Respiration in neonate sea turtles.

PubMed

Price, Edwin R; Paladino, Frank V; Strohl, Kingman P; Santidrián T, Pilar; Klann, Kenneth; Spotila, James R

2007-03-01

The pattern and control of respiration is virtually unknown in hatchling sea turtles. Using incubator-raised turtles, we measured oxygen consumption, frequency, tidal volume, and minute volume for leatherback (Dermochelys coriacea) and olive ridley (Lepidochelys olivacea) turtle hatchlings for the first six days after pipping. In addition, we tested the hatchlings' response to hypercapnic, hyperoxic, and hypoxic challenges over this time period. Hatchling sea turtles generally showed resting ventilation characteristics that are similar to those of adults: a single breath followed by a long respiratory pause, slow frequency, and high metabolic rate. With hypercapnic challenge, both species responded primarily by elevating respiratory frequency via a decrease in the non-ventilatory period. Leatherback resting tidal volume increased with age but otherwise, neither species' resting respiratory pattern nor response to gas challenge changed significantly over the first few days after hatching. At the time of nest emergence, sea turtles have achieved a respiratory pattern that is similar to that of actively diving adults.

Hypercapnic encephalopathy syndrome: a new frontier for non-invasive ventilation?

PubMed

Scala, Raffaele

2011-08-01

According to the classical international guidelines, non-invasive ventilation is contraindicated in hypercapnic encephalopathy syndrome (HES) due to the poor compliance to ventilatory treatment of confused/agitated patients and the risk of aspirative pneumonia related to lack of airways protection. As a matter of fact, conventional mechanical ventilation has been recommended as "golden standard" in these patients. However, up to now there are not controlled data that have demonstrated in HES the advantage of conventional mechanical ventilation vs non-invasive ventilation. In fact, patients with altered mental status have been systematically excluded from the randomised and controlled trials performed with non-invasive ventilation in hypercapnic acute respiratory failure. Recent studies have clearly demonstrated that an initial cautious NPPV trial in selected HES patients may be attempt as long as there are no other contraindications and the technique is provided by experienced caregivers in a closely monitored setting where ETI is always readily available. The purpose of this review is to report the physiologic rationale, the clinical feasibility and the still open questions about the careful use of non-invasive ventilation in HES as first-line ventilatory strategy in place of conventional mechanical ventilation via endotracheal intubation. Copyright © 2011 Elsevier Ltd. All rights reserved.

The effect of metabolic alkalosis on the ventilatory response in healthy subjects.

PubMed

Oppersma, E; Doorduin, J; van der Hoeven, J G; Veltink, P H; van Hees, H W H; Heunks, L M A

2018-02-01

Patients with acute respiratory failure may develop respiratory acidosis. Metabolic compensation by bicarbonate production or retention results in posthypercapnic alkalosis with an increased arterial bicarbonate concentration. The hypothesis of this study was that elevated plasma bicarbonate levels decrease respiratory drive and minute ventilation. In an intervention study in 10 healthy subjects the ventilatory response using a hypercapnic ventilatory response (HCVR) test was assessed, before and after administration of high dose sodium bicarbonate. Total dose of sodiumbicarbonate was 1000 ml 8.4% in 3 days. Plasma bicarbonate increased from 25.2 ± 2.2 to 29.2 ± 1.9 mmol/L. With increasing inspiratory CO 2 pressure during the HCVR test, RR, V t , Pdi, EAdi and V E increased. The clinical ratio ΔV E /ΔP et CO 2 remained unchanged, but Pdi, EAdi and V E were significantly lower after bicarbonate administration for similar levels of inspired CO 2 . This study demonstrates that in healthy subjects metabolic alkalosis decreases the neural respiratory drive and minute ventilation, as a response to inspiratory CO 2 . Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Antioxidants reverse depression of the hypoxic ventilatory response by acetazolamide in man.

