Attenuating intrathoracic pressure swings decreases cardiac output at different intensities of exercise.

Intrathoracic pressure (ITP) swings that permit spontaneous ventilation have physiological implications for the heart. We sought to determine the effect of respiration on cardiac output ( Q ̇ $\dot Q$ ) during semi-supine cycle exercise using a proportional assist ventilator to minimize ITP changes and lower the work of breathing (Wb ). Twenty-four participants (12 females) completed three exercise trials at 30%, 60% and 80% peak power (Wmax ) with unloaded (using a proportional assist ventilator, PAV) and spontaneous breathing. Intrathoracic and intraabdominal pressures were measured with balloon catheters placed in the oesophagus and stomach. Left ventricular (LV) volumes and Q ̇ $\dot Q$ were determined via echocardiography. Heart rate (HR) was measured with electrocardiogram and a customized metabolic cart measured oxygen uptake ( V ̇ O 2 ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}}}$ ). Oesophageal pressure swings decreased from spontaneous to PAV breathing by -2.8 ± 3.1, -4.9 ± 5.7 and -8.1 ± 7.7 cmH2 O at 30%, 60% and 80% Wmax , respectively (P = 0.01). However, the decreases in Wb were similar across exercise intensities (27 ± 42 vs. 35 ± 24 vs. 41 ± 22%, respectively, P = 0.156). During PAV breathing compared to spontaneous breathing, Q ̇ $\dot Q$ decreased by -1.0 ± 1.3 vs. -1.4 ± 1.4 vs. -1.5 ± 1.9 l min-1 (all P < 0.05) and stroke volume decreased during PAV breathing by -11 ± 12 vs. -9 ± 10 vs. -7 ± 11 ml from spontaneous breathing at 30%, 60% and 80% Wmax , respectively (all P < 0.05). HR was lower during PAV breathing by -5 ± 4 beats min-1 at 80% Wmax (P < 0.0001). Oxygen uptake decreased by 100 ml min-1 during PAV breathing compared to spontaneous breathing at 80% Wmax (P < 0.0001). Overall, attenuating ITPs mitigated LV preload and ejection, thereby suggesting that the ITPs associated with spontaneous respiration impact cardiac function during exercise. KEY POINTS: Pulmonary ventilation is accomplished by alterations in intrathoracic pressure (ITP), which have physiological implications on the heart and dynamically influence the loading parameters of the heart. Proportional assist ventilation was used to attenuate ITP changes and decrease the work of breathing during exercise to examine its effects on left ventricular (LV) function. Proportional assist ventilation with progressive exercise intensities (30%, 60% and 80% Wmax ) led to reductions in cardiac output at all intensities, primarily through reductions in stroke volume. Decreases in LV end-diastolic volume (30% and 60% Wmax ) and increases in LV end-systolic volume (80% Wmax ) were responsible for the reduction in stroke volume. The relationship between cardiac output and oxygen uptake is disrupted during respiratory muscle unloading.

The effect of proportional assist ventilation on the electrical activity of the human diaphragm during exercise.

NEW FINDINGS: What is the central question of this study? What is the effect of lowering the normally occurring work of breathing on the electrical activity and pressure generated by the diaphragm during submaximal exercise in healthy humans? What is the main finding and its importance? Ventilatory assist during exercise elicits a proportional lowering of both the work performed by the diaphragm and diaphragm electrical activity. These findings have implications for exercise training studies using proportional assist ventilation to reduce diaphragm work in patients with cardiopulmonary disease. ABSTRACT: We hypothesized that when a proportional assist ventilator (PAV) is applied in order to reduce the pressure generated by the diaphragm, there would be a corresponding reduction in electrical activity of the diaphragm. Healthy participants (five male and four female) completed an incremental cycle exercise test to exhaustion in order to calculate workloads for subsequent trials. On the experimental day, participants performed submaximal cycling, and three levels of assisted ventilation were applied (low, medium and high). Ventilatory parameters, pulmonary pressures and EMG of the diaphragm (EMGdi ) were obtained. To compare the PAV conditions with spontaneous breathing intervals, ANOVA procedures were used, and significant effects were evaluated with a Tukey-Kramer test. Significance was set at P < 0.05. The work of breathing was not different between the lowest level of unloading and spontaneous breathing (P = 0.151) but was significantly lower during medium (25%, P = 0.02) and high (36%, P < 0.001) levels of PAV. The pressure-time product of the diaphragm (PTPdi ) was lower across PAV unloading conditions (P < 0.05). The EMGdi was significantly lower in medium and high PAV conditions (P = 0.035 and P < 0.001, respectively). The mean reductions of EMGdi with PAV unloading were 14, 22 and 39%, respectively. The change in EMGdi for a given lowering of PTPdi with the PAV was significantly correlated (r = 0.61, P = 0.01). Ventilatory assist during exercise elicits a reduction in the electrical activity of the diaphragm, and there is a proportional lowering of the work of breathing. Our findings have implications for exercise training studies using assisted ventilation to reduce diaphragm work in patients with cardiopulmonary disease.

