Hypercapnic Conditions Research Articles

A Fluorescent Probe Containing Triphenylamine-Benzofuranone Moiety for Detecting Cysteine and Imaging in Living Pulmonary Cells Under Hypercapnia.

In this work, a fluorescent probe TPB-Cys derived from triphenylamine-benzofuranone was developed for monitoring the cysteine (Cys) level and imaging in living pulmonary cells under hypercapnia condition. A systematic hypoxia module was tried to cover both the in-solution test and pulmonary cellular imaging. The hypoxia condition did not obviously affect the fluorescence response signal during the in-solution test. The fluorescence signal at 540 enhanced in a dose-dependent enhancement along with the increase of the Cys concentration. The probe showed the advantages including relatively long linear range, high sensitivity, high stability, and high selectivity. With low cyto-toxicity, TPB-Cys achieved the monitoring of the endogenous Cys level in living pulmonary cells. Furthermore, it also realized the visualization of the affection of the hypoxia and hypoxia recovered conditions. This work was informative for both the accurate diagnosis and potential medical techniques.

The effect of CO2 on the age dependence of neurovascular coupling.

Prior studies have identified variable effects of aging on neurovascular coupling (NVC). Carbon dioxide (CO2) affects both cerebral blood velocity (CBv) and NVC, but the effects of age on NVC under different CO2 conditions are unknown. Therefore, we investigated the effects of aging on NVC in different CO2 states during cognitive paradigms. Seventy-eight participants (18-78 yr), with well-controlled comorbidities, underwent continuous recordings of CBv by bilateral insonation of middle (MCA) and posterior (PCA) cerebral arteries (transcranial Doppler), blood pressure, end-tidal CO2, and heart rate during poikilocapnia, hypercapnia (5% CO2 inhalation), and hypocapnia (paced hyperventilation). Neuroactivation via visuospatial (VS) and attention tasks (AT) was used to stimulate NVC. Peak percentage and absolute change in MCAv/PCAv, were compared between CO2 conditions and age groups (≤30, 31-60, and >60 yr). For the VS task, in poikilocapnia, younger adults had a lower NVC response compared with older adults [mean difference (MD): -7.92% (standard deviation (SD): 2.37), P = 0.004], but comparable between younger and middle-aged groups. In hypercapnia, both younger [MD: -4.75% (SD: 1.56), P = 0.009] and middle [MD: -4.58% (SD: 1.69), P = 0.023] age groups had lower NVC responses compared with older adults. Finally, in hypocapnia, both older [MD: 5.92% (SD: 2.21), P = 0.025] and middle [MD: 5.44% (SD: 2.27), P = 0.049] age groups had greater NVC responses, compared with younger adults. In conclusion, the magnitude of NVC response suppression from baseline during hyper- and hypocapnia, did not differ significantly between age groups. However, the middle age group demonstrated a different NVC response while under hypercapnic conditions, compared with hypocapnia.NEW & NOTEWORTHY This study describes the effects of age on neurovascular coupling under altered CO2 conditions. We demonstrated that both hypercapnia and hypocapnia suppress neurovascular coupling (NVC) responses. Furthermore, that middle age exhibits an NVC response comparable with younger adults under hypercapnia, and older adults under hypocapnia.

Developing a fluorescent probe containing benzofuranone moiety for imaging sulphite in living hypoxia pulmonary cells.

In this work, a benzofuranone-derived fluorescent probe BFSF was developed for imaging the sulphite level in living hypoxia pulmonary cells. Under the excitation of 510 nm, BFSF showed a strong fluorescence response at 570 nm when reacted with sulphite. In the solution system, the constructed hypercapnia and serious hypercapnia conditions did not affect the fluorescence response. In comparison with the recently reported probes, BFSF suggested the advantages including rapid response, steady signal reporting, high specificity and low cytotoxicity upon living lung cells. Under a normal incubation atmosphere, BFSF realized the imaging of both exogenous and endogenous sulphite in living pulmonary cells. In particular, BFSF achieved imaging the decrease of the sulphite level under severe hypoxia as well as the recovery of the sulphite level with urgent oxygen supplement. With the imaging capability for the sulphite level in living pulmonary cells under hypoxia conditions, BFSF together with the information herein was meaningful for investigating the anaesthesia-related biological indexes.

Translational insights into the hormetic potential of carbon dioxide: from physiological mechanisms to innovative adjunct therapeutic potential for cancer.