PubMed

Teppema, Luc J; Bijl, Hans; Romberg, Raymonda R; Dahan, Albert

2006-05-01

The carbonic anhydrase inhibitor acetazolamide may have both inhibitory and stimulatory effects on breathing. In this placebo-controlled double-blind study we measured the effect of an intravenous dose (4 mg kg(-1)) of this agent on the acute isocapnic hypoxic ventilatory response in 16 healthy volunteers (haemoglobin oxygen saturation 83-85%) and examined whether its inhibitory effects on this response could be reversed by antioxidants (1 g ascorbic acid i.v. and 200 mg alpha-tocopherol p.o.). The subjects were randomly divided into an antioxidant (Aox) and placebo group. In the Aox group, acetazolamide reduced the mean normocapnic and hypercapnic hypoxic responses by 37% (P < 0.01) and 55% (P < 0.01), respectively, and abolished the O2-CO2 interaction, i.e. the increase in O2 sensitivity with rising Pco2. Antioxidants completely reversed this inhibiting effect on the normocapnic hypoxic response, while in hypercapnia the reversal was partial. In the placebo group, acetazolamide reduced the normo- and hypercapnic hypoxic responses by 33 and 47%, respectively (P < 0.01 versus control in both cases), and also abolished the O2-CO2 interaction. Placebo failed to reverse these inhibitory effects of acetazolamide in this group. We hypothesize that either an isoform of carbonic anhydrase may be involved in the regulation of the redox state in the carotid bodies or that acetazolamide and antioxidants exert independent effects on oxygen-sensing cells, in which both carbonic anhydrase and potassium channels may be involved. The novel findings of this study may have clinical implications, for example with regard to a combined use of acetazolamide and antioxidants at high altitude.

Antioxidants reverse depression of the hypoxic ventilatory response by acetazolamide in man

PubMed Central

Teppema, Luc J; Bijl, Hans; Romberg, Raymonda R; Dahan, Albert

2006-01-01

The carbonic anhydrase inhibitor acetazolamide may have both inhibitory and stimulatory effects on breathing. In this placebo-controlled double-blind study we measured the effect of an intravenous dose (4 mg kg−1) of this agent on the acute isocapnic hypoxic ventilatory response in 16 healthy volunteers (haemoglobin oxygen saturation 83–85%) and examined whether its inhibitory effects on this response could be reversed by antioxidants (1 g ascorbic acid i.v. and 200 mg α-tocopherol p.o.). The subjects were randomly divided into an antioxidant (Aox) and placebo group. In the Aox group, acetazolamide reduced the mean normocapnic and hypercapnic hypoxic responses by 37% (P < 0.01) and 55% (P < 0.01), respectively, and abolished the O2–CO2 interaction, i.e. the increase in O2 sensitivity with rising PCO2. Antioxidants completely reversed this inhibiting effect on the normocapnic hypoxic response, while in hypercapnia the reversal was partial. In the placebo group, acetazolamide reduced the normo- and hypercapnic hypoxic responses by 33 and 47%, respectively (P < 0.01 versus control in both cases), and also abolished the O2–CO2 interaction. Placebo failed to reverse these inhibitory effects of acetazolamide in this group. We hypothesize that either an isoform of carbonic anhydrase may be involved in the regulation of the redox state in the carotid bodies or that acetazolamide and antioxidants exert independent effects on oxygen-sensing cells, in which both carbonic anhydrase and potassium channels may be involved. The novel findings of this study may have clinical implications, for example with regard to a combined use of acetazolamide and antioxidants at high altitude. PMID:16439432

Exercise training effects on hypoxic and hypercapnic ventilatory responses in mice selected for increased voluntary wheel running.

PubMed

Kelly, Scott A; Rezende, Enrico L; Chappell, Mark A; Gomes, Fernando R; Kolb, Erik M; Malisch, Jessica L; Rhodes, Justin S; Mitchell, Gordon S; Garland, Theodore