Characterization of the Lower Airways and Oral Microbiota in Healthy Young Persons in the Community.

Lower airway dysbiosis contributes to disease pathogenesis in respiratory diseases. However, little is known regarding the microbiota of lower airways or the oral cavity of healthy young persons. To address this gap, 25 healthy persons (24.3 ± 3.3 years; 52% females; no current smokers) underwent bronchoscopy during which bronchial brushing (BB) and bronchoalveolar lavage (BAL) fluid were collected. Prior to the procedure, an oral wash (OW) sample was also obtained. Microbiome analyses (16S rRNA locus) were performed (alpha- and beta-diversity, taxa annotations, and predicted functional metagenomic profiles) according to the airway compartment (BB, BAL, and OW). The greatest microbial richness was observed in OW and the lowest in BB (p < 0.001). Microbial communities differed significantly across compartments (p < 0.001), especially between BB and OW. Taxa analyses showed a significantly higher abundance of Firmicutes (BB: 32.7%; BAL: 31.4%) compared to OW (20.9%) (p < 0.001). Conversely, Proteobacteria predominated in OW (27.9%) as opposed to BB (7.0%) and BAL (12.5%) (p < 0.001), mostly due to a greater abundance of the bacteria in the Haemophilus genus in the OW (p < 0.001). The lower airway microbiota (BB and BAL) is significantly different from the OW microbiota in healthy young persons with respect to microbial diversity, taxa profiles, and predicted function.

Effects of 10 days of modest intermittent hypoxia on circulating measures of inflammation in healthy humans.

PURPOSE: Obstructive sleep apnea (OSA) is a common disease which is associated with elevated inflammatory markers and adhesion molecules, possibly due to nightly intermittent hypoxia (IH). The purpose of this study was to test the hypothesis that IH would increase systemic inflammatory markers in healthy human males. METHODS: Healthy, young male subjects (n = 9; 24 ± 2 years) were exposed to a single daily isocapnic hypoxia exposure (oxyhemoglobin saturation = 80%, 1 h/day) for 10 consecutive days. Serum granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1ß, interleukin-6, interleukin-8, leptin, monocyte chemotactic protein-1, vascular endothelial growth factor, intracellular adhesion molecule-1, and vascular cell adhesion molecule-1 were measured before and following the 10 days of IH using Luminex. RESULTS: Nine subjects completed the study (24 ± 2 years; 24 ± 2 kg/m(2)). The mean oxyhemoglobin saturation was 80.8 ± 1.6% during the hypoxia exposures. There was no significant change in any of the markers of inflammation (paired t test, P > 0.2 all cytokines). CONCLUSIONS: These findings suggest that (1) a more substantial or a different pattern of hypoxemia might be necessary to activate systemic inflammation, (2) the system may need to be primed before hypoxic exposure, or (3) increases in inflammatory markers in patients with OSA may be more related to other factors such as obesity or nocturnal arousal.