Carbon dioxide (CO2), traditionally viewed as a mere byproduct of cellular respiration, plays a multifaceted role in human physiology beyond simple elimination through respiration. CO2 may regulate the tumor microenvironment by significantly affecting the release of oxygen (O2) to tissues through the Bohr effect and by modulating blood pH and vasodilation. Previous studies suggest hypercapnia (elevated CO2 levels) might trigger optimized cellular mechanisms with potential therapeutic benefits. The role of CO2 in cellular stress conditions within tumor environments and its impact on O2 utilization offers a new investigative area in oncology. This study aims to explore CO2's role in the tumor environment, particularly how its physiological properties and adaptive responses can influence therapeutic strategies. By applying a structured translational approach using the Work Breakdown Structure method, the study divided the analysis into six interconnected work packages to comprehensively analyze the interactions between carbon dioxide and the tumor microenvironment. Methods included systematic literature reviews, data analyses, data integration for identifying critical success factors and exploring extracellular environment modulation. The research used SMART criteria for assessing innovation and the applicability of results. The research revealed that the human body's adaptability to hypercapnic conditions could potentially inform innovative strategies for manipulating the tumor microenvironment. This could enhance O2 utilization efficiency and manage adaptive responses to cellular stress. The study proposed that carbon dioxide's hormetic potential could induce beneficial responses in the tumor microenvironment, prompting clinical protocols for experimental validation. The research underscored the importance of pH regulation, emphasizing CO2 and carbonic acid's role in modulating metabolic and signaling pathways related to cancer. The study underscores CO2 as vital to our physiology and suggests potential therapeutic uses within the tumor microenvironment. pH modulation and cellular oxygenation optimization via CO2 manipulation could offer innovative strategies to enhance existing cancer therapies. These findings encourage further exploration of CO2's therapeutic potential. Future research should focus on experimental validation and exploration of clinical applications, emphasizing the need for interdisciplinary and collaborative approaches to tackle current challenges in cancer treatment.

A multi-objective optimisation approach for the linear modelling of cerebral autoregulation system

Objective:Dynamic cerebral autoregulation (dCA) has been addressed through different approaches for discriminating between normal and impaired conditions based on spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CF). This work presents a novel multi-objective optimisation (MO) approach for finding good configurations of a cerebrovascular resistance-compliance model. Methods:Data from twenty-nine subjects under normo and hypercapnic (5% CO2 in air) conditions was used. Cerebrovascular resistance and vessel compliance models with ABP as input and CF velocity as output were fitted using a MO approach, considering fitting Pearson’s correlation and error. Results:MO approach finds better model configurations than the single-objective (SO) approach, especially for hypercapnic conditions. In addition, the Pareto-optimal front from the multi-objective approach enables new information on dCA, reflecting a higher contribution of myogenic mechanism for explaining dCA impairment.

The effects of prolonged sitting with a mild hypercapnic environment on vascular function in elderly adults: A pilot study

Introduction: Prolonged Sitting (PS), defined a sitting for 2+ hours at a time, has been identified as an independent risk factor for cardiovascular disease (CVD). We previously reported that an acute bout of PS can attenuate macrovascular function in healthy young adults. Additionally, we reported that PS in mild hypercapnic environments (elevated CO2 concentrations) can further exacerbate these impairments in healthy young adults, and these impairments can be partially prevented by intermittent bouts of passive and active leg movements. However, the effects of prolonged sitting with a mild hypercapnic environment in the elderly population have not been studied. Therefore, the purpose of this study was to examine the impact of prolonged sitting with a mild hypercapnic condition on macrovascular function, arterial stiffness, and leg muscle metabolism. Additionally, we have further examined the effects of passive and active movements to negate the negative effects of prolonged sitting in elderly adults. Hypothesis: We hypothesized that 1) prolonged sitting in a hypercapnic environment will attenuate vascular function and leg metabolism, 2) both passive and active leg movements will preserve endothelial function and leg metabolism. Methods: Healthy elderly adults (n=2, 2 males, 69 ± 2.83 yrs) participated in three experimental visits consisting of 2.5h of prolonged sitting in a mild hypercapnic condition (CO2 = 1500ppm): control (CON), passive (PASS, passive leg movement), and active (ACT, active leg movement). Popliteal and brachial artery endothelial function was measured using flow-mediated dilation (FMD). Peripheral and central arterial stiffness was assessed using pulse wave velocity. Leg muscle metabolism was assessed using near infrared spectroscopy and a thermal camera. All measurements were taken pre- and post-siting. Results: Popliteal FMD was reduced in the CON condition compared to both the PASS and ACT (Δ -3.559 ± 0.499 vs Δ -1.799 ± 0.824 vs Δ 0.601 ± 1.958, respectively). Brachial FMD was attenuated in the CON condition compared to both compared to both the PASS and ACT (Δ -2.368 ± 0.215 vs Δ -0.285 ± 1.578 vs Δ 1.116 ± 1.174, respectively). The CON condition showed a greater reduction in leg temperature compared to both the PASS and ACT (Δ -2.4 vs Δ -1.6 ± 0.599 vs Δ 0.1 ± 0.224, respectively). No changes in central or peripheral arterial stiffness were observed. Conclusion: This preliminary data shows that uninterrupted prolonged sitting induces impairments in both local and systemic vascular function, leg muscle metabolism, but not arterial stiffness. Additionally, intermittent bouts of passive and active movements can partially preserve leg vascular function and metabolism during PS. This research was supported by the UNO Graduate Research and Creative Activity Grant, National Institutes of Health (RO1HD106911) and the Great Plains IdeaA-CTR (U54 GM115448). 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.

