Increase In Minute Ventilation Research Articles

Inspiratory muscle resistance combined with strength training: effects on aerobic capacity in artistic swimmers

ObjectiveThis study aimed to investigate the effects of combining inspiratory muscle resistance with strength training on lung function and aerobic capacity in artistic swimmers.MethodsThis research constitutes a placebo-controlled randomized trial, involving a five-week walking program conducted twice a week. Fourteen female artistic swimmers were randomly assigned to either the experimental group (TG group, n = 7) or the control group (CG group, n = 7). Both groups underwent the same strength training program. The TG group performed inspiratory muscle strengthening at 50% of maximum inspiratory pressure (MIP) during strength training, whereas the CG group engaged in strength training with 15% MIP inspiratory muscle training twice a week. Pre- and post-intervention assessments included an incremental stress test, pulmonary function test, inspiratory muscle strength test, and a specialized performance test.ResultsFollowing the 5-week intervention, within-group comparisons revealed that the inspiratory muscle strength index, vital capacity, and forced vital capacity significantly increased in both the CG and TG groups (P < 0.01). The TG group exhibited a significant increase in minute ventilation (P < 0.05), while the CG group showed a significant increase in tidal volume (P < 0.05). Additionally, the TG group demonstrated a significant improvement in running speed at the ventilation threshold and maximum oxygen uptake (P < 0.05), along with a significant increase in tidal volume (P < 0.01). Both the CG and TG groups showed significant increases in the scores for the 50-meter diving and 25-meter torpedo (P < 0.05). Between-group comparisons showed that the TG group experienced significant improvements in the inspiratory muscle strength index, minute ventilation, running speed corresponding to maximum oxygen uptake, and 25-meter torpedo performance (P < 0.05).ConclusionThe findings suggest that a 5-week program combining inspiratory muscle resistance with strength training can effectively enhance the aerobic exercise capacity of artistic swimmers. Moreover, high-intensity inspiratory muscle resistance combined with strength training can improve the muscle's ability to utilize oxygen during exercise. Trial RegistrationBeijing Research Institute of Sports Science (TKSLL202201); China Clinical Trial Registry, ChiCTR2300072833, 26/06/2023.

High flow nasal cannula and low level continuous positive airway pressure have different physiological effects during de novo acute hypoxemic respiratory failure

BackgroundLarge tidal volumes during de novo acute hypoxemic respiratory failure (AHRF) may promote patient self-inflicted lung injury. Tidal volume assessment under high flow nasal cannula (HFNC) is not routinely feasible at the bedside. Our objective was to determine whether tidal volume during low-level continuous positive airway pressure (CPAP) could predict tidal volume during HFNC and to compare the physiological effects of HFNC and low-level CPAP.MethodsProspective, single-center study including 29 de novo AHRF patients treated with HFNC (50 to 60 L.min− 1). Patients were monitored using electrical impedance tomography during HFNC then CPAP at 4 cmH2O. Tidal volume during HFNC was calculated based on tidal impedance variation. The ability of tidal volume under low-level CPAP to predict tidal volume under HFNC was explored using Bland-Altman analysis. CPAP and HFNC were compared in terms of tidal volume, minute ventilation, respiratory comfort, dyspnea, oxygenation, ventilation distribution, end-expiratory lung volume, thoraco-abdominal asynchrony and recruitment.ResultsUnder HFNC, patients had a tidal volume of 6.6 (5.9–8.7) mL.kg− 1 PBW. 20 (69%) patients exhibited a tidal volume between 4 and 8 mL.kg− 1 PBW, while in 5 (17%) patients it exceeded 9 mL.kg− 1 PBW. Tidal volume under CPAP was higher (9.4 (8.3–11) mL.kg− 1 PBW, p < 0.001). Tidal volumes under CPAP and under HFNC were modestly correlated (Spearman r = 0.50, p = 0.005). Bland-Altman analysis showed a bias of 2.4 mL.kg− 1, with limits of agreement ranging from − 1.1 mL.kg− 1to 5.9 mL.kg− 1. Nevertheless, a larger (> 11.5 mL.kg− 1 PBW ) tidal volume under low-level CPAP predicted a larger (> 9 mL.kg− 1 PBW ) tidal volume under HFNC with 80% sensitivity and 96% specificity. Low-level CPAP was associated with increased minute ventilation, end-expiratory lung volume, and oxygenation as compared to HFNC. It decreased signs of respiratory distress in the most severe patients but was associated with lower comfort compared to HFNC.ConclusionAmong ICU patients with de novo AHRF, tidal volume under HFNC was mostly protective. Tidal volume during CPAP at 4 cmH2O did not predict tidal volume during HFNC. Such low-level CPAP was associated with increased tidal volume, minute ventilation, end-expiratory volume, and oxygenation.Trial registrationClinicalTrials.gov ID NCT03919331. Registration date: 2019-03-26.

