Johnson, Bruce

Abstract The sections in this article are: Regulation of the Upper Airway During Exercise Anatomy and Physiology of the Upper Airway Contractile Properties and Endurance of Upper Airway Muscles Changes in Upper Airway Flow Resistance During Exercise Upper Airway Muscle Activities during Exercise Oronasal Distribution of Respiratory Airflow Effects of Exercise on Passive Respiratory Mechanics Elastic Properties Total Lung Capacity Expiratory Flow Rates, Vital Capacity, and Residual Volume Breathing Pattern During Exercise Mechanical Breathing Pattern Methods of Assessment of Respiratory Muscle Contraction Pattern of Respiratory Muscle Contraction Influence of Sensory Feedback on Breathing Pattern Influence of Respiratory Mechanics on Breathing Pattern Influence of Duration of Exercise on Breathing Pattern Influence of Mode of Exercise on Breathing Pattern Breathing Pattern during Recovery from Exercise Physiological Implications of Exercise Breathing Pattern Importance of Respiratory Load in Regulation of Exercise Hyperpnea Helium‐Oxygen Unloading Unloading with Pressure Assist Conclusion Locomotor‐Respiration Interdependence Entrainment—the Most Obvious Locomotor‐Respiratory Interaction How Does Entrainment Effect Ventilation? Is there Stronger Evidence to Support a Significant Biomechanical Effect of Locomotion on Respiration in Dogs? Are Biomechanical Effects Important in Entrainment in Humans? Locomotory: Respiratory Interactions, Independent of Entrainment Conclusion Respiratory Muscle Perfusion and Energetics Oxygen Cost of Hyperpnea Respiratory Muscle Blood Flow Exercise‐Induced Respiratory Muscle Fatigue Respiratory System Design Assessment of Diaphragm Fatigue in Animal Models Glycogen Depletion Fiber Type Recruitment Definition of Fatigue Task Failure vs. Objective Assessment of Fatigue Contractile Changes with Fatigue Predicting Respiratory Muscle Fatigue During Exercise Application of Resting Tests to Respiratory Muscle Function During Exercise Assessment of Respiratory Muscle Fatigue in Humans Volitional Tests Volitional Tests Applied to Exercise Nonvolitional Tests Bilateral Phrenic Nerve Stimulation ( BPNS ) Characteristics of Diaphragm Fatigue High‐ vs. Low‐Frequency Fatigue Sites and Mechanisms of Respiratory Muscle Fatigue Central Fatigue in Humans Neurotransmission Fatigue Bilateral Phrenic Nerve Stimulation Applied to Exercise Short‐Term Exercise Endurance Exercise Factors Contributing to the Decline in Twitch Pdi Following Exercise Role of Diaphragmatic Force Output in Fatigue Consequences of Exercise‐Induced Diaphragmatic Fatigue Fatigue vs. Task Failure Does Training of Respiratory Muscles Affect Exercise Performance? Altered Respiratory Muscle Recruitment with Fatigue Physical Training Effects on Respiratory Muscles Respiratory Muscle Morphology and Contractile Properties Whole‐Body Training: Effects on Rodent Respiratory Muscles Whole‐Body Exercise: Effects on Human Respiratory Muscle Performance Specific Respiratory Muscle Training Respiratory Sensation During Exertion Mechanisms of Respiratory Sensations during Exercise Methods of Assessing Respiratory Sensations Respiratory Movements An Urge to Breathe A Sense of Respiratory Effort Respiratory Sensation as a Respiratory Controller during Exercise Respiratory Sensation as a Limiting Factor during Exercise Conclusions Summary—Pulmonary System Limitations and Their Effects on Exercise Performance Absence of Pulmonary System Limitations in the Normally Fit Contrasting Adaptabilities: Demand vs. Capacity Alveolar Capillary Diffusion Surface of the Lung Ventilatory Limitations/Constraints Inadequate Alveolar Ventilation and Limitations Endurance Exercise Performance Special Circumstances Favoring Pulmonary Limitations to Exercise Performance in Health Hypoxia of High Altitudes Aging Effects on Pulmonary Limitations

Cardiogenic pulmonary edema is a life-threatening complication in patients with heart failure (HF) resulting from increased alveolar Cl- secretion and inhibition of alveolar epithelial Na+ channels (ENaC). Not all HF patients develop pulmonary edema, despite similar clinical characteristics, suggesting a genetic component to edema formation in response to cardiac failure. The ENaC are crucial for alveolar fluid clearance, with the alpha subunit demonstrating particular importance. We have previously found that genetic variation of the alpha subunit (SCNN1A) of ENaC, an alanine (A) to threonine (T) substitution, influences ion regulation during exercise and in response to albuterol. In the present study, we sought to determine the influence of the threonine variant (T663; AT/TT group) on lung fluid regulation in response to normobaric hypoxia, an environmental condition known to increase pulmonary capillary hydrostatic stress in healthy humans. Lung ion and fluid changes were assessed using exhaled Na+ (ENa+) and the lung diffusing capacity for carbon monoxide and nitric oxide (DLCO and DLNO, respectively) to determine alveolar-capillary membrane conductance (DM). 19 healthy subjects (n=8 vs. 11, %female=50 vs. 62%, age=27±1 vs. 28±2yrs., ht=171±3 vs. 173±2cm, wt=69±6 vs.72±3kg , BMI=23±1 vs.24±1kg/m2 , for AA and AT/TT, respectively) completed two overnight visits in a hypoxic tent simulating just over 5,400m. The visits were randomized to inhaled placebo (P) or inhaled amiloride (Aml, 1.5mg in 5ml normal saline, used to inhibit ENaC activity) with ENa+, DLCO, and DM assessed at baseline and following 12 hours of hypoxic exposure. There was an effect of genotype on the ENa+ response to hypoxia with placebo that was abolished with amiloride, but no effect of genotype on the diffusing capacity of the lung (Table). These results suggest that genetic variation of SCNN1A may influence ion regulation in the lung under conditions of elevated hydrostatic stress.

