Hypercapnic Conditions Research Articles

TRPV1 Inhibits the Ventilatory Response to Hypoxia in Adult Rats, but Not the CO₂-Drive to Breathe.

Receptors of the transient receptor potential (TRP) channels superfamily are expressed in many tissues and have different physiological functions. However, there are few studies investigating the role of these channels in cardiorespiratory control in mammals. We assessed the role of central and peripheral TRPV1 receptors in the cardiorespiratory responses to hypoxia (10% O2) and hypercapnia (7% CO2) by measuring pulmonary ventilation (), heart rate (HR), mean arterial pressure (MAP) and body temperature (Tb) of male Wistar rats before and after intraperitoneal (AMG9810 [2.85 µg/kg, 1 mL/kg]) or intracebroventricular (AMG9810 [2.85 µg/kg, 1 µL] or AMG7905 [28.5 μg/kg, 1 µL]) injections of TRPV1 antagonists. Central or peripheral injection of TRPV1 antagonists did not change cardiorespiratory parameters or Tb during room air and hypercapnic conditions. However, the hypoxic ventilatory response was exaggerated by both central and peripheral injection of AMG9810. In addition, the peripheral antagonist blunted the drop in Tb induced by hypoxia. Therefore, the current data provide evidence that TRPV1 channels exert an inhibitory modulation on the hypoxic drive to breathe and stimulate the Tb reduction during hypoxia.

Efektifitas Elevasi Kepala 300 Dalam Meningkatkan Perfusi Serebral Pada Pasien Post Trepanasi di Rumah Sakit Mitra Surabaya

Head trauma often causes cerebral perfusion disturbances that can cause some problems. Conditions of hypoxia, hypercapnia, hypotension and cerebral edema can cause further effect is increased intracranial pressure due to an increase in a confined space, reduced cerebral perfusion. so necessary actions to improve perfusion is by setting position of the head elevation 300 to increase cerebral venous drainage. The purpose of this study was to analyze the effectiveness of a 30° head-up positionin the post trepanation head injury patients in improving cerebral perfusion. This study used anonqui valent control group design. Post-op patient population trepanation head trauma in Hospital Mitra Keluarga Surabaya at 1 month Desember 2012 – 10 February 2013. The sample of the study15 patients with post-op trepanation head trauma. Sampling was done by purposive sampling technique. The variables of this study is the head-up 300 in patients post-op trepanation head trauma and cerebral perfusion. The results showed that the average MAP was100 mmHg and average GCS was 12.4. Based on the test paired t-test with significance level α=0.005 obtained P= 0.000 means there is influence the effectiveness of the head-up 300 against cerebral. Perfusionin patients with post-op trepanation after 8 hours. Head up to 300 can improve cerebral perfusion in patients with head trauma post op trepanation. This research needs to be recommended to the health practitioner, specializing in nursing to provide ahead-up position 300 to increase cerebral perfusion. Keywords: Flat Position, Head Up 300, Post Op Trepanation Head Trauma and Cerebral Perfusion.

Cerebral blood flow and cerebrovascular reactivity correlate with severity of motor symptoms in Parkinson's disease.

Background:Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is mainly characterized by movement dysfunction. Neurovascular unit (NVU) disruption has been proposed to be involved in the disease, but its role in PD neurodegenerative mechanisms is still unclear. The aim of this study was to investigate cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) within the regions belonging to the motor network, in patients with mild to moderate stages of PD.Methods:Twenty-eight PD patients (66.6 ± 8.6 years, 22 males, median [interquartile range, IQR] Hoehn & Yahr = 1.5 [1–1.9]) and 32 age- and sex-matched healthy controls (HCs) were scanned with arterial spin labeling (ASL) magnetic resonance imaging (MRI) for CBF assessment. ASL MRI was also acquired in hypercapnic conditions to induce vasodilation and subsequently allow for CVR measurement in a subgroup of 13 PD patients and 13 HCs. Median CBF and CVR were extracted from cortical and subcortical regions belonging to the motor network and compared between PD patients and HCs. In addition, the correlation between these parameters and the severity of PD motor symptoms [quantified with Unified Parkinson’s Disease Rating Scale part III (UPDRS III)] was assessed. The false discovery rate (FDR) method was used to correct for multiple comparisons.Results:No significant differences in terms of CBF and CVR were found between PD patients and HCs. Positive significant correlations were observed between CBF and UPDRS III within the precentral gyrus, postcentral gyrus, supplementary motor area, striatum, pallidum, thalamus, red nucleus, and substantia nigra (pFDR < 0.05). Conversely, significant negative correlation between CVR and UPDRS III was found in the corpus striatum (pFDR < 0.05).Conclusion:CBF and CVR assessment provides information about NVU integrity in an indirect and noninvasive way. Our findings support the hypothesis of NVU involvement at the mild to moderate stages of PD, suggesting that CBF and CVR within the motor network might be used as either diagnostic or prognostic markers for PD.