Malignant Hyperthermia: A Life-Threatening Condition in Patients Undergoing Surgical Intervention

Malignant hyperthermia (MH) is a rare, potentially fatal genetic disorder characterized by an unexplained elevation of expired carbon dioxide despite increased minute ventilation, muscle rigidity, and rhabdomyolysis, hyperthermia, tachycardia, acidosis, and hyperkalemia. It can be triggered by many pharmacological agents such as potent inhalation agents (halothane/ isoflurane/ sevoflurane/ desflurane), the depolarizing muscle relaxant (succinylcholine), and extreme physiological conditions such as vigorous exercise and working excessively in a hot and dry environment. Prompt and early recognition of the condition and rapid initiation of treatment measures are necessary to salvage the patient. Since MH is commonly encountered in the operating room or early postoperative period, anesthetists and surgeons need to keep themselves updated regarding the same. This review article aims to summarize our understanding of MH's pathophysiology, current diagnostics, management, and treatment strategies, along with a brief review of literature of published cases in Indian Subcontinent.

Cardiopulmonary exercise testing in long-term calcium channel blockers responders, does it normalize in the same way as pulmonary vascular resistance?

Abstract Background and aims Long-term calcium channel blockers (CCB) responders represent &amp;lt;10% of pulmonary arterial hypertension (PAH) patients and are known to have an excellent prognosis on high dose CCB. The few reports of lung histology of these patients suggest a predominant muscular thickening of the precapillary arterioles. Nevertheless, the classic intimal proliferation characteristic of PAH has also been reported, although to a lesser extent. Hence, we hypothesized that long-term CCB responders are likely to exhibit some degree of ventilatory inefficiency as a result of their impaired alveolo-capillary membrane. In this study, we aimed to evaluate the exercise performance of a contemporary cohort of long-term responders to CCB in terms of both exercise capacity and ventilatory efficiency, and whether there are differences depending on the haemodynamic severity. Methods We evaluated all long-term CCB responders with regular follow-up at our institution between 1996 to 2024 with at least one cardiopulmonary exercise test (CPET) and a right heart catheterization (RHC) within a three-year period, provided they had remained clinically stable without changes in pulmonary vasodilator treatment. Patients with additional PAH specific treatment were excluded. For data analysis purposes, the population was divided into 2 groups according to pulmonary vascular resistance (PVR). The cut-off point for PVR was set at ≥3. Results Twenty-four patients (91,6% female) with complete data were retrospectively enrolled. Baseline characteristics were as follows: median age 45.5 years (59-33) median mean pulmonary artery pressure of 26 mmHg (29-24) and median PVR of 3 WU (3-2.6). Regarding the whole cohort, peak oxygen consumption (pVO2) revealed mild impairment of functional capacity (mean pVO2: 1281 ± 245 ml/kg – 75 ± 15% of predicted). Ventilatory efficiency parameters were also mildy affected with low end-tidal carbon dioxide pressure at the anaerobic threshold (PETCO2@AT) (33.7±3.6mmHg), and increased minute ventilation (VE)/carbon dioxide output (VCO2) slope (33.5±4.5). The subgroup analysis depending on PVR showed no significant differences between groups in terms of pVO2 (1291.9 ±240 Vs. 1150 ±350 ml/kg, p:0.29 / 79%±16 vs 67%±12, p:0.8), VE/VCO2 slope (33 Vs. 34, p:0.21), or PETC02@AT (35 Vs. 33 mmHg, p:0.25). All CPET parameters by subgroups are displayed in Table 1. Conclusions Long-term CCB responders exhibit mildly reduced functional capacity. Moreover, they often fail to normalize the ventilatory efficiency parameters in most of the cases, even when PVR reaches close to normal values, suggesting persistent endothelial impairment.Results according to PVR

Suspected intracranial hypertension in COVID-19 patients with severe respiratory failure.

