Citations

Increased arterial stiffness is an early indicator of various cardiovascular diseases (CVD). Arterial Dispersion Ultrasound Vibrometry (ADUV) employs acoustic radiation force to induce arterial wall motion, enabling estimation of arterial wave velocity (i.e., phase velocity). This study investigates the correlation between ADUV-derived wave velocity and traditional arterial stiffness metrics, including distensibility, compliance, and stiffness index in the right and left common carotid arteries (CCAs). In a cohort of 59 subjects, categorized as (a) confirmed CVD (n = 27), (b) individuals with cardiovascular risk factors (n = 20), and (c) healthy controls (n = 12), we assessed arterial wave velocity across the cardiac cycle, split into 10 stages, to capture variations in mechanical properties. Univariate analysis demonstrated a statistically significant inverse linear relationship between ADUV-derivedwave velocity and distensibility for the right CCA during the systolic phase (cardiac stages 3–5) and diastolic phase (cardiac stages 7–9) (−0.35 < ρ < −0.50, p < 0.02). The wave velocity showed associations with compliance in some of these phases. No significant correlations were observed between wave velocity and the stiffness index. Our findings provide insights into the clinical relevance of ADUV-derived wave velocity as a biomarker for arterial stiffness and its potential to complement or enhance traditional stiffness assessments.

World record speeds at different distances for men and women in different age categories are used to develop a model to predict running performance as a function of race distance, age, and sex. This empirical model quantifies the decline in running speed with distance and age in a way that provides insight into the aerobic and anaerobic contributions to running speed and may help with developing training strategies for different age groups at various distances.

Arterial stiffness predicts cardiovascular disease, the leading cause of death worldwide. Ultrasound elastography methods that measure wave velocity have promise for evaluating the stiffness of blood vessels in vivo. However, vessel geometry modulates wave velocity by inducing geometric dispersion. Here, we compare Young's modulus E estimates obtained using in vivo wave velocity measurements and techniques that either do or do not consider geometry to ex vivo reference E values from mechanical testing . An acoustic radiation force was applied to generate propagating waves in the right common carotid artery (N = 9) and external jugular vein (N = 10) of anesthetized pigs. Vessels were imaged with ultrafast ultrasound to measure wave motion. Group velocity cg was estimated from wave motion using a Radon transform. E was estimated from cg using a bulk media assumption which neglects geometry, as well as the Moens–Korteweg equation and a semi-analytical finite element model, which consider geometry. Pigs were euthanized and vessels were excised. Ring-shaped samples were extracted and tested in a uniaxial tension setup to obtain reference E values for comparison with E values obtained from wave-based techniques. Techniques considering geometry exhibited higher correlation with reference E values, underscoring the need to incorporate geometry for accurate vascular elastography assessments.

Severe impairment of oxygenation in critically ill patients is a major cause of morbidity and mortality, and can occur even with normal alveolar ventilation and cardiac output under conditions of decreased diffusing capacity or increased flow heterogeneity. A theoretical model of pulmonary oxygen uptake under resting conditions is used to simulate decreased diffusing capacity (DL) as well as increased heterogeneity (characterized by an increase in the coefficient of variation [CV] of pulmonary capillary blood flow), with the assumed normal value of CV based on observations of microvascular networks. Under resting conditions with nominal values of DL and CV, the model predicts an oxygen saturation (SO 2 ) of 97% (PO 2 = 94 mmHg). Simulating a 10‐fold reduction in DL leads to an SO 2 of 85% (PO 2 = 51 mmHg), whereas doubling the CV from its normal value leads to an SO 2 of 95% (PO 2 = 78 mmHg); both of these predictions suggest a high degree of reserve in the healthy resting lung. However, simulating these conditions simultaneously leads to a large reduction in SO 2 to 71% (PO 2 = 37 mmHg), exhausting the reserve capacity of the lung and demonstrating the detrimental synergistic effect of heterogeneity in the context of an attenuated diffusing capacity. These results imply that a combination of increased heterogeneity and decreased diffusing capacity can explain the severe impairment in pulmonary oxygen uptake and decreased saturations seen in critical illness. Support or Funding Information Supported by NIH grant HL070657.