Medical compression garments are used to treat lymphatic disorders or conditions of poor venous return (e.g. orthostatic intolerance). Conventional compression garments, namely elastic compression sleeves and inflatable compression systems, may aid in relief of these conditions but are also limited in usability. Fixed levels of compression in elastic materials may induce challenges in donning/doffing, complicating patient compliance [1]. Compression levels in inflatable systems are customizable, but these garments are also bulky and require a tethered inflation source [2]. We are interested in developing easy-to-don/-doff compression garments using shape memory alloy (SMA) coil actuators that contract with heat from an applied current which can be wrapped around the body to apply compressive forces. More specifically, we use a spring coil formation as described by Holschuh et al. [3]. Further developed in the Wearable Technology Lab at the University of Minnesota, our current SMA compression garment (SMA-CG) design improves upon the work of Duvall et al. [4] presented in previous year’s (2017) Design of Medical Devices Conference, representing a year’s evolution in active compression garment design that integrate actuators made with SMA.

Current compression garments are often made from a spandex-type elastic material with static levels of compression and can become uncomfortable and difficult to don/doff [1]. This limits their usability, especially for unhealthy or aging populations. The only current alternative to elastic compression stockings are inflatable compression sleeves that are controllable, but highly immobile and must be tethered to an inflation source [2]. Neither design offers a solution that is simultaneously low profile, mobile, and controllable. Here we present the design and development of compression garments with embedded shape-changing materials that can produce controllable compression without the need for a bulky inflation system. This active materials approach enables dynamic control over the degree, timing and location of compression, and allows for graded, synchronized, pulsed, and peristaltic compression patterns, which provide the medical benefit of moving fluid in the body [2]. Such a design combines the best features of both elastic and inflatable compression garments: a slim, low-profile form factor that is easy to don/doff and provides dynamic control. Shape memory alloy (SMA) coil actuators, as described by Holschuh et al., [3] have the ability to apply compressive forces to the body when paired with passive textiles and wrapped circumferentially around the body. These actuators are engineered to contract when heated, creating controllable forces and displacements that are modulated through an applied current. SMA compression garments (SMA-CG) have important applications, from consumer uses to clinical interventions, including: augmenting venous return for conditions of orthostatic intolerance (e.g., postural orthostatic tachycardia syndrome (POTS)); cardiac rehabilitation in heart failure patients; lymphedema venous insufficiency; reducing deep vein thrombosis (DVT) risk; sports performance; and countermeasures for flight or space flight. While the potential uses for this technology are broad, the basic design is similar across many conditions. Key research areas include: 1) identifying and addressing design considerations relevant to prototype development of SMA-CG; 2) determining the compression thresholds needed to dynamically oppose orthostatic changes; and 3) evaluating the effectiveness of the prototypes for augmented venous return by synchronizing compression during cardiac diastole. Here, we focus on the first question: design of SMA-CG prototypes.

Altitude exposure has been associated with loss of appetite and weight loss in healthy humans; however, the endocrine factors that contribute to these changes remain unclear. Leptin and glucagon-like peptide-1 (GLP-1) are peptide hormones that contribute to the regulation of appetite. Leptin increases with hypoxia; however, the influence of hypoxia on GLP-1 has not been studied in animals or humans to date. We sought to determine the influence of normobaric hypoxia on plasma leptin and GLP-1 levels in 25 healthy humans. Subjects ingested a control meal during normoxia and after 17 h of exposure to normobaric hypoxia (fraction of inspired oxygen of 12.5%, simulating approximately 4100 m). Plasma leptin was assessed before the meal, and GLP-1 was assessed premeal, at 20 min postmeal, and at 40 min postmeal. We found that hypoxia caused a significant elevation in plasma leptin levels (normoxia, 4.9 ± 0.8 pg·mL–1; hypoxia, 7.7 ± 1.5 pg·mL–1; p < 0.05; range, –16% to 190%), no change in the average GLP-1 response to hypoxia, and only a small trend toward an increase in GLP-1 levels 40 min postmeal (fasting, 15.7 ± 0.9 vs 15.9 ± 0.7 pmol·L–1; 20 min postmeal, 21.7 ± 0.9 vs 21.8 ± 1.2 pmol·L–1; 40 min postmeal, 19.5 ± 1.2 vs. 21.0 ± 1.2 pmol·L–1 for normoxia and hypoxia, respectively; p > 0.05 normoxia vs hypoxia). There was a correlation between SaO2 and leptin after the 17 h exposure (r = 0.45; p < 0.05), but no relation between SaO2 and GLP-1. These data confirm that leptin increases with hypoxic exposure in humans. Further study is needed to determine the influence of hypoxia and altitude on GLP-1 levels.