2014-02-01

What is the central question of this study? We used experimental evolution to determine how selective breeding for high voluntary wheel running and exercise training (7-11 weeks) affect ventilatory chemoreflexes of laboratory mice at rest. What is the main finding and its importance? Selective breeding, although significantly affecting some traits, did not systematically alter ventilation across gas concentrations. As with most human studies, our findings support the idea that endurance training attenuates resting ventilation. However, little evidence was found for a correlation between ventilatory chemoreflexes and the amount of individual voluntary wheel running. We conclude that exercise 'training' alters respiratory behaviours, but these changes may not be necessary to achieve high levels of wheel running. Ventilatory control is affected by genetics, the environment and gene-environment and gene-gene interactions. Here, we used an experimental evolution approach to test whether 37 generations of selective breeding for high voluntary wheel running (genetic effects) and/or long-term (7-11 weeks) wheel access (training effects) alter acute respiratory behaviour of mice resting in normoxic, hypoxic and hypercapnic conditions. As the four replicate high-runner (HR) lines run much more than the four non-selected control (C) lines, we also examined whether the amount of exercise among individual mice was a quantitative predictor of ventilatory chemoreflexes at rest. Selective breeding and/or wheel access significantly affected several traits. In normoxia, HR mice tended to have lower mass-adjusted rates of oxygen consumption and carbon dioxide production. Chronic wheel access increased oxygen consumption and carbon dioxide production in both HR and C mice during hypercapnia. Breathing frequency and minute ventilation were significantly reduced by chronic wheel access in both HR and C mice during hypoxia. Selection history, while significantly affecting some traits, did not systematically alter ventilation across all gas concentrations. As with most human studies, our findings support the idea that endurance training (access to wheel running) attenuates resting ventilation. However, little evidence was found for a correlation at the level of the individual variation between ventilatory chemoreflexes and performance (amount of individual voluntary wheel running). We tentatively conclude that exercise 'training' alters respiratory behaviours, but these changes may not be necessary to achieve high levels of wheel running.

[Long-term non-invasive ventilation in chronic obstructive pulmonary disease patients].

PubMed

Schopfer, Léonore; Groenendijk, Lena; Janssens, Jean-Paul; Younossian, Alain Bigin; Vignaux, Laurence

2018-01-31

Non-invasive ventilation (NIV) is recognized as first line therapy in acute hypercapnic respiratory failure and chronic alveolar hypoventilation caused by several diseases (restrictive thoracic disorders, neuromuscular disease and obesity-hypoventilation syndrome). In Switzerland and other European countries, long-term NIV has also been applied in hypercapnic patients with chronic obstructive pulmonary disease (COPD). However, only recently has conclusive evidence showing benefits of long-term NIV become available. Long-term NIV in COPD has now shown its efficacy in many studies. However, despite these findings, indications, ventilatory settings and monitoring remain poorly known and topic of debate.

Effect of treatment with nasal continuous positive airway pressure on ventilatory response to hypoxia and hypercapnia in patients with sleep apnea syndrome.

PubMed

Spicuzza, Lucia; Bernardi, Luciano; Balsamo, Rossella; Ciancio, Nicola; Polosa, Riccardo; Di Maria, Giuseppe

2006-09-01

The increase in peripheral chemoreflex sensitivity in patients with obstructive sleep apnea (OSA) is associated with activation of autonomic nervous system and hemodynamic responses. Nasal CPAP (nCPAP) is an effective treatment for OSA, but little is known on its effect on chemoreflex sensitivity. To assess the effect of nCPAP treatment or placebo (sham nCPAP) on ventilatory control in patients with OSA. Sleep laboratory of Azienda Ospedaliera Garibaldi. Twenty-five patients with moderate-to-severe OSA. Patients were randomly assigned to either therapeutic nCPAP (use of optimal pressure, n = 15) or sham nCPAP (suboptimal pressure of 1 to 2 cm H2O, n = 10) in a double-blind fashion and treated for 1 month. A rebreathing test to assess ventilatory response to normocapnic hypoxia and normoxic hypercapnia was performed at basal condition and after 1 month of treatment. The use of therapeutic nCPAP or sham nCPAP did not affect daytime percentage of arterial oxygen saturation (SaO2%) or end-tidal P(CO2). The normocapnic hypoxic ventilatory response was reduced after 1 month of treatment with nCPAP (the slope was 1.08 +/- 0.02 L/min/SaO2% at basal condition and 0.53 +/- 0.07 L/min/SaO2% after 1 month of treatment, p = 0.008) [mean +/- SD], but not in patients treated with sham nCPAP (slope, 0.83 +/- 0.09 L/min/SaO2% and 0.85 +/- 0.19 L/min/SaO2% at basal condition and after 1 month, respectively). The normoxic hypercapnic ventilatory response remained unchanged after 1 month in both groups. No changes in ventilatory response to either hypoxia or hypercapnia were observed after a single night of nCPAP treatment. The ventilatory response to hypoxia is reduced during regular treatment, but not after short-term treatment, with nCPAP. Readjusted peripheral oxygen chemosensitivity during nCPAP treatment may be a side effect of both reduced sympathetic activity and increased baroreflex activity, or a possible continuous positive airway pressure-related mechanism leading to a reduced activation of autonomic nervous system per se.