Baroreflex sensitivity is blunted in hypoxia independently of changes in inspired carbon dioxide pressure in prematurely born male adults.

Premature birth may result in specific cardiovascular responses to hypoxia and hypercapnia, that might hamper high-altitude acclimatization. This study investigated the consequences of premature birth on baroreflex sensitivity (BRS) under hypoxic, hypobaric and hypercapnic conditions. Seventeen preterm born males (gestational age, 29 ± 1 weeks), and 17 age-matched term born adults (40 ± 0 weeks) underwent consecutive 6-min stages breathing different oxygen and carbon dioxide concentrations at both sea-level and high-altitude (3375 m). Continuous blood pressure and ventilatory parameters were recorded in normobaric normoxia (NNx), normobaric normoxic hypercapnia (NNx + CO2 ), hypobaric hypoxia (HHx), hypobaric normoxia (HNx), hypobaric normoxia hypercapnia (HNx + CO2 ), and hypobaric hypoxia with end-tidal CO2 clamped at NNx value (HHx + clamp). BRS was assessed using the sequence method. Across all conditions, BRS was lower in term born compared to preterm (13.0 ± 7.5 vs. 21.2 ± 8.8 ms⋅mmHg-1 , main group effect: p < 0.01) participants. BRS was lower in HHx compared to NNx in term born (10.5 ± 4.9 vs. 16.0 ± 6.0 ms⋅mmHg-1 , p = 0.05), but not in preterm (27.3 ± 15.7 vs. 17.6 ± 8.3 ms⋅mmHg-1 , p = 0.43) participants, leading to a lower BRS in HHx in term born compared to preterm (p < 0.01). In conclusion, this study reports a blunted response of BRS during acute high-altitude exposure without any influence of changes in inspired CO2 in healthy prematurely born adults.

Modeling the mechanisms of non-neurogenic dynamic cerebral autoregulation.

Dynamic cerebral autoregulation (dCA) refers to a collection of mechanisms that act to maintain steady state cerebral blood flow (CBF) near constant despite changes in arterial blood pressure (ABP), but which is known to become impaired in various cerebrovascular diseases. Currently, the mechanisms of dCA and how they are affected in different physiological conditions are poorly understood. The objective of this study was to disentangle the magnitudes and time scales of the myogenic and metabolic responses of dCA, in order to investigate how each mechanism is affected in impaired dCA. A physiological model of dCA was developed, where both the myogenic and metabolic responses were represented by a gain and time constant. Model parameters were optimized with pressure-flow impulse responses under normocapnia, thigh cuff, and hypercapnia conditions. The impulse responses were derived by applying transfer function analysis (TFA) to experimental recordings of ABP (Finapres), end-tidal CO2 (capnograph), and CBF velocity (transcranial doppler ultrasound in bilateral middle cerebral arteries). The myogenic gain to time constant ratio was significantly smaller (p-values < 0.001 using both univariate and multivariate TFA), and the metabolic time constant was significantly larger (p-values < 0.001 using both univariate and multivariate TFA) in hypercapnia compared to normocapnia. Both the myogenic and metabolic responses were shown to be affected in impaired dCA, and the metabolic response was shown to be slowed down. This study contributes to the understanding of the complexities of dCA and how it is affected in different physiological conditions.