Therapeutic hypothermia attenuates physiologic, histologic, and metabolomic markers of injury in a porcine model of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a lung injury characterized by noncardiogenic pulmonary edema and hypoxic respiratory failure. The purpose of this study was to investigate the effects of therapeutic hypothermia on short-term experimental ARDS. Twenty adult female Yorkshire pigs were divided into four groups (n = 5 each): normothermic control (C), normothermic injured (I), hypothermic control (HC), and hypothermic injured (HI). Acute respiratory distress syndrome was induced experimentally via intrapulmonary injection of oleic acid. Target core temperature was achieved in the HI group within 1 h of injury induction. Cardiorespiratory, histologic, cytokine, and metabolomic data were collected on all animals prior to and following injury/sham. All data were collected for approximately 12 h from the beginning of the study until euthanasia. Therapeutic hypothermia reduced injury in the HI compared to the I group (histological injury score = 0.51 ± 0.18 vs. 0.76 ± 0.06; p = 0.02) with no change in gas exchange. All groups expressed distinct phenotypes, with a reduction in pro-inflammatory metabolites, an increase in anti-inflammatory metabolites, and a reduction in inflammatory cytokines observed in the HI group compared to the I group. Changes to respiratory system mechanics in the injured groups were due to increases in lung elastance (E) and resistance (R) (ΔE from pre-injury = 46 ± 14 cmH2 O L-1 , p < 0.0001; ΔR from pre-injury: 3 ± 2 cmH2 O L-1  s- , p = 0.30) rather than changes to the chest wall (ΔE from pre-injury: 0.7 ± 1.6 cmH2 O L-1 , p = 0.99; ΔR from pre-injury: 0.6 ± 0.1 cmH2 O L-1  s- , p = 0.01). Both control groups had no change in respiratory mechanics. In conclusion, therapeutic hypothermia can reduce markers of injury and inflammation associated with experimentally induced short-term ARDS.

Respiratory modulation of sympathetic vasomotor outflow during graded leg cycling.

Respiratory modulation of sympathetic vasomotor outflow to skeletal muscles (muscle sympathetic nerve activity; MSNA) occurs in resting humans. Specifically, MSNA is highest at end-expiration and lowest at end-inspiration during quiet, resting breathing. We tested the hypothesis that within-breath modulation of MSNA would be amplified during graded leg cycling. Thirteen (n = 3 females) healthy young (age: 25.2 ± 4.7 yr) individuals completed all testing. MSNA (right median nerve) was measured at rest (baseline) and during semirecumbent cycle exercise at 40%, 60%, and 80% of maximal workload (Wmax). MSNA burst frequency (BF) was 20.0 ± 4.0 bursts/min at baseline and was not different during exercise at 40%Wmax (21.3 ± 3.7 bursts/min; P = 0.292). Thereafter, MSNA BF increased significantly compared with baseline (60%Wmax: 31.6 ± 5.8 bursts/min; P < 0.001, 80%Wmax: 44.7 ± 5.3 bursts/min; P < 0.001). At baseline and all exercise intensities, MSNA BF was lowest at end-inspiration and greatest at mid-to-end expiration. The within-breath change in MSNA BF (ΔMSNA BF; end-expiration minus end-inspiration) gradually increased from baseline to 60%Wmax leg cycling, but no further increase appeared at 80%Wmax exercise. Our results indicate that within-breath modulation of MSNA is amplified from baseline to moderate intensity during dynamic exercise in young healthy individuals, and that no further potentiation occurs at higher exercise intensities. Our findings provide an important extension of our understanding of respiratory influences on sympathetic vasomotor control.NEW & NOTEWORTHY Within-breath modulation of sympathetic vasomotor outflow to skeletal muscle (muscle sympathetic nerve activity; MSNA) occurs in spontaneously breathing humans at rest. It is unknown if respiratory modulation persists during dynamic whole body exercise. We found that MSNA burst frequency was lowest at end-inspiration and highest at mid-to-end expiration during rest and graded leg cycling. Respiratory modulation of sympathetic vasomotor outflow remains intact and is amplified during dynamic whole body exercise.

Airway luminal area and the resistive work of breathing during exercise in healthy young females and males.

