Wiggins, Chad C

This study investigated the first multiomics data for association with tolerance to central hypovolemia in humans. Analyzing gene expression, proteins, and genetic variants in individuals with high and low tolerance to simulated hemorrhage, the findings show that severe blood loss causes widespread transcriptional changes, including the activation of innate immune system pathways and inhibition of gas transport processes. This research can help identify molecular factors that influence individuals’ tolerance levels for progressive blood loss.

AbstractInterstitial lung disease (ILD) encompasses pulmonary disorders characterized by chronic inflammation and fibrosis that disrupt pulmonary gas exchange. While ILD‐related changes in the lung parenchyma are well‐documented, less is known about how ILD affects luminal area within the large conducting airways. This retrospective, case–control study tested the hypothesis that patients with ILD would have greater large conducting airway luminal areas than healthy matched controls. Three‐dimensional reconstructions of computed tomography images were used to quantify airway luminal areas in patients with ILD (n = 82; 54% female) and healthy controls matched for age, sex, and height. Patients with ILD had 16%–22% greater airway luminal areas across all seven measured large conducting airways compared to controls (all p < 0.001). Among patients with ILD, males had 17%–34% greater height‐normalized airway luminal areas than females (all p < 0.05). These data provide evidence that ILD is associated with greater large conducting airway luminal area, even when matched for key demographic factors. Consistent with observations in health, males with ILD exhibited greater height‐normalized airway size than females. These findings offer new insight into airway remodeling in ILD and highlight potential sex differences in airway luminal area.

Intravenous dexmedetomidine infusion (selective α 2 -adrenergic receptor agonist) 1) reduced the firing probability and strength of baroreflex control over medium-sized sympathetic action potentials in muscle sympathetic nerve activity (MSNA) and 2) attenuated the transduction of MSNA bursts to changes in blood pressure (BP) by reducing the magnitude of BP responses and increasing the time to peak BP. These data suggest that neural and vascular α 2 -adrenergic mechanisms contribute to sympathetic baroreflex regulation of human BP.

There is a context-dependent trade-off in body size of elite runners, such that smaller body sizes are observed among longer distance runners. However, it is unclear whether this trade-off in body size is observed in other Olympic sports, such as cycling and swimming. To understand the association between body size and athletic competition, we examined metrics of body size from male and female Olympic athletes competing in swimming, running, and cycling. We collected standard anthropometrics (height, mass, body mass index (BMI), and body surface area) of elite male and female athletes competing in the London 2012 Summer Olympics from a public repository. Anthropometric data were compared between sexes (male and female); between sports (swimming, running, and cycling); and between distances within sports (shorter and longer distance). Males were taller ( P < 0.001), heavier ( P < 0.001), and had a larger BMI ( P < 0.001) compared to females. Relative to athletes competing in longer distance events, athletes competing in shorter distance were generally taller (running: P < 0.001, swimming: P ≤ 0.014) and heavier (running: P < 0.001, swimming: P = 0.002 (males) and P = 0.148 (females), cycling: P < 0.001) for both males and females. Height was not different between shorter and longer distance cyclists. There was a trade-off between body size and distance for each of the three Olympics sports, such that smaller athletes were observed in longer distance events. Although there were large sex-based differences in body size, similar trade-offs in size and event were observed for both males and females. These data suggest that there is an optimal combination of skeletal muscle mass and body size to optimize movement economy that is generally preserved across different modes of human locomotion.

The purpose of sympathetic neuronal discharge and the recruitment of neuronal subpopulations for human circulatory homeostasis remains unknown. This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. Across baseline and an intravenous dexmedetomidine infusion (α2-adrenergic agonist) sympathetic action potential (AP) frequency and total sympathetic AP clusters were associated with NPY bioavailability. This is the first study to report that sympathetic neuronal discharge and recruitment patterns regulate NPY bioavailability to support circulatory homeostasis in humans.

Three-dimensional reconstruction of airways has shown increased luminal area in patients with COVID-19 and post-acute sequelae of COVID-19 when compared with healthy controls. These findings suggest the role of large conducting airways in the pathogenesis of post-acute sequelae of COVID 19.

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.

Hypoxia exacerbates fatigue via central mechanisms after ischemic single-leg exercise. The greater fatigue observed during ischemic dynamic fatiguing exercise with hypoxia inspirate did not differ between the sexes. Hypoxia-induced central limitations are present in acute ischemic exercise and do not appear different in males and females.

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.

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.