Neuromuscular blockade of atracurium in permissive hypercapnic versus normocapnic swine undergoing laparoscopy.

Neuromuscular blocking agents (NMBAs) are commonly used in experimental laparoscopy in swine undergoing carbon dioxide pneumoperitoneum. Hypercapnia may be present and may prolong NMBAs’ pharmacologic activity. The aim of this study is to evaluate the effect of permissive hypercapnia on the neuromuscular blockade of atracurium in swine. Six Large White swine weighing 30.5 ± 1.6 kg were sedated with intramuscular ketamine and medetomidine, after which anaesthesia was induced with propofol and maintained with sevoflurane. Atracurium 0.4 mg/kg was administered intravenously and the neuromuscular block monitored by acceleromyography during normocapnic and hypercapnic conditions (PaCO2 range 35–45 mmHg and 60–70 mmHg, respectively). Onset time and time to reach a train of four ratio (TOFR) of 0.7 and 0.9 were recorded. Cardiorespiratory parameters, electrolytes and acid-base status were measured under both conditions. Onset time was similar between the two conditions. Time to reach a TOFR of 0.7 and 0.9 (duration of the neuromuscular block) was longer in hypercapnic compared to normocapnic animals being 1325 ± 300 vs 855 ±111 (p = 0.002) and 1823 ± 434 vs 1218 ± 210 seconds (p = 0.005), respectively. Three hypercapnic swine had a TOF count of 2 and 1 instead of a count of 4 with fade. Permissive hypercapnia was associated with a decrease in pH from 7.444 ± 0.039 to 7.257 ± 0.025 (p < 0.001). No differences were observed for heart rate, end-tidal concentration of sevoflurane, body temperature and arterial haemoglobin saturation. Nonetheless, hypercapnic swine had a statistically significant increase in mean arterial pressure (p = 0.020) and plasma potassium concentration (p = 0.003). The values of PaCO2 achieved during hypercapnia were well tolerated in swine undergoing CO2 pneumoperitoneum for laparoscopy. Permissive hypercapnia increased the duration of the atracurium effect and caused an increase in the intensity of the neuromuscular block in few swine.

PLASMA ERYTHROPOIETIN CONCENTRATION DETERMINE THE CAROTID BODY CHEMOSENSITIVITY TO HYPOXIA AND HYPERCAPNIA IN RATS

We tested the hypothesis that Erythropoietin (Epo) have an impact in the modulation of carotid body (CB) chemoreceptors in response to hypoxia and hypercapnia. To study this subject, we used isolated and perfused ex vivo CB preparations from adult male Sprague Dawley rats. Prior evaluation of the carotid sinus nerve activity (CSNA ‐ throughout a suction glass electrode encircling and sealing the junction of the carotid body and the carotid sinus nerve), preparations were incubated for 1h with (or without) Epo at different concentrations. Then CBs were exposed to hypoxic and hypercapnic conditions. Normoxic baseline activity was not affected by any tested Epo concentration. However, under hypoxia and hypercapnia, Epo doses lower than 0.5U/ml increased the CSNA (by almost 40%), Epo doses higher than 0.5U/ml gradually decreased the CSNA in hypoxic and hypercapnic condition. Complete inhibition of CSNA was reached when preparations were incubated with 2U/ml of Epo concentration. Keeping in mind that nitric oxide (NO) in CB is an inhibitory messenger and that Epo in combination with low oxygen tension increase the endothelial capacity to produce NO, preparations were incubated at the same time with Epo (at the inhibitory concentration of 1 U/ml) and NO inhibitors, 400 μM L‐NAME (Nitric synthase inhibitor) or 100 μM 7NI (specific neuronal Nitric oxide synthase inhibitor). Our results showed that inhibition of NO (with L‐NAME and 7NI) fully restored the hypoxic CSNA. Similar results were found by exposing CB preparations to hypercapnic conditions. Accordingly, to these findings, immunohistochemistry studies showed a dense staining of Epo receptors (EpoR) in the carotid bodies, apparently localized within islets of chemosensitive cells. In summary, our results strongly suggest that the plasma Epo concentration determines the CB chemo‐response to hypoxic and hypercapnic conditions. These novel findings are relevant to better understand respiratory disorders, including those occurring at high altitude.Support or Funding InformationCIHR, Région Rhône Alpes and consulat de France in QuébecThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects on Breathing and the CO2 Chemoreflex of 5‐HT and NK‐1 Receptor Antagonists in the Retrotrapezoid Nucleus (RTN)