COVID-19 patients may exhibit neurological symptoms due to direct viral damage, systemic inflammatory syndrome, or treatment side effects. Mechanical ventilation in patients with severe respiratory failure often requires sedation and neuromuscular blockade, hindering thorough clinical examinations. This study aimed to investigate neurological involvement through clinical and noninvasive techniques and to detect signs of intracranial hypertension in these patients. We conducted a prospective observational study on mechanically ventilated COVID-19 adult patients admitted to our ICU, following standard of care protocols for ventilation and permissive hypercapnia. Data were collected at three time points: admission day (T1), day seven (T7), and day fourteen (T14). At each time point, patients underwent multimodal noninvasive neurological monitoring, including clinical examination, pupillary reactivity, transcranial color doppler of the middle cerebral artery (MCA), and optic nerve sheath diameter (ONSD) assessed via ultrasound (US). Head computer tomography (CT) was performed at T1 and T14. A limited subset of patients had a follow-up examination six months after ICU discharge. Seventy-nine patients were recruited; most were under deep sedation and neuromuscular blockade at T1. Pupillary size, symmetry, and reactivity were normal, as was the MCA mean velocity. However, ONSD, assessed by both US and CT, appeared enlarged, suggesting raised intracranial pressure (ICP). In a subgroup of 12 patients, increased minute ventilation was associated with a significant decrease in US-ONSD, corresponding to a drop in paCO2. At follow-up, twelve patients showed no long-term neurological sequelae, and US-ONSD was decreased in all of them. In this cohort, enlarged ONSD was detected during non-invasive neurological monitoring, suggesting a raised ICP, with hypercapnia playing a prominent role. Further studies are needed to explore ONSD behavior in other samples of mechanically ventilated, hypercapnic patients.

Effects of sodium bicarbonate ingestion on ventilatory and cerebrovascular responses in resting heated humans.

Hyperthermia stimulates ventilation in humans. This hyperthermia-induced hyperventilation may be mediated by the activation of peripheral chemoreceptors implicated in the regulation of respiration in reaction to various chemical stimuli, including reductions in arterial pH. Here, we investigated the hypothesis that during passive heating at rest, the increases in arterial pH achieved with sodium bicarbonate ingestion, which could attenuate peripheral chemoreceptors activity, mitigate hyperthermia-induced hyperventilation. We also assessed that the effect of sodium bicarbonate ingestion on cerebral blood flow responses, which are associated with hyperthermia-induced hyperventilation. Twelve healthy men ingested a sodium bicarbonate (0.3 g/kg body weight) or sodium chloride (0.208 g/kg). One hundred minutes after the ingestion, the participants were passively heated using hot-water immersion (42°C) combined with a water-perfused suit. Increases in esophageal temperature (an index of core temperature) and minute ventilation (VE) during the heating were similar in the two trials. Moreover, when VE is expressed as a function of esophageal temperature, there were no between-trial differences in the core temperature threshold for hyperventilation (37.9 ± 0.3 vs. 38.0 ± 0.4°C, P = 0.338), and sensitivity of hyperthermia-induced hyperventilation as assessed by the slope of the core temperature-VE relation (13.7 ± 14.9 vs. 15.8 ± 15.6 L/min/°C, P = 0.748). Furthermore, middle cerebral artery mean blood velocity (an index of cerebral blood flow) decreased similarly with heating duration in both trials. These results suggest that sodium bicarbonate ingestion does not mitigate hyperthermia-induced hyperventilation and the reductions in cerebral blood flow index in resting heated humans.

Ageing-related modification of sleep and breathing in orexin-knockout narcoleptic mice.

Narcolepsy type-1 (NT1) is a lifelong sleep disease, characterised by impairment of the orexinergic system, with a typical onset during adolescence and young adulthood. Since the wake-sleep cycle physiologically changes with ageing, this study aims to compare sleep patterns between orexin-knockout (KO) and wild type (WT) control mice at different ages. Four groups of age-matched female KO and WT mice (16 weeks of age: 8 KO-YO and 9 WT-YO mice; 87 weeks of age: 13 KO-OLD and 12 WT-OLD mice) were implanted with electrodes for discriminating wakefulness, rapid-eye-movement sleep (REMS), and non-REMS (NREMS). Mice were recorded for 48 h in their home cages and for 7 more hours into a plethysmographic chamber to characterise their sleep-breathing pattern. Regardless of orexin deficiency, OLD mice spent less time awake and had fragmentation of this behavioural state showing more bouts of shorter length than YO mice. OLD mice also had more NREMS bouts and less frequent NREMS apneas than YO mice. Regardless of age, KO mice showed cataplexy-like episodes and shorter REMS latency than WT controls and had a faster breathing rate and an increased minute ventilation during REMS. KO mice also had more wakefulness, NREMS and REMS bouts, and a shorter mean length of wakefulness bouts than WT controls. Our experiment indicated that the lack of orexins as well as ageing importantly modulate the sleep and breathing phenotype in mice. The narcoleptic phenotype caused by orexin deficiency in female mice was substantially preserved with ageing.