Impaired cerebrovascular CO2 reactivity at high altitude in prematurely born adults.

Premature birth impairs cardiac and ventilatory responses to both hypoxia and hypercapnia, but little is known about cerebrovascular responses. Both at sea level and after 2days at high altitude (3375m), 16 young preterm-born (gestational age, 29 ± 1weeks) and 15 age-matched term-born (40 ± 0weeks) adults were exposed to two consecutive 4min bouts of hyperoxic hypercapnic conditions (3% CO2 -97% O2 ; 6% CO2 -94% O2 ), followed by two periods of voluntary hyperventilation-induced hypocapnia. We measured middle cerebral artery blood velocity, end-tidal CO2 , pulmonary ventilation, beat-by-beat mean arterial pressure and arterialized capillary blood gases. Baseline middle cerebral artery blood velocity increased at high altitude compared with sea level in term-born (+24 ± 39%, P=0.036), but not in preterm-born (-4 ± 27%, P=0.278) adults. The end-tidal CO2 , pulmonary ventilation and mean arterial pressure were similar between groups at sea level and high altitude. Hypocapnic cerebrovascular reactivity was higher at high altitude compared with sea level in term-born adults (+173 ± 326%, P=0.026) but not in preterm-born adults (-21 ± 107%, P=0.572). Hypercapnic reactivity was altered at altitude only in preterm-born adults (+125 ± 144%, P<0.001). Collectively, at high altitude, term-born participants showed higher hypocapnic (P=0.012) and lower hypercapnic (P=0.020) CO2 reactivity compared with their preterm-born peers. In conclusion, exposure to high altitude revealed different cerebrovascular responses in preterm- compared with term-born adults, despite similar ventilatory responses. These findings suggest a blunted cerebrovascular response at high altitude in preterm-born adults, which might predispose these individuals to an increased risk of high-altitude illnesses. KEY POINTS: Cerebral haemodynamics and cerebrovascular reactivity in normoxia are known to be similar between term-born and prematurely born adults. In contrast, acute exposure to high altitude unveiled different cerebrovascular responses to hypoxia, hypercapnia and hypocapnia. In particular, cerebral vasodilatation was impaired in prematurely born adults, leading to an exaggerated cerebral vasoconstriction. Cardiovascular and ventilatory responses to both hypo- and hypercapnia at sea level and at high altitude were similar between control subjects and prematurely born adults. Other mechanisms might therefore underlie the observed blunted cerebral vasodilatory responses in preterm-born adults at high altitude.

The efficacy of intranasal leptin for opioid-induced respiratory depression depends on sex and obesity state.

Introduction: Opioid-induced respiratory depression (OIRD) is the primary cause of death associated with opioids and individuals with obesity are particularly susceptible due to comorbid obstructive sleep apnea (OSA). Repeated exposure to opioids, as in the case of pain management, results in diminished therapeutic effect and/or the need for higher doses to maintain the same effect. With limited means to address the negative impact of repeated exposure it is critical to develop drugs that prevent deaths induced by opioids without reducing beneficial analgesia. Methods: We hypothesized that OIRD as a result of chronic opioid use can be attenuated by administration of IN leptin while also maintaining analgesia in both lean mice and mice with diet-induced obesity (DIO) of both sexes. To test this hypothesis, an opioid tolerance protocol was developed and a model of OIRD in mice chronically receiving morphine and tolerant to morphine analgesia was established. Subsequently, breathing was recorded by barometric plethysmography in four experimental groups: obese male, obese female, lean male, and lean female following acute administration of IN leptin. Respiratory data were complemented with measures of arterial blood gas. Operant behavioral assays were used to determine the impact of IN leptin on the analgesic efficacy of morphine. Results: Acute administration of IN leptin significantly attenuated OIRD in DIO male mice decreasing the apnea index by 58.9% and apnea time by 60.1%. In lean mice leptin was ineffective. Blood gas measures confirmed the effectiveness of IN leptin for preventing respiratory acidosis in DIO male mice. However, IN leptin was not effective in lean mice of both sexes and appeared to exacerbate acid-base disturbances in DIO female mice. Additionally, morphine caused a complete loss of temperature aversion which was not reduced by intranasal leptin indicating IN leptin does not decrease morphine analgesia. Discussion: IN leptin effectively treated OIRD in morphine-tolerant DIO male mice without impacting analgesia. In contrast, IN leptin had no effect in lean mice of either sex or DIO female mice. The arterial blood gas data were consistent with ventilatory findings showing that IN leptin reversed morphine-induced respiratory acidosis only in DIO male mice but not in other mouse groups. Finally, a hypercapnic sensitivity study revealed that IN leptin rescued minute ventilation under hypercapnic conditions only in DIO male mice, which suggests that differential responses to IN leptin are attributable to different leptin sensitivities depending on sex and the obesity status.