Serotonin (5‐HT) and Substance P, typically increase the excitability of neurons within the neural network controlling breathing through G protein‐coupled receptors. These neuromodulators also stimulate pH/CO2 sensitive Phox2b‐expressing (Phox2b+) neurons in the retrotrapezoid nucleus (RTN), but their role in supporting the ventilatory CO2 chemoreflex within the RTN has not been tested in vivo. We hypothesize that unilateral antagonism in the RTN of 5‐HT and/or NK‐1 receptors will attenuate the ventilatory CO2 chemoreflex. To test this hypothesis, 8 week old male Sprague Dawley rats were chronically implanted with guide cannula unilaterally using stereotaxic coordinates previously published (Dias et al., 2008). After 7 or more days of recovery, microdialysis probes were inserted into the guide cannula for dialysis of mCSF alone followed by mCSF mixed with individual or a cocktail of antagonists to 5‐HT7 receptors (SB 269970 (100 μM)), 5‐HT2A receptors (MDL 11,939 (20 μM)) and/or NK‐1 receptors (SR 140333 (40 μM)) while measuring breathing in room air (35 min) and during a 7% CO2 challenge (10 min) before and during drug dialysis. We found that SB 269970 consistently reduced hypercapnic breathing frequency (−9 ± 2%, n=3) compared to mCSF alone, and had mixed effects on eupneic breathing and hypercapnic tidal volume. MDL‐11939 consistently reduced eupneic breathing frequency (−7 ± 0.4%, n=3) and hypercapnic tidal volume (−17 ± 0.8%, n=3) compared to mCSF alone, but had mixed effects on eupneic tidal volume and hypercapnic breathing frequency. In addition, a cocktail of all antagonists consistently increased eupneic breathing frequency (+14%, n=2) and decreased hypercapnic breathing frequency (−7 ± 0.4%, n=2) compared to mCSF alone. These preliminary data suggest 5‐HT and Substance P within the RTN may modulate breathing at rest and during hypercapnic conditions in vivo.Support or Funding InformationThis work was supported by NIH HL122358.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Ventilatory Response to Muscle Metaboreflex Activation During Concurrent Hypercapnia is Attenuated by Local Muscle Training

Increased ventilation during post‐exercise circulatory occlusion (PECO) with concurrent hypercapnia suggests a synergistic interaction between muscle metaboreflex activation and chemoreflex stimulation. The exercise pressor reflex (EPR) response to contraction of a human calf muscle and subsequent PECO can be attenuated by training, indicating a decreased activation of muscle metaboreceptive afferents driving the EPR. We hypothesised that 6 weeks of one legged calf raise training would attenuate metaboreceptor activity, the EPR and if these afferents provide a drive to breathe, the ventilatory response seen during PECO when combined with mild hypercapnia. In the contralateral limb there would be no effect on muscle afferent input to the cardiovascular or respiratory control systems so no change in EPR or breathing would be expected during PECO.Eleven male subjects aged 19.5 ± 0.8 years (mean±SD) gave informed consent to participate in the study, approved by the local ethics committee. A standardized test of the cardiovascular and respiratory responses to isometric contraction of the calf muscle at 50% of maximum voluntary force (MVC) for 2 min was followed by 3 min of PECO. In random order left and right legs were tested separately under two conditions, 1) breathing room air 2) hypercapnia, 5% CO2 above end tidal level. A dynamic end tidal forcing system controlled the inspired gas composition and monitored ventilation. Heart rate (HR) and blood pressure (MAP) were measured by ECG and Portapres respectively. Right leg training consisted of 120 calf raises to maximum height in 4 sets of 30, one heel raise and lower per second, one minute rest between sets. Whenever 4 sets could be achieved loading of 10%, then increments of 5% body mass was added. After 6 weeks of training the initial tests were repeated.MVC did not change after training in either leg. During exercise of the trained leg during hypercapnia, average MAP rise from baseline was reduced from 18.1± 1.4, to 15.6±1.4 mmHg (mean±SEM), p&lt;0.05 after, training. Ventilation change from the hypercapnic baseline was also reduced from 17.5± 2.8 to 12.1±2.6 l.min−1, p&lt;0.05 after training.Table 1 shows the data from each leg in the PECO phase of the trials, performed before and after the training. In the room air and hypercapnia trials, the EPR was significantly reduced from control values in the trained leg. The increase in ventilation from baseline was reduced, by ~45%, in the trained limb during the hypercapnia trial. There were no alterations in the cardiovascular or ventilatory responses to PECO, during hypercapnia or room air breathing trials in the untrained limb, ruling out any central or peripheral adaptation in this leg, induced by the training period. In the trained leg the MAP data shows clear evidence of a decrease in the EPR after training, indicating reduced muscle metaboreflex activation during PECO. This is despite generating the same force‐time integral during the exercise period as before training. We conclude that in the trained limb the marked decrease in ventilation during PECO in the hypercapnia condition must be due to a decreased drive to breathe arising from metabosensitive muscle afferents.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cerebrovascular Control After Cardiac Rehabilitation in Ischemic Heart Disease Patients