Changes in preBötzinger Complex neuron discharge associated with changes in PCO2 in decerebrate rabbits

Background: Maskrey and Nicol reported a strong increase in minute ventilation with increase in PCO2 (J Physiol 1980, 301: 49-58). We investigated a) whether there was a ceiling to this effect at high CO2 levels and b) whether the change in ventilation was associated with specific changes in respiratory neurons in the preBötzinger complex (preBC). Methods: The study was approved by the local Animal Care Committee and conformed to NIH standards. Adult New Zealand White rabbits (3-4 kg) were anesthetized, tracheotomized, ventilated, decerebrated and vagotomized. Phrenic nerve activity was recorded from the C5 rootlet, time averaged and used to calculate inspiratory (TI) and expiratory durations (TE) and peak phrenic activity (PPA). PPA was normalized to the value at PCO2 50mmHg. Individual neurons were recorded in the functionally identified preBC using multichannel electrodes at increasing CO2 levels. Statistical analysis used the Wilcoxon signed-rank test to determine changes in respiratory parameters between CO2 levels and Friedman RM-ANOVA to determine changes in neuronal discharge frequency (Fn). A generalized linear mixed model was used to determine associations between CO2-dependent changes in TI, TE, PPA, and changes in Fn for different neuron types. p&lt;0.05 indicated a significant difference. Results: In 34 animals, the increase in minute ventilation with increasing PCO2 was due mostly to the change in PPA. The increase in respiratory rate was due mostly to a decrease in TE. There was little increase in respiratory output at PCO2 &gt; 50 mmHg. In 209 neurons, increasing PCO2 increased Fn in inspiratory augmenting (I aug, n= 70, p&lt;0.0001 for CO2 30 vs 40 and 40 vs 50mmHg), I parabolic (I para, n=43, p&lt;0.0001 for CO2 40 vs 50 mmHg), pre-inspiratory (pre-I, n=35, p&lt;0.01 for CO2 30 vs 40 mmHg), and expiratory decrementing (E dec, n=44, p&lt;0.01 for CO2 40 vs 50 mmHg) neurons, but not in I dec (n=8) and non-respiratory modulated (NRM, n=9) neurons. The strongest correlation was found between the changes in phase timing and PPA and Fn in I aug and pre-I neurons. Conclusion: We found a ceiling effect to the increase in respiratory output at PCO2 levels &gt; 50 mmHg. Inspiratory preBC neuron subtypes were more affected by the changes in PCO2. NIH R01HL159546. This is the full abstract presented at the American Physiology Summit 2024 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.

During exposure to 3%, 5%, and 7% CO2, both Behaviorally Inhibited and Non-Behaviorally Inhibited individuals increased minute ventilation through different mechanisms

Behavioral inhibition (BI) is a temperament associated with increased vulnerability to stress compared to their non-behaviorally inhibited (NBI) counterparts. Previous studies have demonstrated that BI individuals have a higher stress response than NBI individuals, suggesting that BI individuals have significantly less parasympathetic nervous system output at rest. However, this study only compared room air to 7% carbon dioxide (CO2) concentrations. The difference in the sympathetic nervous system activation between BI and NBI individuals under constant increasing stress is still unknown. Our current study tested the hypothesis that BI individuals will have an increased stress response as the inhaled CO2 concentration increases. In humans, we tested the effect of increasing CO2 concentrations on tidal volume, breathing rate, heart rate, and blood pressure. BI individuals were identified through self-reported questionnaires, such as The Adult Measure of Behavioral Inhibition (AMBI). A 15-minute control period of room air breathing was completed followed by 5 minutes each of 3% and 5% inspired CO2, and 3 minutes of 7% inspired CO2. Preliminary results indicate that BI individuals breathe differently at a physiological level and differ in their stress response. Thank you to Carthage College's Student Travel Grant as well as the Neuroscience and Biology department for supporting this research. This is the full abstract presented at the American Physiology Summit 2024 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.

SubSol-HIe is an AMPK-dependent hypoxia-responsive subnucleus of the nucleus tractus solitarius that coordinates the hypoxic ventilatory response and protects against apnoea in mice