Reduced suppression of CO2-induced ventilatory stimulation by endomorphins relative to morphine.

PubMed

Czapla, Marc A; Zadina, James E

2005-10-19

Opioids are among the most effective analgesics, but a major limitation for their therapeutic usefulness is their induction of respiratory depression. Endomorphin-1 (EM1), in contrast to several other mu opioids, exhibits a threshold for respiratory depression that is well above its threshold for analgesia. Its effect on sensitivity to CO(2), however, remains unknown. Minute ventilation (V(E)) in 2, 4, and 6% CO(2) was measured before and after systemic administration of EM1, endomorphin-2 (EM2), DAMGO, and morphine in the conscious rat. EM1 and EM2 attenuated the hypercapnic ventilatory response (HCVR) only in high doses, while DAMGO and morphine diminished the HCVR in much lower doses. The ventilatory effects of high doses of all 4 agonists were blocked by the mu-opioid antagonist naloxone (0.4 mg/kg i.v.), but not by the peripherally restricted mu-opioid antagonist, methyl-naloxone (0.4 mg/kg i.v.). It was concluded that the endomorphins attenuated the HCVR only in large doses, well beyond the analgesic threshold, and did so through a centrally mediated mu-opioid mechanism.

Ventilatory Responses to Hypercapnia during Wakefulness and Sleep in Obese Adolescents With and Without Obstructive Sleep Apnea Syndrome

PubMed Central

Yuan, Haibo; Pinto, Swaroop J.; Huang, Jingtao; McDonough, Joseph M.; Ward, Michelle B.; Lee, Yin N.; Bradford, Ruth M.; Gallagher, Paul R.; Shults, Justine; Konstantinopoulou, Sophia; Samuel, John M.; Katz, Eliot S.; Hua, Shucheng; Tapia, Ignacio E.; Marcus, Carole L.

2012-01-01

Study Objectives: Abnormal ventilatory drive may contribute to the pathophysiology of the childhood obstructive sleep apnea syndrome (OSAS). Concomitant with the obesity epidemic, more adolescents are developing OSAS. However, few studies have specifically evaluated the obese adolescent group. The authors hypothesized that obese adolescents with OSAS would have a blunted hypercapnic ventilatory response (HCVR) while awake and blunted ventilatory responses to carbon dioxide (CO2) during sleep compared with obese and lean adolescents without OSAS. Design: CVR was measured during wakefulness. During nonrapid eye movement (NREM) and rapid eye movement (REM) sleep, respiratory parameters and genioglossal electromyogram were measured during CO2 administration in comparison with room air in obese adolescents with OSAS, obese control study participants, and lean control study participants. Setting: Sleep laboratory. Participants: Twenty-eight obese patients with OSAS, 21 obese control study participants, and 37 lean control study participants. Results: The obese OSAS and obese control groups had a higher HCVR compared with the lean control group during wakefulness. During both sleep states, all 3 groups had a response to CO2; however, the obese OSAS group had lower percentage changes in minute ventilation, inspiratory flow, inspiratory time, and tidal volume compared with the 2 control groups. There were no significance differences in genioglossal activity between groups. Conclusions: HCVR during wakefulness is increased in obese adolescents. Obese adolescents with OSAS have blunted ventilatory responses to CO2 during sleep and do not have a compensatory prolongation of inspiratory time, despite having normal CO2 responsivity during wakefulness. Central drive may play a greater role than upper airway neuromotor tone in adapting to hypercapnia. Citation: Yuan H; Pinto SJ; Huang J; McDonough JM; Ward MB; Lee YN; Bradford RM; Gallagher PR; Shults J; Konstantinopoulou S; Samuel JM; Katz ES; Hua S; Tapia IE; Marcus CL. Ventilatory responses to hypercapnia during wakefulness and sleep in obese adolescents with and without obstructive sleep apnea syndrome. SLEEP 2012;35(9):1257–1267. PMID:22942504

Respiratory drives and exercise in menstrual cycles of athletic and nonathletic women.

