End-tidal PCO2 Research Articles

Deep brain stimulation of the motor thalamus relieves experimentally induced air hunger.

We previously reported that Deep Brain Stimulation (DBS) of motor thalamus (MT), in a patient with post-stroke tremor, relieved breathlessness associated with chronic obstructive pulmonary disease. This raised the question of whether MT DBS mitigates the ascending dyspnoea signal. We therefore sought to conduct a fully powered cohort study of experimentally induced air hunger (AH), an uncomfortable urge to breathe in patients with MT DBS ON and OFF. 16 patients (3 females) with DBS of the ventral intermediate nucleus (VIM) as treatment for tremor, underwent hypercapnic AH tests, with DBS "ON" and "OFF". Patients rated AH on a visual analogue scale (VAS) every 15 s. Hypercapnia and ventilation were matched for ON and OFF states (mean±sd 43±4 and 43±4 mmHg for end-tidal PCO2, 13.7 and 13.4 L·min-1 for ventilation). Participants ventilation was constrained to baseline levels by breathing from a 3-litre inspiratory reservoir with fixed flow of fresh gas while targeting their resting breathing frequency to a metronome. Overall steady state AH was 52±28%VAS for "ON" and 67±20%VAS for "OFF" (p=0.002; two-tailed paired t-test). The mean reduction in AH during VIM DBS was -14.4%VAS. MT DBS relieved AH in thirteen patients, heightened AH in two and caused no change in one. MT DBS for tremor relief also mitigates the AH component of dyspnoea. We posit that DBS of the MT heightens the gating control of the thalamus modulating the ascending air hunger signal. Extent of relief suggests that thalamic DBS may prove to be a viable therapy for intractable dyspnoea.

Effects of slowed respiratory rate and elevated end-tidal PCO2 during jogging on physiological responses

Effects of slowed respiratory rate and elevated end-tidal PCO2 during jogging on physiological responses

End-tidal-to-arterial PCO2 ratio as a prognostic value in mechanically ventilated patients at respiratory intensive care unit

Background Dead space refers to the part of each tidal volume that does not contribute to gas exchange. It serves as an indicator of lung function efficiency. Aim To evaluate the end-tidal-to-arterial PCO2 ratio and Acute Physiological and Chronic Health Assessment (APACHE IV) scoring system as prognostic values in mechanically ventilated patients at the respiratory intensive care unit (ICU). Patients and methods This prospective cohort research was done on 40 mechanically ventilated patients due to different respiratory causes who were admitted at the respiratory ICU at Ain Shams University hospitals. Results This study found that decreasing end tidal PCO2 (PETCO2)/arterial carbon dioxide (PaCO2) is associated with higher mortality amongst mechanically ventilated cases in respiratory ICU. A significant negative association between APACHE IV score and end-tidal to arterial PCO2 ratio following 1 h and after 24 h of mechanical ventilation. APACHE IV score showed a significant relation with mortality, being higher in survivors than nonsurvivors. Conclusion PETCO2/PaCO2 is a relevant prognostic value that reflects dead space ventilation among mechanically ventilated patients in respiratory ICU. APACHE IV score is a good mortality predictor in respiratory ICU.

Variability of Resting Carbon Dioxide Tension in Patients with Intracranial Steno-occlusive Disease.

