Joyner, Michael J.

New Findings What is the central question of this study? How do locomotor muscle metabo‐ and mechanoreceptor expression compare in heart failure patients and controls? Do relationships exist between the protein expression and cardiopulmonary responses during exercise with locomotor muscle neural afferent feedback inhibition? What is the main finding and its importance? Heart failure patients exhibited greater protein expression of transient receptor potential vanilloid type 1 and cyclooxygenase‐2 than controls. These findings are important as they identify receptors that may underlie the augmented locomotor muscle neural afferent feedback in heart failure. AbstractHeart failure patients with reduced ejection fraction (HFrEF) exhibit abnormal locomotor group III/IV afferent feedback during exercise; however, the underlying mechanisms are unclear. Therefore, the purpose of this study was to determine (1) metabo‐ and mechanoreceptor expression in HFrEF and controls and (2) relationships between receptor expression and changes in cardiopulmonary responses with afferent inhibition. Ten controls and six HFrEF performed 5 min of cycling exercise at 65% peak workload with lumbar intrathecal fentanyl (FENT) or placebo (PLA). Arterial blood pressure and catecholamines were measured via radial artery catheter. A vastus lateralis muscle biopsy was performed to quantify cyclooxygenase‐2 (COX‐2), purinergic 2X3 (P2X3), transient receptor potential vanilloid type 1 (TRPV1), acid‐sensing ion channel 3 (ASIC3), Piezo 1 and Piezo 2 protein expression. TRPV1 and COX‐2 protein expression was greater in HFrEF than controls (both P < 0.04), while P2X3, ASIC3, and Piezo 1 and 2 were not different between groups (all P > 0.16). In all participants, COX‐2 protein expression was related to the percentage change in ventilation (r = −0.66) and mean arterial pressure (MAP) (r = −0.82) (both P < 0.01) with FENT (relative to PLA) during exercise. In controls, TRPV1 protein expression was related to the percentage change in systolic blood pressure (r = −0.77, P = 0.02) and MAP (r = −0.72, P = 0.03) with FENT (relative to PLA) during exercise. TRPV1 and COX‐2 protein levels are elevated in HFrEF compared to controls. These findings suggest that the elevated TRPV1 and COX‐2 expression may contribute to the exaggerated locomotor muscle afferent feedback during cycling exercise in HFrEF.

New Findings What is the central question of this study? Are sex difference in the central airways present in healthy paediatric patients? What is the main finding and its importance? In patients ≤12 years we found no sex differences in central airway luminal area. After 14 years, the males had significantly larger central airway luminal areas than the females. The sex differences were minimized, but preserved when correcting for height. Luminal area is the main determinant of airway resistance and our finding could help explain sex differences in pulmonary system limitations to exercise in paediatric patients. Abstract Cross‐sectional airway area is the main determinant of resistance to airflow in the respiratory system. In paediatric patients (<18 years), previous evidence for sex differences in cross‐sectional airway area was limited to patients with history of pulmonary disease or cadaveric studies with small numbers of subjects. These studies either only report tracheal data and do not include a range of ages or correct for height. Therefore, we sought to assess sex differences in airway luminal area utilizing paediatric patients of varying ages and no history of respiratory disease. Using three‐dimensional reconstructions from high‐resolution computed tomography scans, we retrospectively assessed the cross‐sectional airway area in healthy paediatric females ( n = 97) and males ( n = 128) over a range of ages (1–17 years). The areas of the trachea, left main bronchus, left upper lobe, left lower lobe, right main bronchus, intermediate bronchus and right upper lobe were measured at three discrete points by a blinded investigator. No differences between the sexes were noted in the cross‐sectional areas of the youngest (ages 1–12 years) patients ( P > 0.05). However, in patients ≥14 years the cross‐sectional areas were larger in the males compared to females in most airway sites. For instance, the cross‐sectional size of the trachea was 25% (218 ± 44 vs . 163 ± 24 mm 2 , P < 0.01) larger in males vs . females among ages 13–17 years. When accounting for height, these sex differences in airway areas were attenuated, but persisted. Our results indicate that sex differences in paediatric airway cross‐sectional area manifest after age ≥14 years and are independent of height.