PubMed

Schoene, R B; Robertson, H T; Pierson, D J; Peterson, A P

1981-06-01

To investigate the influence of the midluteal and midfollicular phases of the menstrual cycle on exercise performance and ventilatory drives, we studied six outstanding female athletes, six controls with normal menstrual cycles, and six outstanding athletes who were amenorrheic. In all menstruating subjects resting minute ventilation (Ve) and mouth occlusion pressures (P0.1) were higher in the luteal phase (p less than k0.0001 and p less than 0.02, respectively),. Hypoxic (expressed as the hyperbolic shape parameter A) and hypercapnic (expressed as S, deltaVE/delta PAco2) ventilatory responses were increase in the luteal phase (p less than 0.01). The athletes had lower A values during the luteal phase than the nonathletes (p less than 0.001). Maximal exercise response, expressed either as total exercise time or maximum O2 consumption or CO2 production (VO2 max or Vco2 max) was decreased during the luteal phase but was significantly different at a p less than 0.05 level only among the nonathletes. Ventilatory equivalent (VE/VO2) during progressive exercise on a bicycle ergometer was significantly increased during the luteal phase. The amenorrheic athletes showed no changes between the two test periods. The luteal phase of the menstrual cycle induced increases in ventilatory drives and exercise ventilation in both athletes and controls, but the athletes, in contrast to controls, demonstrated no significant decrease in exercise performance in the luteal phase.

Cerebral Blood Flow Response to Hypercapnia in Children with Obstructive Sleep Apnea Syndrome.

PubMed

Busch, David R; Lynch, Jennifer M; Winters, Madeline E; McCarthy, Ann L; Newland, John J; Ko, Tiffany; Cornaglia, Mary Anne; Radcliffe, Jerilynn; McDonough, Joseph M; Samuel, John; Matthews, Edward; Xiao, Rui; Yodh, Arjun G; Marcus, Carole L; Licht, Daniel J; Tapia, Ignacio E

2016-01-01

Children with obstructive sleep apnea syndrome (OSAS) often experience periods of hypercapnia during sleep, a potent stimulator of cerebral blood flow (CBF). Considering this hypercapnia exposure during sleep, it is possible that children with OSAS have abnormal CBF responses to hypercapnia even during wakefulness. Therefore, we hypothesized that children with OSAS have blunted CBF response to hypercapnia during wakefulness, compared to snorers and controls. CBF changes during hypercapnic ventilatory response (HCVR) were tested in children with OSAS, snorers, and healthy controls using diffuse correlation spectroscopy (DCS). Peak CBF changes with respect to pre-hypercapnic baseline were measured for each group. The study was conducted at an academic pediatric sleep center. Twelve children with OSAS (aged 10.1 ± 2.5 [mean ± standard deviation] y, obstructive apnea hypopnea index [AHI] = 9.4 [5.1-15.4] [median, interquartile range] events/hour), eight snorers (11 ± 3 y, 0.5 [0-1.3] events/hour), and 10 controls (11.4 ± 2.6 y, 0.3 [0.2-0.4] events/hour) were studied. The fractional CBF change during hypercapnia, normalized to the change in end-tidal carbon dioxide, was significantly higher in controls (9 ± 1.8 %/mmHg) compared to OSAS (7.1 ± 1.5, P = 0.023) and snorers (6.7 ± 1.9, P = 0.025). Children with OSAS and snorers have blunted CBF response to hypercapnia during wakefulness compared to controls. Noninvasive DCS blood flow measurements of hypercapnic reactivity offer insights into physiopathology of OSAS in children, which could lead to further understanding about the central nervous system complications of OSAS. © 2016 Associated Professional Sleep Societies, LLC.

Ionotropic but not metabotropic glutamatergic receptors in the locus coeruleus modulate the hypercapnic ventilatory response in unanaesthetized rats.