Introduction Controlling the partial pressure of carbon dioxide (PaCO 2 ) is an important consideration in patients with intracranial steno-occlusive disease to avoid reductions in critical perfusion from vasoconstriction due to hypocapnia, or reductions in blood flow due to steal physiology during hypercapnia. However, the normal range for resting PCO 2 in this patient population is not known. Therefore, we investigated the variability in resting end-tidal PCO 2 (P ET CO 2 ) in patients with intracranial steno-occlusive disease and the impact of revascularization on resting P ET CO 2 in these patients. Setting and Design Tertiary care center, retrospective chart review Materials and Methods We collected resting P ET CO 2 values in adult patients with intracranial steno-occlusive disease who presented to our institution between January 2010 and June 2021. We also explored postrevascularization changes in resting P ET CO 2 in a subset of patients. Results Two hundred and twenty-seven patients were included [moyamoya vasculopathy ( n = 98) and intracranial atherosclerotic disease ( n = 129)]. In the whole cohort, mean ± standard deviation resting P ET CO 2 was 37.8 ± 3.9 mm Hg (range: 26-47). In patients with moyamoya vasculopathy and intracranial atherosclerotic disease, resting P ET CO 2 was 38.4 ± 3.6 mm Hg (range: 28-47) and 37.4 ± 4.1 mm Hg (range: 26-46), respectively. A trend was identified suggesting increasing resting P ET CO 2 after revascularization in patients with low preoperative resting P ET CO 2 (<38 mm Hg) and decreasing resting P ET CO 2 after revascularization in patients with high preoperative resting P ET CO 2 (>38 mm Hg). Conclusion This study demonstrates that resting P ET CO 2 in patients with intracranial steno-occlusive disease is highly variable. In some patients, there was a change in resting P ET CO 2 after a revascularization procedure.

Ventilatory response of peripheral chemoreceptors to hypercapnia during exercise above the respiratory compensation point.

Peripheral hypercapnic chemosensitivity (PHC) is assessed as the change in ventilation in response to a rapid change in carbon dioxide pressures (PCO2). The increase in chemoresponse from rest to sub-respiratory compensation point (RCP) exercise intensities is well-defined but less clear at intensities above the RCP when changes in known ventilatory stimulants occur. Twenty healthy subjects (n=10 females) completed a maximal exercise test on one day and on a subsequent day, transient hypercapnia was used to test PHC at multiple exercise stages. The transient hypercapnia involved two breaths of 10% CO2 repeated five times during each of the following: sitting at rest on the cycle ergometer, cycling at 40% Wmax, cycling at 85% Wmax, at rest on the cycle ergometer immediately following the 85% stage, and cycling at 40% Wmax again following the post-exercise rest. The PHC was not different across exercise intensities (0.98±0.37 vs. 0.91±0.39 vs. 0.92±0.42 L min-1 mmHg-1 for 1st 40% Wmax, 85% Wmax, and 2nd 40% Wmax, respectively (p=0.45). There were no differences in PHC between pre-supra-RCP exercise rest and post-supra-RCP exercise rest (0.52±0.23 vs. 0.53±0.24 L min-1 mmHg-1, p=0.8003). Using a repeated measures correlation to account for within participants changes, there was a significant relationship between the end-tidal PCO2 and PHC for the 85% intensity (r=0.5, p<0.0001) when end-tidal PCO2 was dynamic between the trials. We conclude that the physiological changes (e.g. metabolic milieu, temperature, etc) produced with supra-RCP exercise do not further augment PHC, and that the pre-stimulus end-tidal PCO2 modulates the PHC.

Midazolam for Post-Arrest Sedation in Pre-Hospital Emergency Care.

An out-of-hospital cardiac arrest (OHCA) with return of spontaneous circulation (ROSC) may need to be treated with airway management, emergency ventilation, invasive interventions, and post-arrest sedation. We investigated the influence of the use of midazolam for post-arrest sedation on achieving postresuscitation care targets and the associated risk of hemodynamic complications. All emergency rescue missions of the Dresden, Gütersloh, and Lippe medical rescue services in the years 2019-2021 were reviewed to identify adult patients who had OHCA, unconsciousness, and sustained ROSC with spontaneous circulation until arrival at the hospital; the findings were supplemented with data from the German Resuscitation Registry. Patients who received midazolam (alone or in combination with other anesthetic agents) for post-arrest sedation were compared with those who did not. The endpoints were the regaining of a systolic blood pressure ≥ 100 mmHg, end-tidal pCO2 35-45 mmHg, and oxygen saturation (SpO2) 94-98%. A propensity score analysis was used to adjust for age, sex, and variables potentially affecting hemodynamic status or the targets for oxygenation and ventilation. There were 2335 cases of OHCA among 391 305 emer - gency rescue missions. 571 patients had ROSC before arrival in the hospital (24.5%; female, 33.6%; age, 68 ± 14 years). Of the 395 among them (69.2%) who were treated with postarrest sedation, 249 (63.0%) received midazolam. Patients who received midazolam reached the guideline- recommended targets for oxygenation, ventilation, and blood pressure more frequently than those who were not sedated: the respective odds ratios and 95% confidence intervals were 2.00 [1.20; 3.34], 1.57 [0.99; 2.48], and 1.41 [0.89; 2.21]. The pre-hospital administration of midazolam leads to more frequent pre-hospital attainment of the oxygenation and ventilation targets in post-resuscitation care, without any evidence of an elevated risk of hemodynamic complications.