Biofilm formation by basidiomycete and ascomycete yeasts in the intestines under different temperature and oxygen conditions

Aims. To evaluate the ability of biofilm formation by basidiomycete (Rhodotorula mucilaginosa, Trichosporon asahii) and ascomycete (Geotrichum candidum, Pichia kudriavzevii, Candida albicans) yeast isolated from the human intestine at different temperatures, under aerobic, anaerobic and hypercapnic conditions. Methods. Evaluation of biofilm formation was performed by measuring optical density. Flat-bottom plastic plates with test strains were incubated for 96 hours under aerobic conditions at 37°C and 25°C, under hypercapnic conditions (10% CO2) at 37°C, and under anaerobic conditions at 25°C. After incubation, the plates were washed three times with physiological saline, and the optical density of the formed microbial aggregates was check investigated photometrically. Results. It was found that C. albicans and P. kudriavzevii are capable of forming biofilms in all studied temperature and oxygen regimes. T. asahii formed biofilms only under aerobic conditions at the specified temperature regimes. G. candidum and Rh. mucilaginosa formed films under aerobic conditions only at 25°C. Conclusions. The ability of C. albicans and P. kudriavzevii to biofilm formation under temperature-oxygen conditions similar to the conditions of various biotopes of the human body allows substantiating the high pathogenic potential of these fungi. The need for aerobic conditions for T. asahii will partially explain its predominant parasitism on the skin and their appendages. The failure of G. candidum and Rh. mucilaginosa to biofilm formation under human conditions may indicate their low pathogenic potential.

Variability and controls of the ocean acidification metrics pH and pCO2 in a large embayment of an Eastern Boundary Upwelling System (EBUS)

An assessment was undertaken of the spatial and temporal variability of pCO2 and pH in St Helena Bay, a highly productive, wide-open bay located in the Benguela, a major eastern boundary upwelling system (EBUS). Mechanisms controlling their patterns of variability and their linkage to the distribution of oxygen are explored. The mean surface pCO2 was 385 μatm, below the mean atmospheric concentration of 410 μatm, indicative of a system serving as a CO2 sink. The corresponding mean pH of bay surface waters was 8.3. The greatest variation from these means was driven by deep winter mixing causing a seasonal reversal of the air-sea pCO2 gradient. Mean surface pCO2 was also elevated above mean atmospheric levels in the nearshore (<15 m depth), a likely consequence of higher microbial respiration in the upper water column due to regular resuspension of detrital material. The nearshore of the bay is also sometimes subject to high biomass dinoflagellate blooms referred to as red tides, and their decay leads to exceptional pCO2 concentrations. Discharge from the Berg River and the associated degradation of terrestrially derived organic matter also contributes to higher pCO2 in the nearshore particularly during winter when rainfall is highest. Through the water column the important role of photosynthesis in determining the vertical distribution of pCO2 is evident in that pCO2 is shown to be a function of both Chl a and PAR. In St Helena Bay nearly 50% of water column biomass is located below the community compensation depth (i.e. where respiration carbon loss exceeds gross community production) leading to rapidly declining O2 and increasing pCO2 concentrations with depth. Resulting conditions of bottom water hypoxia/anoxia are therefore accompanied by more corrosive waters (pH declining to ∼7.4) and conditions of severe hypercapnia (pCO2 exceeding 2000 μatm) subjecting marine life to multiple stressors. St Helena Bay and similar bays in EBUS are likely to provide extrema in the deoxygenation and acidification of coastal waters.

