventricular ejection fraction 30 ± 7%, 3 women) and 16 similar-aged healthy control subjects (57 ± 7 years of age, 4 women) underwent noninvasive measurements of radial pulse waveforms (applanation tonometry) to calculate central blood pressures and aortic wave reflection characteristics: augmentation pressure (AP), augmentation index (AIx), and AIx corrected to a heart rate of 75 beats/min (AIx@75). Muscle sympathetic nerve activity (MSNA) burst frequency was recorded from the fibular nerve (microneurography). RESULTS: HFrEF patients had higher AIx (26 ± 9 vs 17 ± 15%; P < .05) and MSNA burst frequency (48 ± 7 vs 39 ± 11 bursts/min; P < .05) and lower central diastolic pressure than control subjects (64 ± 8 vs 70 ± 9 mm Hg; P = 0.05). There were no between-group differences in heart rate, other measures of blood pressure (brachial and central; P > .05), AP (11 ± 5 vs 7 ± 8 mm Hg; P = 0.11), or AIx@75 (19 ± 9 vs 13 ± 11%,-P = 0.14). MSNA correlated positively with AP (r = 0.50; P < .05), AIx (r = 0.51; P < .05), and AIx@75 (r = 0.54; P < .05) in HFrEF patients but not in control subjects (r = 0.002-0.18; P > 0.49). CONCLUSIONS: In patients with HFrEF, but not similarly aged healthy subjects, indices of aortic wave reflection correlate positively with MSNA. By increasing LV afterload, such neurovascular coupling could impair LV performance and worsen heart failure symptoms. Therapies that attenuate neurogenic vasoconstriction may benefit HFrEF patients by diminishing arterial wave reflection.