Blunted perception of breathlessness in three cases of low grade insular-glioma.

Better understanding of breathlessness perception addresses an unmet clinical need for more effective treatments for intractable dyspnoea, a prevalent symptom of multiple medical conditions. The insular-cortex is predominantly activated in brain-imaging studies of dyspnoea, but its precise role remains unclear. We measured experimentally-induced hypercapnic air-hunger in three insular-glioma patients before and after surgical resection. Tests involved one-minute increments in inspired CO2, raising end-tidal PCO2 to 7.5 mmHg above baseline (38.5 ± 5.7 mmHg), whilst ventilation was constrained (10.7 ± 2.3 L/min). Patients rated air-hunger on a visual analogue scale (VAS). Patients had lower stimulus-response (2.8 ± 2 vs. 11 ± 4 %VAS/mmHg; p = 0.004), but similar threshold (40.5 ± 3.9 vs. 43.2 ± 5.1 mmHg), compared to healthy individuals. Volunteered comments implicated diminished affective valence. After surgical resection; sensitivity increased in one patient, decreased in another, and other was unable to tolerate the ventilatory limit before any increase in inspired CO2.We suggest that functional insular-cortex is essential to register breathlessness unpleasantness and could be targeted with neuromodulation in chronically-breathless patients. Neurological patients with insula involvement should be monitored for blunted breathlessness to inform clinical management.

Abstract WP127: Diagnostic Value of the Ivy Sign Compared to MR With Cerebrovascular Reactivity in Decompensated Moyamoya Arteriopathy

Introduction: MR cerebrovascular reactivity (CVR) mapping during rapid manipulation of end-tidal pCO2 is used to assess hemodynamic compromise in patients with Moyamoya arteriopathy (MMA). Leptomeningeal ivy sign on MRI FLAIR sequence may indicate regions of decreased perfusion, which would be an inexpensive and easy way to screen for hemodynamic compromise. The purpose of this study was to examine the diagnostic value of the ivy sign compared to MR CVR. Methods: For this retrospective cross-sectional study, we included consecutive patients with uncompensated MMA who were eligible for extracranial-intracranial bypass surgery and completed a preoperative MRI FLAIR with CVR study. Patients with incomplete or artefact degraded imaging were excluded. Two neuroradiologists who were blinded for the CVR result independently assessed the degree of ivy sign on axial 2D FLAIR imaging as grade 0, 1 or 2 in 8 predefined brain regions. Two different readers, blinded for ivy sign, independently assessed the presence or absence of steal in the same regions on MR CVR. Consensus was reached for discordant findings. We assessed interrater agreement using weighted kappa followed by diagnostic accuracy measures for the ivy sign using MR CVR as a reference. Results: We enrolled 73 patients (41/73 (56.1%) female; mean age 43). 47/73 (64%) patients had bilateral MMA with on average 3 brain regions with abnormal CVR. Interrater agreement was good for ivy sign (weighted kappa 0.63 (95%CI 0.54-0.71)) and excellent for CVR (kappa 0.95 (95% CI 0.87-1.00)). For a total of 156/584 (26.7%) brain regions, there was agreement between a positive ivy sign and the presence of steal on CVR and 240/584 (41%) brain regions had no ivy sign and normal CVR. The sensitivity of the ivy sign was 64.5%, specificity 70.2%, positive predictive value 60.5% and negative predictive value 73.6% with an AUC of 0.68 (95% CI 0.64-0.72) Conclusions: In this preselected cohort with high pretest probability for hemodynamic compromise, the diagnostic accuracy of the ivy sign compared to MR CVR was limited and needs to be used with caution to determine haemodynamic status in MMA.