10-min exposure to a 2.5% hypercapnic environment increases cerebral blood blow but does not impact executive function

Space travel and exploration are associated with increased ambient CO2 (i.e., a hypercapnic environment). Some work reported that the physiological changes (e.g., increased cerebral blood flow [CBF]) associated with a chronic hypercapnic environment contributes to a “space fog” that adversely impacts cognition and psychomotor performance, whereas other work reported no change or a positive change. Here, we employed the antisaccade task to evaluate whether transient exposure to a hypercapnic environment influences top-down executive function (EF). Antisaccades require a goal-directed eye movement mirror-symmetrical to a target and are an ideal tool for identifying subtle EF changes. Healthy young adults (aged 19–25 years) performed blocks of antisaccade trials prior to (i.e., pre-intervention), during (i.e., concurrent) and after (i.e., post-intervention) 10-min of breathing factional inspired CO2 (FiCO2) of 2.5% (i.e., hypercapnic condition) and during a normocapnic (i.e., control) condition. In both conditions, CBF, ventilatory and cardiorespiratory responses were measured. Results showed that the hypercapnic condition increased CBF, ventilation and end-tidal CO2 and thus demonstrated an expected physiological adaptation to increased FiCO2. Notably, however, null hypothesis and equivalence tests indicated that concurrent and post-intervention antisaccade reaction times were refractory to the hypercapnic environment; that is, transient exposure to a FiCO2 of 2.5% did not produce a real-time or lingering influence on an oculomotor-based measure of EF. Accordingly, results provide a framework that – in part – establishes the FiCO2 percentage and timeline by which high-level EF can be maintained. Future work will explore CBF and EF dynamics during chronic hypercapnic exposure as more direct proxy for the challenges of space flight and exploration.

EPD1504: a novel μ-opioid receptor partial agonist attenuates obsessive-compulsive disorder (OCD)-like behaviors.

Low doses of μ-opioid receptor (MOR) agonists rapidly ameliorate symptoms in treatment-resistant obsessive-compulsive disorder (OCD) patients (10-50% of OCD patients). However, the utility of MOR agonists is limited by their safety liabilities. We developed a novel MOR partial agonist (EPD1540) that has an improved respiratory safety profile when compared to buprenorphine. Buprenorphine is a MOR partial agonist primarily used in the treatment of opiate-use disorder, which in investigator-led trials, has been shown to rapidly ameliorate symptoms in treatment-resistant OCD patients. In this study, we show that doses of EPD1504 and buprenorphine that occupy small fractions of MORs in the CNS (approximately 20%) are as effective as fluoxetine at ameliorating OCD-like behaviors in two different rat models (an operant probabilistic reversal task and marble burying). Importantly, effective doses of EPD1504 did not impair either locomotor activity, or respiration under normoxic or hypercapnic conditions. Additionally, EPD1504 had effects comparable to buprenorphine in the conditioned place preference assay. These results indicate that EPD1504 may provide a safer alternative to buprenorphine for the treatment of OCD patients.

Cerebral hemodynamics comparison using transcranial doppler ultrasound and 4D flow MRI.

Introduction: Age-related changes in cerebral hemodynamics are controversial and discrepancies may be due to experimental techniques. As such, the purpose of this study was to compare cerebral hemodynamics measurements of the middle cerebral artery (MCA) between transcranial Doppler ultrasound (TCD) and four-dimensional flow MRI (4D flow MRI). Methods: Twenty young (25 ± 3years) and 19 older (62 ± 6years) participants underwent two randomized study visits to evaluate hemodynamics at baseline (normocapnia) and in response to stepped hypercapnia (4% CO2, and 6% CO2) using TCD and 4D flow MRI. Cerebral hemodynamic measures included MCA velocity, MCA flow, cerebral pulsatility index (PI) and cerebrovascular reactivity to hypercapnia. MCA flow was only assessed using 4D flow MRI. Results: MCA velocity between the TCD and 4D flow MRI methods was positively correlated across the normocapnia and hypercapnia conditions (r = 0.262; p = 0.004). Additionally, cerebral PI was significantly correlated between TCD and 4D flow MRI across the conditions (r = 0.236; p = 0.010). However, there was no significant association between MCA velocity using TCD and MCA flow using 4D flow MRI across the conditions (r = 0.079; p = 0.397). When age-associated differences in cerebrovascular reactivity using conductance were compared using both methodologies, cerebrovascular reactivity was greater in young adults compared to older adults when using 4D flow MRI (2.11 ± 1.68mL/min/mmHg/mmHg vs. 0.78 ± 1.68mL/min/mmHg/mmHg; p = 0.019), but not with TCD (0.88 ± 1.01cm/s/mmHg/mmHg vs. 0.68 ± 0.94cm/s/mmHg/mmHg; p = 0.513). Conclusion: Our results demonstrated good agreement between the methods at measuring MCA velocity during normocapnia and in response to hypercapnia, but MCA velocity and MCA flow were not related. In addition, measurements using 4D flow MRI revealed effects of aging on cerebral hemodynamics that were not apparent using TCD.