We examined the relationship between the work of breathing (Wb) during exercise and in vivo measures of airway size in healthy females and males. We hypothesized that sex differences in airway luminal area would explain the larger resistive Wb during exercise in females. Healthy participants (n = 11 females and n = 11 males; 19-30 yr) completed a cycle exercise test to exhaustion where Wb was assessed using an esophageal balloon catheter. On a separate day, each participant underwent a bronchoscopy procedure for optical coherence tomography measures of seven airways. In vivo measures of luminal area were made for the fourth to eighth airway generations. A composite index of airway size was calculated as the sum of the luminal area for each generation, and the total area was calculated based on Weibel's model. We found that index of airway size (males: 37.4 ± 6.3 mm2 vs. females: 27.5 ± 7.4 mm2) and airway area calculated based on Weibel's model (males: 2,274 ± 557 mm2 vs. females: 1,594 ± 389 mm2) were significantly larger in males (both P = 0.003). When minute ventilation was greater than ∼60 L·min-1, the resistive Wb was higher in females. At the highest equivalent flow achieved by all subjects, resistance to inspired flow was larger in females and significantly associated with two measures of airway size in all subjects: index of airway size (r = 0.524, P = 0.012) and Weibel area (r = 0.525, P = 0.012). Our findings suggest that innate sex differences in luminal area result in a greater resistive Wb during exercise in females compared with males.NEW & NOTEWORTHY We hypothesized that the higher resistive work of breathing in females compared with males during high-intensity exercise is due to smaller airways. In vivo measures of the fourth to eighth airway generations made using optical coherence tomography show that females tend to have smaller airway luminal areas of the fourth to sixth airway generations. Sex differences in airway luminal area result in a greater resistive work of breathing during exercise in females compared with males.

Does competitive swimming affect lung growth?

Whether the large lungs of swimmers result from intensive training or genetic endowment has been widely debated. Given that peak lung growth velocities occur during puberty, this study examined if competitive swimming during puberty affected lung growth. Eleven- to fourteen-year-old healthy female competitive swimmers and controls were assessed before (PRE) and after (POST) one swimming season (7.4 ± 0.5 months). Pulmonary function testing included lung volumes, spirometry, diffusion capacity (DL,CO ), and maximal inspiratory (PIMAX ) and expiratory (PEMAX ) pressures. Ventilatory constraints, including end-expiratory lung volume, expiratory flow limitation, and utilization of ventilatory capacity, were assessed during an incremental cycling test. Swimmers (n = 11) and controls (n = 10) were of similar age, size, and sexual maturity (P > 0.05). However, swimmers compared to controls had a greater total lung capacity (PRE 4.73 ± 0.73 vs. 3.93 ± 0.46, POST 5.08 ± 0.68 vs. 4.19 ± 0.64 L; P < 0.01), peak expiratory flow (PRE 6.48 ± 0.92 vs. 5.70 ± 0.86, POST 6.97 ± 0.84 vs. 6.00 ± 0.77 L·s-1 ; P = 0.03), and PEMAX (P < 0.001). Although DL,CO was greater in swimmers (P = 0.01), differences were attenuated when expressed relative to alveolar volume (PRE 5.14 ± 0.60 vs. 5.44 ± 0.44, POST 4.91 ± 0.56 vs. 5.16 ± 0.38 mL min-1  mmHg-1  L-1 ; P = 0.20). The groups achieved a similar maximal oxygen uptake (P = 0.32), and ventilatory constraints experienced were not different (P > 0.05). Changes over time were not different between groups (P > 0.05). At the initial measurement, pubertal female swimmers had greater lung size, expiratory flows, and indices of respiratory muscle strength, but similar ventilatory constraints while cycling. One competitive swimming season did not further accentuate this enhanced lung size and function or alter ventilatory mechanics, suggesting that competitive swimming during puberty did not affect lung growth.

Cardiovascular responses to vibrostimulation for sperm retrieval in men with spinal cord injury.