Does the Use of Auto-Transfusion Tourniquet (A-TT) during CPR Drill Influence its Quality Parameters?

The Auto-Transfusion Tourniquet (A-TT®) shifts the blood from the legs to the central circulation and blocks its return to the legs. The use of the A-TT has previously been shown to be effective during CPR and was shown in a pig study [1] to increase systolic and diastolic blood pressures, coronary perfusion pressure, cerebral perfusion and end-tidal PCO2. The present study was done to assess if using the A-TT as part of CPR protocol in pre-hospital cardiac arrest patients treated by a team of 4 caregivers interferes with the quality parameters of the CPR.

Pulmonary Rehabilitation for Chronic Lung Diseases.

Chronic Obstructive Pulmonary Disease (COPD) is now the main cause of disability in the developed world. The advance of COPD is related to increasing breathlessness, disability, and periodic hospitalizations. An aging population in the developed world and increasing cigarette consumption in developing countries expand the global impact of this condition. The disorder associated with COPD leads to a decrease in physical activity and failure of functional independence.&#x0D; The aim of this study was to evaluate the effects of PR in patients with normal exercise capacity on health-related quality of life and exercise capacity.&#x0D; The mean FEV1/FVC was 59.4± 14.1%, and the mean FEV1 was 64.8± 23.0% as expected. Most topics had mild to moderate COPD. The PImax and PEmax were normal. These subjects had no previous participation in home-based or hospital-based PR. All the subjects had normal maximal V˙O2 and work rate before PR.&#x0D; After PR there were still considerable improvements in maximal V˙O2 (mean increase of 101.3 mL/min, p &lt;0.001) and work rate (mean increase of 8.2 watts, p&lt;0.001). Ventilation, heart rate, and mean blood pressure were constant following PR. The maximum oxygen pulse at maximum exercise was significantly increased with PR (p&lt;0.02). The SpO2 and end-tidal PCO2 at peak exercise did not significantly improve after PR.&#x0D; Although dyspnea scores at rest were low and did not improve significantly with PR, dyspnea at end-exercise was significantly improved after PR (p=0.01). PR should be the responsibility of the clinical management of patients with COPD, even for those with normal exercise capacity. However, the benefits of disease progression, hospitalization, and survival for these patients remain unknown.&#x0D; The main role in the management of any chronic disease, including lung disease, is to improve the quality of life (QL) in patients.&#x0D; Conclusion; Although strongly recommended by scientific societies pulmonary rehabilitation programs still need to be more widely implemented. PR programs have shown a high level of evidence of benefits in chronic respiratory patients, particularly those with COPD.

Obstructive sleep apnea in children with Down syndrome: contribution of upper airway and chemosensitivity.

The high prevalence of obstructive sleep apnea syndrome (OSAS) in children with Down syndrome (DS) has been attributed to a reduced upper airway size, while the role of ventilatory control is unclear. The objectives of our case-control study were to evaluate the upper airway reduction in children with DS and moderate to severe OSAS as compared to typically developing (TD) children with similar OSAS severity and to evaluate the degree of chemical loop gain modifications including its components: controller and plant gains (CG, PG). Thirteen children with DS were matched for age, sex, OSAS severity and ethnicity with 26 TD children. They had undergone acoustic rhinometry and pharyngometry, chemical LG obtained during awake tidal breathing measurement and hypercapnic-hyperoxic ventilatory response testing. As compared to TD, children with DS depicted reduced oropharyngeal dimensions, significantly lower CG and LG and no different PG. Their hypercapnic ventilatory response slopes were not different. We concluded that the decreased CG in DS was related to decreased peripheral chemoreceptor sensitivity, and while central chemosensitivity was normal, the former explained the increased end-tidal PCO2 observed in children with DS as compared to TD. Pharyngeal dimensions are reduced in children with DS and OSAS. Reduced upper airway size and nocturnal alveolar hypoventilation in children with Down syndrome (DS) have been previously reported. We confirmed that children with DS and moderate-to-severe OSA have reduced oropharyngeal size as compared to typically developing children with similar OSAS severity and demonstrated decreased peripheral chemosensitivity explaining the alveolar hypoventilation observed in children with DS. Central chemosensitivity appears to be intact in children with DS and moderate to severe OSAS Our results support growing evidence that Down syndrome is associated with autonomic nervous system dysfunction.