Functional magnetic resonance imaging (fMRI) suggests that the hypoxic ventilatory response is facilitated by the AMP-activated protein kinase (AMPK), not at the carotid bodies, but within a subnucleus (Bregma -7.5 to -7.1 mm) of the nucleus tractus solitarius that exhibits right-sided bilateral asymmetry. Here, we map this subnucleus using cFos expression as a surrogate for neuronal activation and mice in which the genes encoding the AMPK-α1 (Prkaa1) and AMPK-α2 (Prkaa2) catalytic subunits were deleted in catecholaminergic cells by Cre expression via the tyrosine hydroxylase promoter. Comparative analysis of brainstem sections, relative to controls, revealed that AMPK-α1/α2 deletion inhibited, with right-sided bilateral asymmetry, cFos expression in and thus activation of a neuronal cluster that partially spanned three interconnected anatomical nuclei adjacent to the area postrema: SolDL (Bregma -7.44 mm to -7.48 mm), SolDM (Bregma -7.44 mm to -7.48 mm) and SubP (Bregma -7.48 mm to -7.56 mm). This approximates the volume identified by fMRI. Moreover, these nuclei are known to be in receipt of carotid body afferent inputs, and catecholaminergic neurons of SubP and SolDL innervate aspects of the ventrolateral medulla responsible for respiratory rhythmogenesis. Accordingly, AMPK-α1/α2 deletion attenuated hypoxia-evoked increases in minute ventilation (normalised to metabolism), reductions in expiration time, and increases sigh frequency, but increased apnoea frequency during hypoxia. The metabolic response to hypoxia in AMPK-α1/α2 knockout mice and the brainstem and spinal cord catecholamine levels were equivalent to controls. We conclude that within the brainstem an AMPK-dependent, hypoxia-responsive subnucleus partially spans SubP, SolDM and SolDL, namely SubSol-HIe, and is critical to coordination of active expiration, the hypoxic ventilatory response and defence against apnoea.

High-intensity interval training improves respiratory and cardiovascular adjustments before and after initiation of exercise.

Purpose: High-intensity interval training (HIIT) may induce training-specific physiological adaptations such as improved respiratory and cardiovascular adjustments before and after the onset of high-intensity exercise, leading to improved exercise performance during high-intensity exercise. The present study investigated the effects of HIIT on time-dependent cardiorespiratory adjustment during maximal exercise and before and after initiation of high-intensity exercise, as well as on maximal exercise performance. Methods: 21 healthy male college students were randomly assigned to HIIT group (n = 11) or control group (n = 10). HIIT group performed training on a cycle ergometer once a week for 8 weeks. The training consisted of three bouts of exercise at 95% maximal work rate (WRmax) until exhaustion. Before and after the HIIT program, dynamic cardiorespiratory function was investigated by ramp and step exercise tests, and HIIT-induced cardiac morphological changes were assessed using echocardiography. Results: HIIT significantly improved not only maximal oxygen uptake and minute ventilation, but also maximal heart rate (HR), systolic blood pressure (SBP), and time to exhaustion in both exercise tests (p < 0.05). Time-dependent increases in minute ventilation (VE) and HR before and at the start of exercise were significantly enhanced after HIIT. During high-intensity exercise, there was a strong correlation between percent change (from before to after HIIT program) in time to exhaustion and percent change in HRmax (r = 0.932, p < 0.001). Furthermore, HIIT-induced cardiac morphological changes such as ventricular wall hypertrophy was observed (p < 0.001). Conclusion: We have demonstrated that HIIT at 95% WRmax induces training-specific adaptations such as improved cardiorespiratory adjustments, not only during maximal exercise but also before and after the onset of high-intensity exercise, improvement of exercise performance mainly associated with circulatory systems.

Sports Bra Restriction on Respiratory Mechanics during Exercise.

We set out to understand how underband tightness or pressure of a sports bra relates to respiratory function and the mechanical work of breathing ( during exercise. Our secondary purpose was to quantify the effects of underband pressure on O 2 during submaximal running. Nine highly trained female runners with normal pulmonary function completed maximal and submaximal running in three levels of underband restriction: loose, self-selected, and tight. During maximal exercise, we observed a significantly greater during the tight condition (350 ± 78 J·min -1 ) compared with the loose condition (301 ± 78 J·min -1 ; P < 0.05), and a 5% increase in minute ventilation ( ) during the tight condition compared with the loose condition ( P < 0.05). The pattern of breathing also differed between the two conditions; the greater maximal during the tight condition was achieved by a higher breathing frequency (57 ± 6 vs. 52 ± 7 breaths·min -1 ; P < 0.05), despite tidal volume being significantly lower in the tight condition compared with the loose condition (1.97 ± 0.20 vs. 2.05 ± 0.23 L; P < 0.05). During steady-state submaximal running, O 2 increased 1.3 ± 1.1% (range: -0.3 to 3.2%, P < 0.05) in the tight condition compared with the loose condition. Respiratory function may become compromised by the pressure exerted by the underband of a sports bra when women self-select their bra size. In the current study, loosening the underband pressure resulted in a decreased work of breathing, changed the ventilatory breathing pattern to deeper, less frequent breaths, and decreased submaximal oxygen uptake (improved running economy). Our findings suggest sports bra underbands can impair breathing mechanics during exercise and influence whole-body metabolic rate.