In this study we evaluate the impact of ischemic heart disease (IHD) and cardiac rehabilitation (CR) on cerebrovascular control and peripheral vascular health. Patients with IHD are at greater risk for stroke, a risk determined in part by cerebrovasoreactivity tests (i.e., dilation or constriction to a known stimulus). Exercise provides cerebrovascular health benefits in the aging population; yet, effects of IHD and CR (exercise) on cerebrovascular health indicators and cerebral blood flow control are not understood. We explored cerebrovascular control (i.e., vasoreactivity and autoregulation), peripheral vascular health, brain volume, and white matter hyperintensities (WMH) in a group of healthy adults (CTL), and patients with IHD after cardiac event (pre‐CR) and following 6 months CR (post‐CR) comprised of 2–3 sessions/week of 30 minutes moderate intensity aerobic exercise and 30 minutes of resistance training. In 23 participants (CTL: 11, IHD: 12; age range: 40–75 years), we measured changes in cross‐sectional area (ΔCSA) divided by changes in end‐tidal CO2 (ΔPetCO2: CTL: 2.3±1.2, pre‐CR: 4.1±3.2, post‐CR: 5.2±2.2 mmHg)] during hypercapnic (5% CO2, 95% oxygen; ADInstruments) conditions using a 3 Tesla (Siemens) scanner and T1‐weighted pulse sequence (0.7 mm isotropic). Vasoreactivity was calculated for the basilar (BA), left (L) and right (R) internal carotid (ICA), anterior (ACA), middle (MCA), and posterior cerebral arteries (PCA) using OsiriX software. Autoregulation of the MCA was assessed by measuring relative changes in MCA flow velocity with respect to changes in mean arterial pressure during a sit‐to‐stand task, quantified by rate of regulation (ROR). Peripheral vascular health metrics included brachial artery flow‐mediated dilation (FMD; %) and common carotid artery (CCA) intima media thickness (mm) using duplex ultrasound. Compared to CTL, those with IHD had lower CSA reactivity (mm/mmHg; mean±SD; p&lt;0.05) in the BA (CTL: 0.74±0.73, pre‐CR: 0.29±0.29, post‐CR: 0.14±0.24), LICA (CTL: 1.1±0.86, pre‐CR: 0.93±1.03, post‐CR: 0.42±0.51), RICA (CTL: 0.93±0.71, pre‐CR: 0.48±0.35, post‐CR: 0.27±0.34), LMCA (CTL: 0.67±0.53, pre‐CR: 0.37±0.48, post‐CR: 0.14±0.12), and RMCA (CTL: 0.93±0.95, pre‐CR: 0.33±0.37, post‐CR: 0.29±0.33), which were not improved with CR. Compared to CTL, those with IHD had greater CCA IMT (CTL: 0.43±0.05, pre‐CR: 0.58±0.09, post‐CR: 0.59±0.07) which was not improved with CR, as well as lower ROR (CTL: 0.18±0.02, pre‐CR: 0.14±0.03, post‐CR: 0.16±0.03) and lower FMD (CTL: 9.1±4.3, pre‐CR: 4.7±2.3, post‐CR: 6.1±1.3; p&lt;0.05) which were improved with CR. Finally, brain volume and white matter lesions were similar across groups. Therefore, compared to healthy individuals, the IHD patients exhibited impaired cerebrovascular control and peripheral endothelial function. Peripheral vascular health, and cerebrovascular autoregulation, were improved with 6 months of CR in these IHD patients.Support or Funding InformationCanadian Institute of Health Research (201503MOP‐342412‐MOV‐CEEA).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of hypercapnia on the swallow‐breathing relationship in cats

Swallow‐breathing coordination is critical for maintaining a clear airway during the act of swallowing. Swallows can occur during all phases of breathing, however, they are primarily initiated during expiration. The interaction between central pattern generators for swallowing and breathing contribute to this phase preference. While hypercapnia has known effects on the breathing central pattern generator, the effects of elevated CO2 on swallow‐breathing coordination are unknown. We examined the influence of hypercapnia on swallow‐breathing phase preference in the cat. Swallowing was induced in anesthetized spontaneously breathing cats by injection of water into the oropharynx and experiments were conducted under conditions of room air, 5% CO2, or 10% CO2. Electromyogram activity was measured using bipolar electrodes inserted into laryngeal and pharyngeal muscles (mylohyoid, geniohyoid, thyrohyoid, and thyropharyngeus), parasternal muscles and costal diaphragm. In cats breathing room air, 71% of swallows occurred during expiration (E), 12% during inspiration (I), 10% during the transition from inspiration to expiration (I to E), and 7% during the transition from expiration to inspiration (E to I). Under hypercapnic conditions swallows occurred more frequently during inspiration with 80% (5% CO2) and 68% (10% CO2) occurring during either the I or the E to I phases of breathing, and 16% (5% CO2) and 25% (10% CO2) occurring during expiration. These preliminary results suggest hypercapnia may affect swallow‐breathing coordination by causing the initiation of swallow to occur in more inspiratory phases (I and E to I).Support or Funding InformationSupported by R00‐HL 111215, NIH HL 103415, and 1OT20D001983.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Brainstem catecholaminergic neurones and breathing control during postnatal development in male and female rats