Central CO2 chemosensitivity and CO2 controller gain independently contribute to daytime PCO2 in young subjects with congenital central hypoventilation syndrome.

Whether peripheral chemoreceptor response is altered in congenital central hypoventilation syndrome (CCHS) remains debated. Our aim was to prospectively evaluate both peripheral and central CO2 chemosensitivity and to evaluate their correlations with daytime PCO2 and arterial desaturation during exercise in CCHS. To this end, tidal breathing was recorded in CCHS patients allowing the calculation of loop gain and its components (steady-state controller [assumed to mainly be peripheral chemosensitivity] and plant gains using a bivariate [PETCO2 and ventilation] constrained model), a hyperoxic, hypercapnic ventilatory response test (central chemosensitivity), and a six-minute walk test (arterial desaturation). The results of loop gain were compared to those previously obtained in a healthy group of similar age. The study prospectively included 23 subjects with CCHS, without daytime ventilatory support; the subjects had a median age of 10 (5.6 to 27.4) years (15 females) with moderate polyalanine repeat mutation (PARM: 20/25, 20/26, n=11), severe PARM (20/27, 20/33, n=8), or non-PARM (n=4). As compared to 23 healthy subjects (4.9 to 27.0 years), the subjects with CCHS had a decreased controller gain and an increased plant gain. Mean daytime PETCO2 level of subjects with CCHS correlated negatively to both Log(controller gain) and the slope of CO2 response. Genotype was not related to chemosensitivity. Arterial desaturation on exercise correlated negatively with Log(controller) gain but not with the slope of the CO2 response. In conclusion, we demonstrate that peripheral CO2 chemosensitivity is altered in some patients with CCHS and that the daytime PETCO2 depends on central and peripheral chemoreceptor responses.

A biomarker of opioid-induced respiratory toxicity in experimental studies

Opioids are commonly used painkillers and drugs of abuse and have serious toxic effects including potentially lethal respiratory depression. It remains unknown which respiratory parameter is the most sensitive biomarker of opioid-induced respiratory depression (OIRD). To evaluate this issue, we studied 24 volunteers and measured resting ventilation, resting end-tidal PCO2 (PETCO2) and the hypercapnic ventilatory response (HCVR) before and at 1-h intervals following intake of the opioid tapentadol. Pharmacokinetic/pharmacodynamic analyses that included CO2 kinetics were applied to model the responses with focus on resting variables obtained without added CO2, HCVR slope and ventilation at an extrapolated PETCO2 of 55mmHg ( 55). The HCVR, particularly 55 followed by slope, was most sensitive in terms of potency; resting variables were least sensitive and responded slower to the opioid. Using 55 as biomarker in quantitative studies on OIRD allows standardized comparison among opioids in the assessment of their safety.

A Network approach to find poor orthostatic tolerance by simple tilt maneuvers.