Effects on mechanical power of different devices used for inhaled sedation in a bench model of protective ventilation in ICU

BackgroundInhaled sedation during invasive mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) has received increasing attention. However, inhaled sedation devices increase dead-space ventilation and an undesirable effect is the increase in minute ventilation needed to maintain CO2 removal. A consequence of raising minute ventilation is an increase in mechanical power (MP) that can promote lung injury. However, the effect of inhaled sedation devices on MP remains unknown.MethodsWe conducted a bench study to assess and compare the effects of three devices delivering inhaled sevoflurane currently available in ICU (AnaConDa-50 mL (ANA-50), AnaConDa-100 mL (ANA-100), and MIRUS) on MP by using a test lung model set with three compliances (20, 40, and 60 mL/cmH2O). We simulated lung-protective ventilation using a low tidal volume and two levels of positive end-expiratory pressure (5 and 15 cmH2O) under ambient temperature and dry conditions. Following the insertion of the devices, either the respiratory rate or tidal volume was increased in 15%-steps until end-tidal CO2 (EtCO2) returned to the baseline value. MP was calculated at baseline and after EtCO2 correction using a simplified equation.ResultsFollowing device insertion, the EtCO2 increase was significantly greater with MIRUS (+ 78 ± 13%) and ANA-100 (+ 100 ± 11%) than with ANA-50 (+ 49 ± 7%). After normalizing EtCO2 by adjusting minute ventilation, MP significantly increased by more than 50% with all inhaled sedation devices compared to controls. The lowest increase in MP was observed with ANA-50 (p < 0.05 versus ANA-100 and MIRUS). The Costa index, another parameter assessing the mechanical energy delivered to the lungs, calculated as driving pressure × 4 + respiratory rate, significantly increased by more than 20% in all experimental conditions. Additional experiments performed under body temperature, ambient pressure, and gas saturated with water vapor conditions, confirmed the main results with an increase in MP > 50% with all devices after normalizing EtCO2 by adjusting minute ventilation.ConclusionInhaled sedation devices substantially increased MP in this bench model of protective ventilation, which might limit their benefits in ARDS.

Load carriage physiology in normoxia and hypoxia

PurposeTo determine the effects of load carriage in normoxia and normobaric hypoxia on ventilatory responses, hemodynamics, tissue oxygenation, and metabolism.MethodsHealthy males (n = 12) completed 3 randomly ordered baseline graded exercise tests in the following conditions: (1) unloaded normoxic (U: FIO2 = 20.93%), (2) loaded (~ 30 kg) normoxic (LN), and (3) loaded hypoxic simulating ~ 3650 m (LH: FIO2 = ~ 13%). Thereafter, experimental exercise trials were completed in quasi-randomized order (i.e., U completed first) consisting of 3 × 10 min of walking (separated by 5 min seated rest) with stages matched with the U condition (in ascending order) for relative intensity, absolute oxygen consumption ([VO2]; 1.7 L min−1), and walking speed (1.45 ± 0.15 m s−1).ResultsLoad carriage increased perceived exertion and reduced VO2max (LN: − 7%; LH: − 32%; p < 0.05). At matched VO2, stroke volume and tidal volume were reduced and maintained with LN and LH vs. U, respectively (p < 0.05). Increases in cardiac output and minute ventilation at matched VO2 (with LH) and speed (with LN and LH), were primarily accomplished via increases in heart rate and breathing frequency (p < 0.05). Cerebral oxygenated hemoglobin (O2HHb) was increased at all intensities with LN, but deoxygenated hemoglobin and total hemoglobin were increased with LH (p < 0.05). Muscle oxygen kinetics and substrate utilization were similar between LN and U, but LH increased CHO dependence and reduced muscle O2HHb at matched speed (p < 0.05).ConclusionLoad carriage reduces cardiorespiratory efficiency and increases physiological strain, particularly in hypoxic environments. Potential load carriage-induced alterations in cerebral blood flow may increase the risk for altitude illnesses and requires further study.