The brainstem catecholaminergic (CA) modulation on ventilation changes with development. We determined the role of the brainstem CA system in ventilatory control under normocapnic and hypercapnic conditions during different phases of development [postnatal day (P)7-8, P14-15 and P20-21] in male and female Wistar rats. Brainstem CA neurones produce a tonic inhibitory drive that affects breathing frequency in P7-8 rats and provide an inhibitory drive during hypercapnic conditions in both males and females at P7-8 and P14-15. In pre-pubertal rats, brainstem CA neurones become excitatory for the CO2 ventilatory response in males but remain inhibitory in females. Diseases such as sudden infant death syndrome, congenital central hypoventilation syndrome and Rett syndrome have been associated with abnormalities in the functioning of CA neurones; therefore, the results of the present study contribute to a better understanding of this system. The respiratory network undergoes significant development during the postnatal phase, including the maturation of the catecholaminergic (CA) system. However, postnatal development of this network and its effect on the control of pulmonary ventilation ( ) is not fully understood. We investigated the involvement of brainstem CA neurones in respiratory control during postnatal development [postnatal day (P)7-8, P14-15 and P20-21], in male and female rats, through chemical injury with conjugated saporin anti-dopamine β-hydroxylase (DβH-SAP). Thus, DβH-SAP (420ngμL-1 ), saporin (SAP) or phosphate buffered solution (PBS) was injected into the fourth ventricle of neonatal Wistar rats of both sexes. and oxygen consumption were recorded 1week after the injections in unanaesthetized neonatal and juvenile rats during room air and hypercapnia. The resting ventilation was higher in both male and female P7-8 lesioned rats by 33%, with a decrease in respiratory variability being observed in males. The hypercapnic ventilatory response (HCVR) was altered in male and female lesioned rats at all postnatal ages. At P7-8, the HCVR for males and females was increased by 37% and 30%, respectively. For both sexes at P14-15 rats, the increase in during hypercapnia was 37% higher for lesioned rats. A sex-specific difference in HCRV was observed at P20-21, with lesioned males showing a 33% decrease, and lesioned females showing an increase of 33%. We conclude that brainstem CA neurones exert a tonic inhibitory effect on in the early postnatal days of the life of a rat, increase variability in P7-8 males and modulate HCRV during the postnatal phase.

Central monoaminergic systems sensitivity to acute hypoxia with hypercapnia changes after the maintenance under the long-term social isolation

The experiments were performed in male albino outbred mice kept in a group and under the conditions of long-term social isolation. The changes in the monoaminergic systems of the left and right hemispheres of the brain after acute hypoxia with hypercapnia have been studied. The levels of dopamine (DA), serotonin (5-HT) and their metabolites - dioxyphenylacetic (DOPAC), homovanillic (HVA), and 5-hydroxyindoleacetic (5-HIAA) acids - were determined by HPLC in the cerebral cortex, hippocampus and striatum of the right and left sides of the brain. In the control mice kept both in the group and under the conditions of social isolation, a higher content of DA in the cortex of the left hemisphere has been found. In the other brain structures the monoamine content was symmetric. In the cerebral cortex of the mice in the group, acute hypoxia with hypercapnia led to a right-sided increase in the DA and 5HT levels. At the same time, the DOPAC content decreased in the left cortex. In mice in the group, under the hypoxia with hypercapnia conditions, the DA level in the left hippocampus increased. In the striatum, the content of monoamines and their metabolites did not change significantly. In animals kept for a long time under the conditions of social isolation, hypoxia with hypercapnia no statistically significant changes in the monoamines and their metabolites levels were found. It has been concluded that the preliminary maintenance under the conditions of prolonged social isolation changes the reaction of central monoaminergic systems to acute hypoxia with hypercapnia.

Interdependent feedback regulation of breathing by the carotid bodies and the retrotrapezoid nucleus.

The retrotrapezoid nucleus (RTN) regulates breathing in a CO2 - and state-dependent manner. RTN neurons are glutamatergic and innervate principally the respiratory pattern generator; they regulate multiple aspects of breathing, including active expiration, and maintain breathing automaticity during non-REM sleep. RTN neurons encode arterial /pH via cell-autonomous and paracrine mechanisms, and via input from other CO2 -responsive neurons. In short, RTN neurons are a pivotal structure for breathing automaticity and arterial homeostasis. The carotid bodies stimulate the respiratory pattern generator directly and indirectly by activating RTN via a neuronal projection originating within the solitary tract nucleus. The indirect pathway operates under normo- or hypercapnic conditions; under respiratory alkalosis (e.g. hypoxia) RTN neurons are silent and the excitatory input from the carotid bodies is suppressed. Also, silencing RTN neurons optogenetically quickly triggers a compensatory increase in carotid body activity. Thus, in conscious mammals, breathing is subject to a dual and interdependent feedback regulation by chemoreceptors. Depending on the circumstance, the activity of the carotid bodies and that of RTN vary in the same or the opposite directions, producing additive or countervailing effects on breathing. These interactions are mediated either via changes in blood gases or by brainstem neuronal connections, but their ultimate effect is invariably to minimize arterial fluctuations. We discuss the potential relevance of this dual chemoreceptor feedback to cardiorespiratory abnormalities present in diseases in which the carotid bodies are hyperactive at rest, e.g. essential hypertension, obstructive sleep apnoea and heart failure.