Nordic Walking in Water on Cerebrovascular Reactivity and Cognitive Function in Elderly Patients with Type 2 Diabetes.

Aquatic Nordic walking (ANW) is a novel whole-body low-impact exercise that can be practiced by a variety of older adults with chronic conditions. However, its efficacy on several aspects of health is largely unknown. This study aimed to determine the effects of regular ANW on glycemic control and vascular function in older adults with type 2 diabetes and mild cognitive impairment. Thirty-three older adults with type 2 diabetes age 60-75 yr were randomly allocated to nonexercising control ( n = 17) or ANW ( n = 17) groups. Nordic walking was performed in a pool at water temperature of 34°C-36°C, three times per week for 12 wk. Measures of functional physical fitness including chair stand, timed up and go, chair sit and reach, reach and back scratch, and 6-min walk test scores were all improved after ANW (all P < 0.05). Plasma glucose, glycosylated hemoglobin, and homeostasis model assessment of insulin resistance decreased (all P < 0.05) in ANW. Vascular reactivity as assessed by brachial flow-mediated dilation increased, and arterial stiffness as assessed by brachial-ankle pulse wave velocity decreased in ANW (all P < 0.05). No significant changes were observed in the control group. Middle cerebral artery pulsatility index decreased with ANW under normocapnia condition ( P < 0.05). Cerebrovascular conductance increased with ANW under hypercapnia condition. Montreal Cognitive Assessment score increased in the ANW group ( P < 0.001). Changes in Montreal Cognitive Assessment scores were positively associated with corresponding changes in brain-derived neurotrophic factor ( r = 0.540, P = 0.031). Nordic walking in water was a safe and effective innovative exercise modality to improve glycemic control, vascular function, physical fitness, cerebrovascular reactivity, and cognitive function in older adults with type 2 diabetes.

In Vivo Testing of an Ambient Air Based, Portable, and Automated CO 2 Removal Controller for Artificial Lungs.

Portable artificial lung (AL) systems are under development, but there are few technologies available that adjust the carbon dioxide (CO 2 ) removal in response to changes in patient metabolic needs. Our work describes the second generation of a CO 2 -based portable servoregulation system that automatically adjusts CO 2 removal in ALs. Four adult sheep (68 ± 14.3 kg) were used to test the servoregulator. The servoregulator controlled air sweep flow through the lung to meet a target exhaust gas CO 2 (tEGCO 2 ) level in normocapnic and hypercapnic (arterial partial pressure of CO 2 [PaCO 2 ] >60 mm Hg) conditions at varying flow rates (0.5-1.5 L/min) and at tEGCO 2 levels of 10, 20, and 40 mm Hg. In hypercapnic sheep, average post-AL blood partial pressure of CO 2 (pCO 2 ) values were 22.4 ± 3.6 mm Hg for tEGCO 2 of 10 mm Hg, 28.0 ± 4.1 mm Hg for tEGCO 2 of 20 mm Hg and 40.6 ± 4.8 mm Hg for tEGCO 2 of 40 mm Hg. The controller successfully and automatically adjusted the sweep gas flow to rapidly (<10 minutes) meet the tEGCO 2 level when challenged with changes in inlet blood flow or target EGCO 2 levels for all animals. These in vivo data demonstrate an important step toward portable ALs that can automatically modulate CO 2 removal and allow for substantial changes in patient activity or disease status in ambulatory applications.

Electrophysiological properties and phenotype of the expiratory lateral parafacial neurons of rats

Active expiration is essential for increasing pulmonary ventilation during high chemical drive (hypercapnia). Several studies demonstrated that the lateral aspect of the parafacial (pFL) region, which contains expiratory neurons, drives abdominal muscles during active expiration in response to hypercapnia. However, the electrophysiological properties and synaptic mechanisms determining the activity of pFL expiratory neurons and the specific conditions for their emergence are not fully understood. Therefore, using whole-cell electrophysiology and single-cell qRT-PCR techniques, we evaluated the intrinsic electrophysiological properties, the phenotype, and the respiratory-related synaptic inputs to the pFL expiratory neurons, as well as the mechanisms for the expression of their expiratory activity under conditions of hypercapnia induced active expiration in in situ preparations of juvenile rats. We also evaluated whether these neurons possess intrinsic CO 2 /[H + ] sensitivity. All recorded pFL expiratory neurons were glutamatergic. In normocapnia, GABAergic and glycinergic inhibition during inspiration and expiration suppressed the activity of excitatory pFL expiratory neurons. In hypercapnia, these neurons escape glycinergic inhibition and generate burst discharges at the end of expiration. Post-inhibitory rebound, Ca V 3.2 isoform of T-type Ca 2+ channels, and intracellular [Ca 2+ ] contribute to their expiratory activity. Hypercapnia/hypocapnia or acidosis/alkalosis did not affect the activity of pFL expiratory neurons, indicating that these neurons do not possess intrinsic CO2 and pH sensitivity. Additionally, ion channels/receptors (TASK or GPR4) related to CO 2 /[H + ] sensitivity were not expressed by pFL expiratory neurons. In conclusion, the intrinsic electrophysiological properties and post-synaptic disinhibition of glutamatergic neurons both play essential roles in generating the expiratory oscillations in the pFL region during hypercapnia in rats. FAPESP and 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.