Key points Theoretical models suggest there is no benefit of high affinity haemoglobin to preserve maximal oxygen uptake in acute hypoxia but the comparative biology literature has many examples of species that are evolutionarily adapted to hypoxia and have high affinity haemoglobin. We studied humans with high affinity haemoglobin and compensatory polycythaemia. These subjects performed maximal exercise tests in normoxia and hypoxia to determine how their altered haemoglobin affinity impacts hypoxic exercise tolerance. The high affinity haemoglobin participants demonstrated an attenuated decline in maximal aerobic capacity in acute hypoxia. Those with high affinity haemoglobin had no worsening of pulmonary gas exchange during hypoxic exercise but had greater lactate and lower pH than controls for all exercise bouts. High affinity haemoglobin and compensatory polycythaemia mitigated the decline in exercise performance in acute hypoxia through a higher arterial oxygen content and an unchanged pulmonary gas exchange. AbstractThe longstanding dogma is that humans exhibit an acute reduction in haemoglobin (Hb) binding affinity for oxygen that facilitates adaptation to moderate hypoxia. However, many animals have adapted to high altitude through enhanced Hb binding affinity for oxygen. The objective of the study was to determine whether high affinity haemoglobin (HAH) affects maximal and submaximal exercise capacity. To accomplish this, we recruited individuals (n = 11, n = 8 females) with HAH (P50 = 16 ± 1 mmHg), had them perform normoxic and acute hypoxic (15% inspired oxygen) maximal exercise tests, and then compared their results to matched controls (P50 = 26 ± 1, n = 14, n = 8 females). Cardiorespiratory and arterial blood gases were collected throughout both exercise tests. Despite no difference in end‐exercise arterial oxygen tension in hypoxia (59 ± 6 vs. 59 ± 9 mmHg for controls and HAH, respectively), the HAH subjects’ oxyhaemoglobin saturation () was ∼7% higher. Those with HAH had an attenuated decline in maximal oxygen uptake () (4 ± 5% vs. 12 ± %, p < 0.001) in hypoxia and the change in between trials was related to the change in (r = −0.75, p < 0.0001). Compared to normoxia, the controls’ alveolar‐to‐arterial oxygen gradient significantly increased during hypoxic exercise, whereas pulmonary gas exchange in HAH subjects was unchanged between the two exercise trials. However, arterial lactate was significantly higher and arterial pH significantly lower in the HAH subjects for both exercise trials. We conclude that HAH attenuates the decline in maximal aerobic capacity and preserves pulmonary gas exchange during acute hypoxic exercise. Our data support the comparative biology literature indicating that HAH is a positive adaptation to acute hypoxia.

The introduction of duplex Doppler ultrasound almost half a century ago signified a revolutionary advance in the ability to assess limb blood flow in humans. It is now widely used to assess blood flow under a variety of experimental conditions to study skeletal muscle resistance vessel function. Despite its pervasive adoption, there is substantial variability between studies in relation to experimental protocols, procedures for data analysis, and interpretation of findings. This guideline results from a collegial discussion among physiologists and pharmacologists, with the goal of providing general as well as specific recommendations regarding the conduct of human studies involving Doppler ultrasound-based measures of resistance vessel function in skeletal muscle. Indeed, the focus is on methods used to assess resistance vessel function and not upstream conduit artery function (i.e., macrovasculature), which has been expertly reviewed elsewhere. In particular, we address topics related to experimental design, data collection, and signal processing as well as review common procedures used to assess resistance vessel function, including postocclusive reactive hyperemia, passive limb movement, acute single limb exercise, and pharmacological interventions. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/guidelines-for-doppler-ultrasound-and-resistance-vessel-function/ .

Objectives: The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these 5 objectives: (1) describe sport related concussion (SRC) epidemiology; (2) classify prevention strategies; (3) define objective, diagnostic tests; (4) identify treatment; and (5) integrate science and clinical care into prioritized action plans and policy. Methods: Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. Results: To (1) establish a national and international hockey database for SRCs at all levels; (2) eliminate body checking in Bantam youth hockey games; (3) expand a behavior modification program (Fair Play) to all youth hockey levels; (4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues; (5) establish objective tests to diagnose concussion at point of care; and (6) mandate baseline testing to improve concussion diagnosis for all age groups. Conclusions: Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey.

Arterial baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of resistant hypertension. Previous studies suggested that the peripheral chemoreflex is tonically active in hypertensive patients and may inhibit baroreflex responses. We hypothesized that peripheral chemoreflex activation attenuates baroreflex efficacy evoked by electrical carotid sinus stimulation. We screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients with consistent acute depressor response were selected (7 men/4 women, age: 67±8 years, body mass index: 31.6±5.2 kg/m 2 , 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO 2 : 79.0±1.5%), and hyperoxia (40% end-tidal O 2 fraction) by measuring heart rate, blood pressure, ventilation, oxygen saturation, end-tidal CO 2 and O 2 fractions, and muscle sympathetic nerve activity. During normoxia, baroreflex activation reduced systolic blood pressure from 164±27 to 151±25 mm Hg (mean±SD, P <0.001), heart rate from 64±13 to 61±13 bpm ( P =0.002), and muscle sympathetic nerve activity from 42±12 to 36±12 bursts/min ( P =0.004). Hypoxia increased systolic blood pressure 8±12 mm Hg ( P =0.057), heart rate 10±6 bpm ( P <0.001), muscle sympathetic nerve activity 7±7 bursts/min ( P =0.031), and ventilation 10±7 L/min ( P =0.002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions: systolic blood pressure: −15±7 versus −14±8 mm Hg ( P =0.938), heart rate: −2±3 versus −2±2 bpm ( P =0.701), and muscle sympathetic nerve activity: −6±4 versus −4±3 bursts/min ( P =0.531). We conclude that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy in patients with resistant hypertension. These patients provided insight into human baroreflex-chemoreflex interactions that could not be gained otherwise.