PubMed

Taxini, C L; Puga, C C I; Dias, M B; Bícego, K C; Gargaglioni, L H

2013-05-01

Central chemoreceptors are important to detect changes of CO2/H(+), and the Locus coeruleus (LC) is one of the many putative central chemoreceptor sites. Here, we studied the contribution of LC glutamatergic receptors on ventilatory, cardiovascular and thermal responses to hypercapnia. To this end, we determined pulmonary ventilation (V(E)), body temperatures (T(b)), mean arterial pressure (MAP) and heart rate (HR) of male Wistar rats before and after unilateral microinjection of kynurenic acid (KY, an ionotropic glutamate receptor antagonist, 10 nmol/0.1 μL) or α-methyl-4-carboxyphenylglycine (MCPG, a metabotropic glutamate receptor antagonist, 10 nmol/0.1 μL) into the LC, followed by 60 min of air breathing or hypercapnia exposure (7% CO2). Ventilatory response to hypercapnia was higher in animals treated with KY intra-LC (1918.7 ± 275.4) compared with the control group (1057.8 ± 213.9, P < 0.01). However, the MCPG treatment within the LC had no effect on the hypercapnia-induced hyperpnea. The cardiovascular and thermal controls were not affected by hypercapnia or by the injection of KY and MCPG in the LC. These data suggest that glutamate acting on ionotropic, but not metabotropic, receptors in the LC exerts an inhibitory modulation of hypercapnia-induced hyperpnea. Acta Physiologica © 2013 Scandinavian Physiological Society.

Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties

PubMed Central

Gonzalez-Obeso, Elvira; Docio, Inmaculada; Olea, Elena; Cogolludo, Angel; Obeso, Ana; Rocher, Asuncion; Gomez-Niño, Angela

2017-01-01

Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K+ currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied. PMID:28533756

Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties.

PubMed

Gonzalez-Obeso, Elvira; Docio, Inmaculada; Olea, Elena; Cogolludo, Angel; Obeso, Ana; Rocher, Asuncion; Gomez-Niño, Angela

2017-01-01

Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO 2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K + currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca 2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied.

Ventilatory, metabolic, and thermal responses to hypercapnia in female rats: effects of estrous cycle, ovariectomy, and hormonal replacement.

PubMed

Marques, Danuzia A; de Carvalho, Débora; da Silva, Glauber S F; Szawka, Raphael E; Anselmo-Franci, Janete A; Bícego, Kênia C; Gargaglioni, Luciane H

2015-07-01

The aim of this study was to examine how estrous cycle, ovariectomy, and hormonal replacement affect the respiratory [ventilation (V̇e), tidal volume, and respiratory frequency], metabolic (V̇o2), and thermoregulatory (body temperature) responses to hypercapnia (7% CO2) in female Wistar rats. The parameters were measured in rats during different phases of the estrous cycle, and also in ovariectomized (OVX) rats supplemented with 17β-estradiol (OVX+E2), with a combination of E2 and progesterone (OVX+E2P), or with corn oil (OVX+O, vehicle). All experiments were conducted on day 8 after ovariectomy. The intact animals did not present alterations during normocapnia or under hypercapnia in V̇e, tidal volume, respiratory frequency, V̇o2, and V̇e/V̇o2 in the different phases of the estrous cycle. However, body temperature was higher in female rats on estrus. Hormonal replacement did not change the ventilatory, thermoregulatory, or metabolic parameters during hypercapnia, compared with the OVX animals. Nevertheless, OVX+E2, OVX+E2P, and OVX+O presented lower hypercapnic ventilatory responses compared with intact females on the day of estrus. Also, rats in estrus showed higher V̇e and V̇e/V̇o2 during hypercapnia than OVX animals. The data suggest that other gonadal factors, besides E2 and P, are possibly involved in these responses. Copyright © 2015 the American Physiological Society.

Classic conditioning of the ventilatory responses in rats.