Quantitative Measurement of Oxygen Extraction Fraction (OEF) Using Respiratory Modulated Perfusion MRI

Background: Measurement of oxygen consumption can give useful information of brain functionality in health and disease. To have a better understanding of normal physiology in all conditions (rest or functional tasks), development of accurate brain oxygen mapping is essential. This mapping could also be a great help in managing pathological conditions with disturbance in oxygen supply. One of the most important hemodynamic parameters of the brain is oxygen extraction fraction (OEF). By development of blood oxygen level dependent magnetic resonance imaging (BOLD MRI) in imaging, several methods have been proposed for measuring this parameter. The latest methods are mostly based on hypercapnic and hyperoxic stimulus. Objectives: Here, we presented a new method with hypercapnic and hyperoxic stimulus and using BOLD and dynamic susceptibility contrast (DSC) perfusion imaging instead of arterial spin labelling (ASL). Materials and Methods: A 3T Siemens Trio Tim Scanner was used for imaging five patients (three males and two females) who were recruited for this experiment. Four set of T1 data, BOLD data and two DSC-perfusions (two injections) were applied to each subject. Gas manipulation was applied while acquiring BOLD data and one of the DSC-perfusion was done in hyperoxic condition. Gas manipulation was a combination of hypercapnic, hyperoxic and normoxic conditions in a total of 13 minutes. The DSC data was analyzed using PMA (ASIST) software to calculate cerebral blood flow (CBF) and using its results with the BOLD data, OEF was calculated by MATLAB coding. All preprocessing was done with the SPM12 (MATLAB). Results: Comparable results were acquired for OEF with previous studies. The mean value of estimated OEF for gray matter (GM), white matter (WM) and whole brain is 0.46, 0.37, and 0.44, respectively which are within the expected range of normal condition. Conclusion: As the proposed method for OEF measurement uses a combination of hyperoxic and hypercapnic stimulus with BOLD and DSC-perfusion imaging, it could be considered the most available one in all MRI scanners and being a voxel wise method, it could give OEF value for any requested ROI.

The combined effects of acidification and hypoxia on pH and aragonite saturation in the coastal waters of the California current ecosystem and the northern Gulf of Mexico

Inorganic carbon chemistry data from the surface and subsurface waters of the West Coast of North America have been compared with similar data from the northern Gulf of Mexico to demonstrate how future changes in CO2 emissions will affect chemical changes in coastal waters affected by respiration-induced hypoxia ([O2] ≤ ~ 60µmolkg−1). In surface waters, the percentage change in the carbon parameters due to increasing CO2 emissions are very similar for both regions even though the absolute decrease in aragonite saturation is much higher in the warmer waters of the Gulf of Mexico. However, in subsurface waters the changes are enhanced due to differences in the initial oxygen concentration and the changes in the buffer capacity (i.e., increasing Revelle Factor) with increasing respiration from the oxidation of organic matter, with the largest impacts on pH and CO2 partial pressure (pCO2) occurring in the colder West Coast waters. As anthropogenic CO2 concentrations begin to build up in subsurface waters, increased atmospheric CO2 will expose organisms to hypercapnic conditions (pCO2 >1000 µatm) within subsurface depths. Since the maintenance of the extracellular pH appears as the first line of defense against external stresses, many biological response studies have been focused on pCO2-induced hypercapnia. The extent of subsurface exposure will occur sooner and be more widespread in colder waters due to their capacity to hold more dissolved oxygen and the accompanying weaker acid-base buffer capacity. Under present conditions, organisms in the West Coast are exposed to hypercapnic conditions when oxygen concentrations are near 100µmolkg−1 but will experience hypercapnia at oxygen concentrations of 260µmolkg−1 by year 2100 under the highest elevated-CO2 conditions. Hypercapnia does not occur at present in the Gulf of Mexico but will occur at oxygen concentrations of 170µmolkg−1 by the end of the century under similar conditions. The aragonite saturation horizon is currently above the hypoxic zone in the West Coast. With increasing atmospheric CO2, it is expected to shoal up close to surface waters under the IPCC Representative Concentration Pathway (RCP) 8.5 in West Coast waters, while aragonite saturation state will exhibit steeper gradients in the Gulf of Mexico. This study demonstrates how different biological thresholds (e.g., hypoxia, CaCO3 undersaturation, hypercapnia) will vary asymmetrically because of local initial conditions that are affected differently with increasing atmospheric CO2. The direction of change in amplitude of hypercapnia will be similar in both ecosystems, exposing both biological communities from the West Coast and Gulf of Mexico to intensification of stressful conditions. However, the region of lower Revelle factors (i.e., the Gulf of Mexico), currently provides an adequate refuge habitat that might no longer be the case under the most severe RCP scenarios.