Erythrocytic metabolism of ATLX-0199: An agent that increases minute ventilation

Both L- and D-isomers of S-nitrosocysteine (CSNO) can bind to the intracellular domain of voltage-gated potassium channels in vitro. CSNO binding inhibits these channels in the carotid body, leading to increased minute ventilation in vivo. However, only the l-isomer is active in vivo because it requires the l-amino acid transporter (LAT) for transmembrane transport. In rodents and dogs, the esterified D-CSNO precursor—d-cystine dimethyl ester (ATLX-0199)—overcomes opioid- and benzodiazepine-induced respiratory depression while maintaining analgesia. Although ATLX-0199 can enter cells independently of LAT because it is an ester, its stability in plasma is limited by the presence of esterases. Here, we hypothesized that the drug could be sequestered in erythrocytes to avoid de-esterification in circulation. We developed a liquid chromatography-mass spectrometry method for detecting ATLX-0199 and characterized a new metabolite, S-nitroso-d-cysteine monomethyl ester (DNOCE), which is also a D-CSNO precursor. We found that both ATLX-0199 and DNOCE readily enter erythrocytes and neurons and remain stable over 20 min; thus ATLX-0199 can enter cells where the ester is stable, but the thiol is reduced. Depending on hemoglobin conformation, the reduced ester can be S-nitrosylated and enter carotid body neurons, where it then increases minute ventilation. These data may help explain the paradox that ATLX-0199, a dimethyl ester, can avoid de-esterification in plasma and exert its effects at the level of the carotid body.

Quantifying ventilation by X-ray velocimetry in healthy adults

RationaleX-ray velocimetry (XV) has been utilized in preclinical models to assess lung motion and regional ventilation, though no studies have compared XV-derived physiologic parameters to measures derived through conventional means.ObjectivesTo assess agreement between XV-analysis of fluoroscopic lung images and pitot tube flowmeter measures of ventilation.MethodsXV- and pitot tube-derived ventilatory parameters were compared during tidal breathing and with bilevel-assisted breathing. Levels of agreement were assessed using the Bland-Altman analysis. Mixed models were used to characterize the association between XV- and pitot tube-derived values and optimize XV-derived values for higher ventilatory volumes.Measurements and main resultsTwenty-four healthy volunteers were assessed during tidal breathing and 11 were reassessed with increased minute ventilation with bilevel-assisted breathing. No clinically significant differences were observed between the two methods for respiratory rate (average Δ: 0.58; 95% limits of agreement: -1.55, 2.71) or duty cycle (average Δ: 0.02; 95% limits of agreement: 0.01, 0.03). Tidal volumes and flow rates measured using XV were lower than those measured using the pitot tube flowmeter, particularly at the higher volume ranges with bilevel-assisted breathing. Under these conditions, a mixed-model based adjustment was applied to the XV-derived values of tidal volume and flow rate to obtain closer agreement with the pitot tube-derived values.ConclusionRadiographically obtained measures of ventilation with XV demonstrate a high degree of correlation with parameters of ventilation. If the accuracy of XV were also confirmed for assessing the regional distribution of ventilation, it would provide information that goes beyond the scope of conventional pulmonary function tests or static radiographic assessments.

Pilot Project: Heart Chargers-A Successful Model for a Home-Based Physical Activity Program Utilizing Telemedicine for Fontan Patients.

Fontan patients have decreased exercise capacity which further declines throughout adolescence. A positive exercise capacity trajectory in children predicts better adult Fontan outcomes. Hospital-based physical activity programs improve exercise capacity and attenuate the age-expected decline in Fontan patients. The purpose of this project was to investigate the feasibility and safety of a partially reimbursable 12-month, home-based, individualized physical activity program (Heart Chargers) for Fontan patients utilizing telemedicine. The Heart Chargers team included a cardiologist, nurse coordinator, and exercise physiologists. Eligible participants with a Fontan completed a baseline cardiopulmonary exercise test (CPET) and consented to participate in Heart Chargers, a 12-month home-based exercise prescription. The individualized exercise prescription focused on skeletal and respiratory muscle strength training and aerobic activities. Participants received a Garmin© device to monitor adherence. Telephone check-ins ranged from weekly to monthly as participants gained independence. Pre- and post-program CPET and informal surveys of physical activity self-efficacy were completed. Nine participants have completed the Heart Chargers program. There was no pre-postdifference in maximal or submaximal oxygen consumption (VO2), peak heart rate, or oxygen saturation. There was a significant pre-post increase in systolic blood pressure (p-value 0.004) and minute ventilation (p-value 0.012) at peak exercise. Per subjective report, exercise-related self-efficacy increased after program completion. There were no adverse events. At present, 7 participants remain actively enrolled in the program. Heart Chargers, a novel, home-based, partially reimbursable, 12-month individualized exercise program using telemedicine was successfully implemented in Fontan patients with no adverse events. The lack of decline in exercise capacity for participants is encouraging.

Balanced volatile sedation with isoflurane in critically ill patients with aneurysmal subarachnoid hemorrhage - a retrospective observational study.