Carbon dioxide protects simulated driving performance during severe hypoxia

PurposeWe sought to determine the effect of acute severe hypoxia, with and without concurrent manipulation of carbon dioxide (CO2), on complex real-world psychomotor task performance.MethodsTwenty-one participants completed a 10-min simulated driving task while breathing room air (normoxia) or hypoxic air (PETO2 = 45 mmHg) under poikilocapnic, isocapnic, and hypercapnic conditions (PETCO2 = not manipulated, clamped at baseline, and clamped at baseline + 10 mmHg, respectively). Driving performance was assessed using a fixed-base motor vehicle simulator. Oxygenation in the frontal cortex was measured using functional near-infrared spectroscopy.ResultsSpeed limit exceedances were greater during the poikilocapnic than normoxic, hypercapnic, and isocapnic conditions (mean exceedances: 8, 4, 5, and 7, respectively; all p ≤ 0.05 vs poikilocapnic hypoxia). Vehicle speed was greater in the poikilocapnic than normoxic and hypercapnic conditions (mean difference: 0.35 km h−1 and 0.67 km h−1, respectively). All hypoxic conditions similarly decreased cerebral oxyhaemoglobin and increased deoxyhaemoglobin, compared to normoxic baseline, while total hemoglobin remained unchanged.ConclusionsThese findings demonstrate that supplemental CO2 can confer a neuroprotective effect by offsetting impairments in complex psychomotor task performance evoked by severe poikilocapnic hypoxia; however, differences in performance are unlikely to be linked to measurable differences in cerebral oxygenation.

The effect of transcutaneous electrical stimulation of the submental area on the cardiorespiratory response in normal and awake subjects.

Background: Electrical stimulation has recently been introduced to treat patients with Obstructive sleep apnoea There are, however, few data on the effects of transcutaneous submental electrical stimulation (TES) on the cardiovascular system. We studied the effect of TES on cardiorespiratory variables in healthy volunteers during head-down-tilt (HDT) induced baroreceptor loading. Method: Cardiorespiratory parameters (blood pressure, heart rate, respiratory rate, tidal volume, airflow/minute ventilation, oxygen saturation, and end-tidal CO2/O2 concentration) were recorded seated, supine, and during head-down-tilt (50) under normoxic, hypercapnic (FiCO2 5%) and poikilocapnic hypoxic (FiO2 12%) conditions. Blood pressure (BP) was measured non-invasively and continuously (Finapres). Gas conditions were applied in random order. All participants were studied twice on different days, once without and once with TES. Results: We studied 13 healthy subjects (age 29 (12) years, six female, body mass index (BMI) 23.23 (1.6) kg·m-2). A three-way ANOVA indicated that BP decreased significantly with TES (systolic: p = 4.93E-06, diastolic: p = 3.48E-09, mean: p = 3.88E-08). Change in gas condition (systolic: p = 0.0402, diastolic: p = 0.0033, mean: p = 0.0034) and different postures (systolic: 8.49E-08, diastolic: p = 6.91E-04, mean: p = 5.47E-05) similarly impacted on BP control. When tested for interaction, there were no significant associations between the three different factors electrical stimulation, gas condition, or posture, except for an effect on minute ventilation (gas condition/posture p = 0.0369). Conclusion: Transcutaneous electrical stimulation has a substantial impact on the blood pressure. Similarly, postural changes and variations in inspired gas impact on blood pressure control. Finally, there was an interaction between posture and inspired gases that affects minute ventilation. These observations have implications on our understanding of integrated cardiorespiratory control, and may prove beneficial for patients with SDB who are assessed for treatment with electrical stimulation.