BACKGROUND/OBJECTIVE: Cardiovascular abnormalities and arrhythmias are common in individuals with spinal cord injury (SCI) who are undergoing vibrostimulation for sperm retrieval. The study aimed to examine cardiovascular control in men with SCI undergoing this procedure. METHODS: Individuals with chronic cervical (n=8; age: 33.1 +/- 1.9 years) and upper thoracic SCI (n=5; age: 35.2 +/- 2.9 years) volunteered for vibrostimulation, with continuous blood pressure (Finometer) and electrocardiographic monitoring. Patients were characterized further by sympathetic skin responses (SSR) to assess descending autonomic spinal pathways and American Spinal Injury Association (ASIA) scores to assess motor and sensory pathways. RESULTS: All but one subject with cervical SCI were ASIA A or B and were negative for SSR in the hands and feet. All subjects with upper thoracic SCI were ASIA A or B and were positive for SSR in the hands. Systolic blood pressure was lower in men with cervical injury at rest. Vibrostimulation induced an increase in systolic blood pressure >20 mmHg in all patients with cervical SCI (range = 125/65 - 280/152; median = 167/143 mmHg) and in 2 thoracic subjects (151/104 and 170/121 mmHg). During ejaculation, 6 cervical and 3 thoracic subjects developed arrhythmias (5 with bradycardia, 6 with premature atrial contractions, 4 with ventricular excitation, 1 with junctional rhythm, and 1 with heart block). CONCLUSION: The vibrostimulation procedure induced electrocardiographic abnormalities and autonomic dysreflexia in subjects with either cervical or high thoracic SCI.

Ventilation and respiratory mechanics.

During dynamic exercise, the healthy pulmonary system faces several major challenges, including decreases in mixed venous oxygen content and increases in mixed venous carbon dioxide. As such, the ventilatory demand is increased, while the rising cardiac output means that blood will have considerably less time in the pulmonary capillaries to accomplish gas exchange. Blood gas homeostasis must be accomplished by precise regulation of alveolar ventilation via medullary neural networks and sensory reflex mechanisms. It is equally important that cardiovascular and pulmonary system responses to exercise be precisely matched to the increase in metabolic requirements, and that the substantial gas transport needs of both respiratory and locomotor muscles be considered. Our article addresses each of these topics with emphasis on the healthy, young adult exercising in normoxia. We review recent evidence concerning how exercise hyperpnea influences sympathetic vasoconstrictor outflow and the effect this might have on the ability to perform muscular work. We also review sex-based differences in lung mechanics.

Child obesity and fitness levels among Kenyan and Canadian children from urban and rural environments: a KIDS-CAN Research Alliance Study.

OBJECTIVE: This study was designed to gather anthropometric and fitness-related data on Kenyan children living in urban (UKEN) and rural (RKEN) environments and to compare them with previous data collected on Canadian children in order to examine the potential nutrition-physical activity transition. METHODS: Height, weight, waist circumference, triceps skinfolds were directly measured on rural (RKEN) and urban Kenyan (UKEN) children (n = 179, 9-13 years) and compared with existing data from Canadian children living in urban and rural environments (n = 274, 9-13 years). Aerobic fitness was measured using the 20 m shuttle run, flexibility using the sit-and-reach test and isometric handgrip strength was assessed. RESULTS: None of the RKEN children were overweight or obese (OWO). However, 6.8% of UKEN boys and 16.7% of girls were OWO. The RKEN children had lower BMI, waist circumference, and triceps skinfolds than all other groups (UKEN, and Canadian: p < 0.05). UKEN children were leaner than Canadian children (p < 0.05). Male and female RKEN children had higher running speeds, and aerobic fitness than UKEN children (p < 0.001). Isometric strength was not different between Kenyan groups and was not different from urban living Canadian children. UKEN children were the least flexible group, and girls were more flexible than boys in all groups. CONCLUSIONS: Urban Kenyan children appear to be showing signs of the nutrition-physical activity transition, as judged by the anthropometric similarities to contemporary living Canadian children. Further support is provided by examining the difference in prevalence of overweight/obesity among UKEN compared with their RKEN counterparts and their lower aerobic fitness level.

Control of ventilation in humans following intermittent hypoxia.

Exposure to chronic or intermittent hypoxia produces alterations in the ventilatory response to hypoxia. These adaptations can differ depending on the severity of the hypoxic stimulus, its duration, its pattern, and the presence or absence of other chemical stimuli. As such, there are significant differences between the responses to intermittent versus continuous hypoxia. Intermittent hypoxia (IH) has been shown to elicit significant changes in the peripheral chemoresponse, but the functional implications of these changes for resting and exercise ventilation are not clear. We summarize the impact of IH on resting chemosensitivity and discuss the use of IH to better understand ventilatory control during exercise. We also suggest future directions for this relatively young field, including potential clinical applications of IH research.