The approach introduced by Network Physiology intends to find and quantify connectedness between close- and far related aspects of a person's Physiome. In this study I applied a Network-inspired analysis to a set of measurement data that had been assembled to detect prospective orthostatic intolerant subjects among people who were destined to go into Space for a two weeks mission. The advantage of this approach being that it is essentially model-free: no complex physiological model is required to interpret the data. This type of analysis is essentially applicable to many datasets where individuals must be found that "stand out from the crowd". The dataset consists of physiological variables measured in 22 participants (4f/18m; 12 prospective astronauts/cosmonauts, 10 healthy controls), in supine, + 30° and + 70° upright tilted positions. Steady state values of finger blood pressure and derived thereof: mean arterial pressure, heart rate, stroke volume, cardiac output, systemic vascular resistance; middle cerebral artery blood flow velocity and end-tidal pCO2 in tilted position were (%)-normalized for each participant to the supine position. This yielded averaged responses for each variable, with statistical spread. All variables i.e., the "average person's response" and a set of %-values defining each participant are presented as radar plots to make each ensemble transparent. Multivariate analysis for all values resulted in obvious dependencies and some unexpected ones. Most interesting is how individual participants maintained their blood pressure and brain blood flow. In fact, 13/22 participants had all normalized Δ-values (i.e., the deviation from the group average, normalized for the standard deviation), both for +30° and +70°, within the 95% range. The remaining group demonstrated miscellaneous response patterns, with one or more larger Δ-values, however of no consequence for orthostasis. The values from one prospective cosmonaut stood out as suspect. However, early morning standing blood pressure within 12h after return to Earth (without volume repletion) demonstrated no syncope. This study demonstrates an integrative way to model-free assess a large dataset, applying multivariate analysis and common sense derived from textbook physiology.

Inhaled Δ9-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers

BackgroundIn humans, the effect of cannabis on ventilatory control is poorly studied, and consequently, the effect of Δ9-tetrahydrocannabinol (THC) remains unknown, particularly when THC is combined with an opioid. We studied the effect of THC on breathing without and with oxycodone pretreatment. We hypothesised that THC causes respiratory depression, which is amplified when THC and oxycodone are combined. MethodsIn this randomised controlled crossover trial, healthy volunteers were administered inhaled Bedrocan® 100 mg (Bedrocan International B.V., Veendam, The Netherlands), a pharmaceutical-grade high-THC cannabis variant (21.8% THC; 0.1% cannabidiol), after placebo or oral oxycodone 20 mg pretreatment; THC was inhaled 1.5 and 4.5 h after placebo or oxycodone intake. The primary endpoint was isohypercapnic ventilation at an end-tidal Pco2 of 55 mm Hg or 7.3 kPa (VE55), measured at 1-h intervals for 7 h after placebo/oxycodone intake. ResultsIn 18 volunteers (age 22 yr [3]; 9 [50%] female), oxycodone produced a 30% decrease in VE55, whereas placebo was without effect on VE55. The first cannabis inhalation resulted in VE55 changing from 20.3 (3.1) to 23.8 (2.4) L min−1 (P=0.06) after placebo, and from 11.8 (2.8) to 13.0 (3.9) L min−1 (P=0.83) after oxycodone. The second cannabis inhalation also had no effect on VE55, but slightly increased sedation. ConclusionsIn humans, THC has no effect on ventilatory control after placebo or oxycodone pretreatment. Clinical trial registration2021-000083-29 (EU Clinical Trials Register.)

Clinical Safety and Performance Evaluation of New Personal Protective Equipment During the COVID-19 Pandemic

As the healthcare response to the COVID-19 pandemic continues, providing enhanced protection to frontline healthcare personnel exposed to aerosolized infectious material is essential. The rapid spread of the COVID-19 virus across the globe in early 2020 generated an overwhelming surge in demand for effective personal protective equipment (PPE), in particular, passive personal respirators (PPR). Global manufacturing of PPR was limited, and research and development of improved respirators were restricted by the availability of accredited laboratories for timely testing at the peak of the pandemic. The authors have described a clinical method of safety and efficacy testing of a new PPR, the TopBioShield, using portable capnography for the measurement of end-tidal pCO2 (ETCO2) and bedside pulse oximetry to measure oxygen saturation (SpO2), respiratory rate (RR), and heart rate (HR) in healthy volunteers to overcome shortages of clinical testing capabilities during the height of the pandemic. Twenty-eight volunteers with a median age of 41 years (range 16–71) representing all 10 subgroups of head/face size were included. Only one participant asked to withdraw due to a feeling of claustrophobia after 30 min. Clinical monitoring while wearing TopBioShield revealed ETCO2, SpO2, respiratory rate, and heart rate measurements were within normal limits in all the subjects throughout the experiment. Bedside clinical monitoring is effective in demonstrating the physiological safety of PPR and is an important alternative to conventional mannequin testing. In this study all measured values over a 90-min experiment period were within normal limits, demonstrating the effectiveness of TopBioShield in preventing CO2 retention. Clinical testing methods must adhere to the highest standards and are essential during times of shortage.