AbstractOxygen transport from the lungs to peripheral tissue is dependent on the affinity of hemoglobin for oxygen. Recent experimental data have suggested that the maximum human capacity for oxygen uptake and utilization (V̇O2max) at sea level and altitude (~3000 m) is sensitive to alterations in hemoglobin‐oxygen affinity. However, the effect of such alterations on V̇O2max at extreme altitudes remains largely unknown due to the rarity of mutations affecting hemoglobin‐oxygen affinity. This work uses a mathematical model that couples pulmonary oxygen uptake with systemic oxygen utilization under conditions of high metabolic demand to investigate the effect of hemoglobin‐oxygen affinity on V̇O2max as a function of altitude. The model includes the effects of both diffusive and convective limitations on oxygen transport. Pulmonary oxygen uptake is calculated using a spatially‐distributed model that accounts for the effects of hematocrit and hemoglobin‐oxygen affinity. Systemic oxygen utilization is calculated assuming Michaelis–Menten kinetics. The pulmonary and systemic model components are solved iteratively to compute predicted arterial and venous oxygen levels. Values of V̇O2max are predicted for several values of hemoglobin‐oxygen affinity and hemoglobin concentration based on data from humans with hemoglobin mutations. The model predicts that increased hemoglobin‐oxygen affinity leads to increased V̇O2max at altitudes above ~4500 m.

Background: Hemoglobin, the primary oxygen-carrying protein in humans, provides the intermediate link between pulmonary oxygen uptake and tissue oxygen consumption. Oxygen transport is greatly influenced by the hemoglobin-oxygen affinity, which is commonly characterized by the metric P50 - defined as the oxygen tension at which 50% of hemoglobin is saturated. Humans with rare hemoglobin mutations causing a low P50 (high hemoglobin-oxygen affinity) have demonstrated remarkable preservation of exercise tolerance at high altitude conditions (~3,000m). However, the influence of a low P50 on V̇O2max at extreme altitudes (>5,500m) remains largely unexamined. To examine the dependence of V̇O2max on P50 and altitude, we developed a computational model of oxygen uptake and utilization. We hypothesized that a low P50 would result in a better maintained V̇O2max at extreme altitudes compared to conditions of normal P50 and high P50 (low hemoglobin-oxygen affinity). Methods: We created a model that couples pulmonary oxygen uptake with systemic oxygen utilization to estimate V̇O2max as a function of P50, hemoglobin concentration, and altitude. Fixed values for cardiac output and tissue oxygen demand for V̇O2max at sea level were assigned in accordance with experimental data. The pulmonary oxygen uptake model assumes a single blood compartment exposed to alveolar gas, from which the arterial oxygen tension may be estimated from venous input. Using the alveolar gas equation, we interpolated respiratory parameters from data obtained during human sojourn to the summit of Everest. The systemic oxygen utilization model uses arterial input parameters along with Michaelis-Menten kinetics to compute oxygen consumption. The Fick principle was used to determine the venous oxygen tension, which was assumed to approximate tissue oxygen tension. From these values, systemic oxygen extraction and V̇O2max were determined as a function of P50, hemoglobin concentration, and altitude. Results: We present the results for several cases of P50 (low, normal, and high) and hemoglobin concentrations as a function of altitude. For a low P50, the model demonstrated a greater arterial oxygen saturation, greater oxygen content, and lower systemic extraction at extreme altitudes compared to values determined for cases of normal and high P50. Additionally, a low P50 led to better maintenance of V̇O2max at ~8,850m (~38% decrease from sea-level V̇O2max) compared to values determined for normal P50 and high P50 (~53% and ~67% decrease from sea-level V̇O2max, respectively, P<0.05). Conclusion: This model demonstrates the importance of P50 in the determination of V̇O2max at various altitudes. At low altitudes, a low P50 does not confer an advantage in terms of oxygen utilization, likely due to diffusive oxygen limitations. However, at high and extreme altitudes, a greater convective oxygen transport associated with a low P50 likely outweighs impairments in oxygen diffusivity. This project was supported by the National Institutes of Health R-35-HL139854. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Shear Wave Elastography (SWE) involves estimating mechanical properties through inversion, i.e., matching measured and simulated propagation characteristics of shear waves in the tissue. The accuracy of the estimated properties depends significantly on the specific characteristics/responses that are being matched. These could range from simple group velocity to dispersion curves and to full-wave response (particle velocity measurements). Using specific applications of arterial, liver, and tumor elstography, we illustrate that effective SWE is performed by resorting to an inversion approach, or combination of inversion approaches, guided by the underlying physics. To this end, we present inversion approaches ranging from matching dispersion characteristics to matching full waveform responses and provide rationale for choosing the appropriate technique(s) depending on the problem at hand.