In patients with severe aneurysmal subarachnoid hemorrhage (SAH) deep sedation is often used early in the course of the disease in order to control brain edema formation and thus intracranial hypertension. However, some patients do not reach an adequate sedation depth despite high doses of common intravenous sedatives. Balanced sedation protocols incorporating low-dose volatile isoflurane administration might improve insufficient sedation depth in these patients. We retrospectively analyzed ICU patients with severe aneurysmal SAH who received isoflurane in addition to intravenous anesthetics in order to improve insufficient sedation depth. Routinely recorded data from neuromonitoring, laboratory and hemodynamic parameters were compared before and up to 6 days after initiation of isoflurane. Sedation depth measured using the bispectral index improved in thirty-six SAH patients (-15.16; p = 0.005) who received additional isoflurane for a mean period of 9.73 ± 7.56 days. Initiation of isoflurane sedation caused a decline in mean arterial pressure (-4.67 mmHg; p = 0.014) and cerebral perfusion pressure (-4.21 mmHg; p = 0.013) which had to be balanced by increased doses of vasopressors. Patients required increased minute ventilation in order to adjust for the increase in PaCO2 (+2.90 mmHg; p < 0.001). We did not detect significant increases in mean intracranial pressure. However, isoflurane therapy had to be terminated prematurely in 25% of the patients after a median of 30 h due to episodes of intracranial hypertension or refractory hypercapnia. A balanced sedation protocol including isoflurane is feasible for SAH patients experiencing inadequately shallow sedation. However, therapy should be restricted to patients without impaired lung function, hemodynamic instability and impending intracranial hypertension.

Chronic pulmonary fibrosis alters the functioning of the respiratory neural network.

Some patients with idiopathic pulmonary fibrosis present impaired ventilatory variables characterised by low forced vital capacity values associated with an increase in respiratory rate and a decrease in tidal volume which could be related to the increased pulmonary stiffness. The lung stiffness observed in pulmonary fibrosis may also have an effect on the functioning of the brainstem respiratory neural network, which could ultimately reinforce or accentuate ventilatory alterations. To this end, we sought to uncover the consequences of pulmonary fibrosis on ventilatory variables and how the modification of pulmonary rigidity could influence the functioning of the respiratory neuronal network. In a mouse model of pulmonary fibrosis obtained by 6 repeated intratracheal instillations of bleomycin (BLM), we first observed an increase in minute ventilation characterised by an increase in respiratory rate and tidal volume, a desaturation and a decrease in lung compliance. The changes in these ventilatory variables were correlated with the severity of the lung injury. The impact of lung fibrosis was also evaluated on the functioning of the medullary areas involved in the elaboration of the central respiratory drive. Thus, BLM-induced pulmonary fibrosis led to a change in the long-term activity of the medullary neuronal respiratory network, especially at the level of the nucleus of the solitary tract, the first central relay of the peripheral afferents, and the Pre-Bötzinger complex, the inspiratory rhythm generator. Our results showed that pulmonary fibrosis induced modifications not only of pulmonary architecture but also of central control of the respiratory neural network.

Breathing irregularities in spontaneously hypertensive neonate rats

An excessive sympathetic drive is commonly observed in hypertensive patients and critically contributes to increasing arterial pressure levels. The quality of postnatal life can impact sympathetic control in adulthood. Spontaneously hypertensive (SH) rats, an experimental model of neurogenic hypertension, exhibit breathing irregularities in adult life. In this study, we investigated whether SH rats display breathing abnormalities after birth, which could be a risk factor for developing sympathetic overactivity. Using head-out plethysmography, we found that the neonate (P0-2, male and female) SH rats (n=9) exhibited lower minute ventilation than age-matched normotensive rats (NT, n=14; 816±177 vs 1261±189 ml/min/kg, P&lt;0.05) under resting conditions, mainly due to reductions in respiratory frequency (93±15 vs 132±13 cpm, P&lt;0.05). The reduced baseline ventilation in the SH group was accompanied by a greater prevalence of periods of apneas and respiratory irregularities (P&lt;0.05). Under hypoxia conditions (10% O2, 10 min), SH and NT rats (n=9/each) mounted similar transient increases in minute ventilation during the initial period of exposure due to increments in tidal volume. In contrast, the respiratory frequency in the SH rats decreased progressively below baseline levels during hypoxia exposure (42% reduction, P&lt;0.05), while it remained similar to pre-hypoxia values in the control group. In rhythmic in vitro preparations from neonate SH rats (n=2), we identified ectopic bursts in the hypoglossal activity and prolonged inspiratory-related bursts in the preBötzinger complex compared to preparations from NT rats (n=2). Our findings indicate that breathing irregularities in SH rats are present from birth and could be linked to dysfunctions in the inspiratory rhythm-generating network. Financial support: FAPESP, CNPq. 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.