TILT TEST TOLERANCE AFTER TWO-WEEKS BED REST IN OLDER ADULTS IS NOT PROTECTED BY DAILY AEROBIC AND RESISTANCE EXERCISE

Abstract Bed rest is associated with increased risk of orthostatic intolerance on return to upright posture and, at least in young adults, regular exercise during bed rest is proposed as protective. 22 older adults (55-65 years, half women) participated in a randomized trial with 14-days of continuous 6-degree head-down bed rest. Half completed 60 min/day of aerobic and high-intensity interval cycling plus resistance exercises (Ex) while the other half were control (Con). A passive 80-degree head-up tilt (HUT) to a maximum of 15-min assessed orthostatic tolerance while cardio- and cerebrovascular responses were monitored to a pre-syncopal level of systolic blood pressure &amp;lt; 90 mmHg. In pre-bed rest baseline, all but 3 women (Ex) completed 15-min HUT. After 14-days bed rest, only 3 men (1 Ex) and 1 woman (Ex) completed 15-min with no differences in tolerance between men and women or Ex and Con. Vasovagal syncope presented in 5 participants (2 M-Con, 1 M-Ex, 1 F-Con, 1 F-Ex), most other non-finishers had progressive reduction in stroke volume without adequate vasoconstriction. Reductions in cerebral blood velocity measured during HUT by Doppler ultrasound revealed strong linear relationships to both end-tidal PCO2 and mean arterial pressure across all participants. These data indicate that neither older men nor older women were protected from orthostatic intolerance by 60-min per day exercise including high-intensity interval training. These data contrast with previous findings in younger adults in controlled trials of bed rest pointing to the need for greater understanding of mechanisms regulating blood pressure and brain blood flow.

Reproducibility of Respiratory Chemoreflex Characterization by Modified Rebreathing

Modified hypoxic and hyperoxic rebreathing is used to characterize central and peripheral respiratory chemoreflexes in humans. This study examined within‐ and between‐day reproducibility of the key parameters that are identified by this method: ventilatory recruitment threshold (VRT) and chemoreflex sensitivity. Seven healthy males (mean ± SD; age: 27±5 years) visited the laboratory on 4 occasions to performrepetitions of modified rebreathing tests in isoxic‐hypoxic (end‐tidal PO2 (PETO2) =50 mmHg) and ‐hyperoxic conditions (PETO2=150 mmHg). Days 1 and 2 consisted of three repeatedhyperoxic and three hypoxic trials, respectively; Days 3 and 4 included both a hyperoxic and a hypoxic trial completed in a counterbalanced order. Ventilation, end‐tidal PCO2 (PETCO2) and PETO2 were measured breath‐by‐breath by pneumotach and dual gas analyser. For each rebreathing trial, the PETCO2 at which ventilation began to rise was identified as the VRT (mmHg) and the slope of the response above VRT provided respiratory chemoreflex sensitivity (L∙min‐1∙mmHg‐1). Within‐ and between‐day reproducibility was assessed by one‐way ANOVA and intraclass correlation (ICC) analyses. The VRT was not different between trials performed on a single day for bothhyperoxic (44±2, 45±3, vs 44±3 mmHg; for Trials 1, 2, vs 3, respectively; p=0.50; ICC=0.926) and hypoxic rebreathing (40±3, 40±4, vs 40±4 mmHg; p=0.66; ICC=0.994). Chemoreflex sensitivity also was not different between trials performed on the same day in hyperoxic (4.3±2.2, 5.0±3.1, vs4.8±2.3 L∙min‐1∙mmHg‐1; p=0.33; ICC=0.955) or hypoxic conditions (5.6±2.2, 6.2±2.7, 5.7±2.0 L∙min‐1∙mmHg‐1; p=0.33; ICC=0.953). Between days, the VRT was not different for hyperoxic rebreathing (44±3 vs 44±2 vs 45±2 mmHg for Days 1, 3, vs 4, respectively; p=0.10; ICC=0.813) but was different for hypoxic rebreathing (40±3 vs 40±2 vs 41±3 mmHg for Days 2‐4, respectively; p=0.01; ICC=0.931). Chemoreflex sensitivity was not different between days for either hyperoxic (4.8±2.5,4.4±2.7, vs 4.9±2.0 L∙min‐1∙mmHg‐1; p=0.01; ICC=0.906) or hypoxic rebreathing (5.8±2.2, 5.8±2.6, vs 7.8±2.8 L∙min‐1∙mmHg‐1; p=0.01; ICC=0.750). Collectively, these data indicate that model parameters derived from hyperoxic and hypoxic modified rebreathing have good‐to‐excellent test‐retest reproducibility when repeated on the same or different days.