Arterial stiffness is a predictor of cardiovascular diseases, the leading causes of death worldwide. Ultrasound-based methods that measure arterial wave propagation have promise for evaluating local stiffness in vivo. However, geometric properties of arteries cause dispersion, invalidating typical assumptions underlying the relationship between shear modulus G and group velocity cg, which clinical implementations of ultrasound shear wave elastography do not consider. Here, we examine the dependence of these estimates on geometry and evaluate alternative approaches. Wave motion in the proximal wall of an artery after application of focused acoustic radiation force is simulated with a semi-analytical finite element (SAFE) model, and cg is estimated using a time-to-peak algorithm to determine G with several methods. First, the value of G a clinical scanner would report is calculated assuming a bulk medium. Second, a pulse wave velocity (PWV)-based G estimate is calculated by taking cg = PWV and applying the Moens–Korteweg equation. Third, we develop an interpolation-based method to provide a corrected G estimate using data generated by the SAFE model. Simulation results show severe geometry-dependent bias with the bulk method, which is partially ameliorated with the PWV method and substantially improved with the interpolation approach. Results are validated using arterial phantoms.

During hypoxic exposure, humans with high-affinity hemoglobin (and compensatory polycythemia) have blunted increases in heart rate compared with healthy humans with typical oxyhemoglobin dissociation curves. This response may be associated with altered autonomic control of heart rate. Our hypothesis-generating study aimed to investigate cardiac baroreflex sensitivity and heart rate variability among nine humans with high-affinity hemoglobin [6 females, O2 partial pressure at 50% [Formula: see text] (P50) = 16 ± 1 mmHg] compared with 12 humans with typical affinity hemoglobin (6 F, P50 = 26 ± 1 mmHg). Participants breathed normal room air for a 10-min baseline, followed by 20 min of isocapnic hypoxic exposure, designed to lower the arterial partial pressure O2 ([Formula: see text]) to ∼50 mmHg. Beat-by-beat heart rate and arterial blood pressure were recorded. Data were averaged in 5-min periods throughout the hypoxia exposure, beginning with the last 5 min of baseline in normoxia. Spontaneous cardiac baroreflex sensitivity and heart rate variability were determined using the sequence method and the time and frequency domain analyses, respectively. Cardiac baroreflex sensitivity was lower in humans with high-affinity hemoglobin than controls at baseline and during isocapnic hypoxic exposure (normoxia: 7 ± 4 vs. 16 ± 10 ms/mmHg, hypoxia minutes 15–20: 4 ± 3 vs. 14 ± 11 ms/mmHg; group effect: P = 0.02, high-affinity hemoglobin vs. control, respectively). Heart rate variability calculated in both the time (standard deviation of the N-N interval) and frequency (low frequency) domains was lower in humans with high-affinity hemoglobin than in controls (all P < 0.05). Our data suggest that humans with high-affinity hemoglobin may have attenuated cardiac autonomic function.