Interactive effects of increased temperature, pCO2 and the synthetic progestin levonorgestrel on the fitness and breeding of the amphipod Gammarus locusta.

Given the lack of knowledge regarding climate change-chemical exposure interactions, it is vital to evaluate how these two drivers jointly impact aquatic species. Thus, for the first time, we aimed at investigating the combined effects of increased temperature, pCO2 and the synthetic progestin levonorgestrel on survival, growth, consumption rate and reproduction of the amphipod Gammarus locusta. For that, a full factorial design manipulating temperature [ambient temperature and warming (+4°C)], pCO2 [normocapnia and hypercapnia (Δ pH 0.5 units)] and the progestin levonorgestrel (LNG: L1 - 10ngLL-1 and L2 - 1000ngLL-1, control - no progestin and solvent control - vehicle ethanol (0.01%)) was implemented for 21 days. G.locusta was strongly negatively affected by warming, experiencing higher mortality rates (50-80%) than in any other treatments. Instead, growth rates were significantly affected by interactions of LNG with temperature and pCO2. It was observed, in the short-term (7d) that under ambient temperature (18°C) and hypercapnic conditions (pH 7.6), the LNG presence promoted the amphipod's growth, while in the medium-term (21d) this response was not observed. Relative consumption rates (RCRs), during the first week were higher than in the third week. Furthermore, in the first week, RCRs were negatively affected by higher temperature while in the third week, RCRs were negatively affected by acidification. Furthermore, it was observed a negative effect of higher temperature and acidification on G.locusta fecundity, contrarily to LNG. Concluding, the impact of increased temperature and pCO2 was clearly more adverse for the species than exposure to the synthetic progestin, however, some interactions between the progestin and the climate factors were observed. Thus, in a future scenario of global change, the presence of LNG (and other progestins alike) may modulate to a certain level the effects of climate drivers (and vice-versa) on the gammarids fitness and reproduction.

Уровень физического состояния здоровья и физической подготовленности организма борцов – ветеранов спорта

Oleksiy Goncharov, Larysa Ruban & Kostiantyn Ananchenko Purpose: study and an assessment of the physical state of health and the degree of physical fitness of the organism among active veteran wrestlers. Material & Methods: participants: 16 active veteran athletes, 7 of them judoka and 9 sambo wrestlers aged 36–45. Sports qualification of athletes: MS – 10 people, MSIC – 6 people. The stability of the organism to the conditions of hypoxia and hypercapnia was assessed by the results of the Stange and Genci tests. To determine the statistical balancing, the Bondarevsky trial was used. The degree of physical readiness was evaluated by the results of the distance traveled on the treadmill of Kettler, comparing it with the Cooper table. To assess the level of physical state, the formula was used by E. A. Pirogova. Results: investigation determined that the actions of the wrestlers – sports veterans of the body's resistance to the conditions of hypoxia and hypercapnia, as well as the indicator VC indices correspond young people. Indicators of statistical balancing among the acting veterans of judoists and sambo wrestlers corresponded to those of 20–30-year-old people. Level of physical condition (LPC) of health in 71,4% of veteran-judoists at the average level and only 28,6% is of a high level. Sambo veterans observed the following: 44,4% of sportsmen of the LPC are above the average; 33,3% have an average level of physical health; in 11,1% of athletes the average LPC and 11,1% of the judo veterans have indicators corresponding to the level below the average. Conclusion: conducted step-by-step medical and pedagogical control allowed to reveal some violations of the adaptive mechanisms of the cardiovascular system, which once again confirms the possibility of using the data of heart rate, blood pressure, Cooper's test for studying and analyzing the physical state of health and the degree of physical preparedness, as well as forecasting the health status of veterans sports.

Increased putamen hypercapnic vasoreactivity in levodopa-induced dyskinesia

In a rodent model of Parkinson's disease (PD), levodopa-induced involuntary movements have been linked to striatal angiogenesis - a process that is difficult to document in living human subjects. Angiogenesis can be accompanied by localized increases in cerebral blood flow (CBF) responses to hypercapnia. We therefore explored the possibility that, in the absence of levodopa, local hypercapnic CBF responses are abnormally increased in PD patients with levodopa-induced dyskinesias (LID) but not in their nondyskinetic (NLID) counterparts. We used H215O PET to scan 24 unmedicated PD subjects (12 LID and 12 NLID) and 12 matched healthy subjects in the rest state under normocapnic and hypercapnic conditions. Hypercapnic CBF responses were compared to corresponding levodopa responses from the same subjects. Group differences in hypercapnic vasoreactivity were significant only in the posterior putamen, with greater CBF responses in LID subjects compared with the other subjects. Hypercapnic and levodopa-mediated CBF responses measured in this region exhibited distinct associations with disease severity: the former correlated with off-state motor disability ratings but not symptom duration, whereas the latter correlated with symptom duration but not motor disability. These are the first in vivo human findings linking LID to microvascular changes in the basal ganglia.