Perceptual and Ventilatory Responses to Hypercapnia in Athletes and Sedentary Individuals.

PurposeHypercapnic chemosensitivity traditionally captures the ventilatory response to elevated pressures of carbon dioxide in the blood. However, hypercapnia also contributes to subjective breathing perceptions, and previously we demonstrated a closer matching of perception to changes in ventilation in athletes compared to controls. Here we investigated any potential underlying hypercapnic chemosensitivity differences between groups, and explored whether these measures relate to ventilatory and perceptual responses during exercise as well as trait levels of affect.MethodsA hypercapnic challenge, incremental maximal exercise test and affective questionnaires were completed by 20 endurance athletes and 20 age-/sex-matched sedentary controls. The hypercapnic challenge involved elevating end-tidal PCO2 by 0.8% (6.1 mmHg) and 1.5% (11.2 mmHg) for 3 min each (randomised), with constant end-tidal oxygen. Ventilatory and perceptual responses to hypercapnia were compared between groups, and within each group the relationships between hypercapnic chemosensitivity (slope analyses) and exercising ventilation and perceptions were calculated using Spearman’s non-parametric correlations.ResultsWhile absolute ventilation differences during hypercapnia and exercise were observed, no group differences were found across hypercapnic chemosensitivity (slope) measures. Correlation analyses revealed the anxiety hypercapnic response was related to maximal exercise anxiety, but only in sedentary individuals.ConclusionVentilatory and perceptual hypercapnic chemosensitivity do not differ between athletes and sedentary individuals. However, ventilatory and anxiety hypercapnic chemosensitivities were related to ventilatory and anxiety responses during exercise in untrained individuals only. Athletes may employ additional strategies during exercise to reduce the influence of chemosensitivity on ventilatory and perceptual responses.

Neural respiratory drive in chronic thromboembolic pulmonary hypertension: Effect of balloon pulmonary angioplasty

Excessive ventilation (V̇E) during exercise, ascribed to heightened neural ventilatory drive and/or to increased “wasted” ventilation, is a feature of chronic thromboembolic pulmonary hypertension (CTEPH). In selected CTEPH patients, balloon pulmonary angioplasty (BPA) allows near-normalization of resting haemodynamic parameters but does not allow excess exercise hyperventilation to normalize. Neural ventilatory drive can be estimated by studying how arterial PCO2 (PaCO2), end-tidal PCO2 (PETCO2), V̇E and CO2 output (V̇CO2) change across the exercise-to-recovery transition during a cardiopulmonary exercise test. Increased “wasted” ventilation can be quantified by the physiological dead space fraction of tidal volume (VD/VT) calculated with the Enghoff simplification of the Bohr equation. These measurements were made before and after BPA in 22 CTEPH patients without significant cardiac and/or pulmonary comorbidities. Our observations suggest that before BPA, excessive hyperventilation was secondary to both heightened neural ventilatory drive and increased “wasted” ventilation; after BPA, measurements made across the exercise-to-recovery transition suggest that heightened neural ventilatory drive was no longer present.