Impaired chemosensory control of breathing after depletion of bulbospinal catecholaminergic neurons in rats.

Bulbospinal catecholaminergic neurons located in the rostral aspect of the ventrolateral medulla (C1 neurons) or within the ventrolateral pons (A5 neurons) are involved in the regulation of blood pressure and sympathetic outflow. A stimulus that commonly activates the C1 or A5 neurons is hypoxia, which is also involved in breathing activation. Although pharmacological and optogenetic evidence suggests that catecholaminergic neurons also regulate breathing, a specific contribution of the bulbospinal neurons to respiratory control has not been demonstrated. Therefore, in the present study, we evaluated whether the loss of bulbospinal catecholaminergic C1 and A5 cells affects cardiorespiratory control during resting, hypoxic (8% O2), and hypercapnic (7% CO2) conditions in unanesthetized rats. Thoracic spinal cord (T4-T8) injections of the immunotoxin anti-dopamine β-hydroxylase-saporin (anti-DβH-SAP-2.4ng/100nl) and the retrograde tracer Fluor-Gold or ventrolateral pontine injections of 6-OHDA were performed in adult male Wistar rats (250-280g, N=7-9/group). Anti-DβH-SAP or 6-OHDA eliminated most bulbospinal C1 and A5 neurons or A5 neurons, respectively. Serotonergic neurons and astrocytes were spared. Depletion of the bulbospinal catecholaminergic cells did not change cardiorespiratory variables under resting condition, but it did affect the response to hypoxia and hypercapnia. Specifically, the increase in the ventilation, the number of sighs, and the tachycardia were reduced, but the MAP increased during hypoxia in anti-DβH-SAP-treated rats. Our data reveal that the bulbospinal catecholaminergic neurons (A5 and C1) facilitate the ventilatory reflex to hypoxia and hypercapnia.

Emergency Department Blood Gas Utilization and Changes in Ventilator Settings.

Mechanically ventilated patients increasingly spend hours in emergency department beds before ICU admission. This study evaluated the performance of blood gases in mechanically ventilated subjects in the emergency department and subsequent changes to mechanical ventilation settings. This was a multi-center, prospective, observational study of subjects ventilated in the emergency department, conducted at 3 academic emergency departments from July 2011 to March 2013. We measured the rate of arterial blood gas (ABG) and venous blood gas (VBG) analysis, and we assessed the associations between the conditions of hypoxemia, hyperoxia, hypercapnia, or acidemia and changes to mechanical ventilator settings. Of 292 ventilated subjects, 17.1% did not have a blood gas sent in the emergency department. Ventilator changes were made significantly more frequently for subjects who had an ABG as the initial blood gas sent in the emergency department (odds ratio 2.70, 95% CI 1.46-4.99, P = .002). However, findings of hypoxemia, hyperoxia, hypercapnia, or acidemia were not correlated with ventilator adjustments. In this prospective observational study of subjects mechanically ventilated in the emergency department, the majority had a blood gas checked while in the emergency department. While ABGs were associated with having changes made to ventilator settings in the emergency department, clinical findings of hypoxemia, hyperoxia, hypercapnia, and acidemia were not. Inattention to blood gas results may lead to missed opportunities in guiding ventilator changes in the emergency department.

Metabolic response and thermal tolerance of green abalone juveniles (Haliotis fulgens: Gastropoda) under acute hypoxia and hypercapnia

With ongoing climate change, rising ocean temperature is usually accompanied by falling oxygen levels (hypoxia) and increasing CO2 concentration (hypercapnia). Both drivers may impose constraints on physiological mechanisms that define thermal limits resulting in increased vulnerability towards warming in marine ectotherms. The present study aimed to detect differences in thermal tolerance by investigating the underlying metabolic responses in the green abalone (Haliotis fulgens) under conditions of hypoxia and hypercapnia. Juvenile abalones were exposed to a temperature ramp (+3°Cday−1) under hypoxia (50% air saturation) and hypercapnia (~1000μatm pCO2), both individually and in combination. Impacts on energy metabolism were assessed by analyzing whole animal respiration rates and metabolic profiles of gills and hepatopancreas via 1H NMR spectroscopy. While hypercapnia had a minor impact on the results of the temperature treatment, hypoxia strongly increased the vulnerability to warming, indicated by respiration rates falling below values expected from an exponential increase and by the onset of anaerobic metabolism suggesting a downward shift of the upper critical temperature. Warming under combined hypoxia and hypercapnia elicited a severe change in metabolism involving a strong accumulation of amino acids, osmolytes and anaerobic end products at intermediate temperatures, followed by declining concentrations at warmer temperatures. This matched the limited capacity to increase metabolic rate, loss of attachment and mortality observed under these conditions suggesting a strong narrowing of the thermal window. In all cases, the accumulation of free amino acids identified proteins as a significant energy source during warming stress.