PubMed

Nsegbe, E; Vardon, G; Perruchet, P; Gallego, J

1997-10-01

Recent authors have stressed the role of conditioning in the control of breathing, but experimental evidence of this role is still sparse and contradictory. To establish that classic conditioning of the ventilatory responses can occur in rats, we performed a controlled experiment in which a 1-min tone [conditioned stimulus (CS)] was paired with a hypercapnic stimulus [8.5% CO2, unconditioned stimulus (US)]. The experimental group (n = 9) received five paired CS-US presentations, followed by one CS alone to test conditioning. This sequence was repeated six times. The control group (n = 7) received the same number of CS and US, but each US was delivered 3 min after the CS. We observed that after the CS alone, breath duration was significantly longer in the experimental than in the control group and mean ventilation was significantly lower, thus showing inhibitory conditioning. This conditioning may have resulted from the association between the CS and the inhibitory and aversive effects of CO2. The present results confirmed the high sensitivity of the respiratory controller to conditioning processes.

Endoscopic lung volume reduction coil treatment in patients with chronic hypercapnic respiratory failure: an observational study.

PubMed

Simon, Marcel; Harbaum, Lars; Oqueka, Tim; Kluge, Stefan; Klose, Hans

2017-01-01

Endoscopic lung volume reduction coil (LVRC) treatment is an option for selected patients with severe emphysema. In the advanced stages, emphysema leads to respiratory failure: hypoxemia and eventually chronic hypercapnic respiratory failure. It can be hypothesized that LVRC treatment, a procedure targeting hyperinflation and thereby reducing ventilatory workload, may be especially beneficial in patients with chronic hypercapnic respiratory failure. This study was conducted to gain first insights into the effects and the safety of LVRC treatment in patients with emphysema and chronic hypercapnic respiratory failure. A retrospective observational study conducted in the Department of Respiratory Medicine at the University Medical Center Hamburg-Eppendorf, Germany on all patients with chronic hypercapnic respiratory failure in whom bilateral LVRC treatment was performed between 1 April 2012 and 30 September 2015. During the study period, bilateral LVRC treatment was performed in 10 patients with chronic hypercapnic respiratory failure. Compared with baseline, bilateral LVRC treatment led to a significant increase in mean forced expiratory volume in one second (FEV 1 ) from 0.5 ± 0.1 l to 0.6 ± 0.2 l ( p = 0.004), a decrease in residual volume (RV) from 6.1 ± 0.9 l to 5.6 ± 1.1 l ( p = 0.02) and a reduction in partial pressure of carbon dioxide in arterial blood (PaCO 2 ) from 53 ± 5 mmHg to 48 ± 4 mmHg ( p = 0.03). One case of hemoptysis requiring readmission to hospital was the only severe adverse event. LVRC treatment was safe and effective in patients with nonsevere chronic hypercapnic respiratory failure. It led not only to an improvement in lung function but also to a significant decrease in PaCO 2 .

The c-FOS Protein Immunohistological Detection: A Useful Tool As a Marker of Central Pathways Involved in Specific Physiological Responses In Vivo and Ex Vivo

PubMed Central

Perrin-Terrin, Anne-Sophie; Jeton, Florine; Pichon, Aurelien; Frugière, Alain; Richalet, Jean-Paul; Bodineau, Laurence; Voituron, Nicolas

2016-01-01

Many studies seek to identify and map the brain regions involved in specific physiological regulations. The proto-oncogene c-fos, an immediate early gene, is expressed in neurons in response to various stimuli. The protein product can be readily detected with immunohistochemical techniques leading to the use of c-FOS detection to map groups of neurons that display changes in their activity. In this article, we focused on the identification of brainstem neuronal populations involved in the ventilatory adaptation to hypoxia or hypercapnia. Two approaches were described to identify involved neuronal populations in vivo in animals and ex vivo in deafferented brainstem preparations. In vivo, animals were exposed to hypercapnic or hypoxic gas mixtures. Ex vivo, deafferented preparations were superfused with hypoxic or hypercapnic artificial cerebrospinal fluid. In both cases, either control in vivo animals or ex vivo preparations were maintained under normoxic and normocapnic conditions. The comparison of these two approaches allows the determination of the origin of the neuronal activation i.e., peripheral and/or central. In vivo and ex vivo, brainstems were collected, fixed, and sliced into sections. Once sections were prepared, immunohistochemical detection of the c-FOS protein was made in order to identify the brainstem groups of cells activated by hypoxic or hypercapnic stimulations. Labeled cells were counted in brainstem respiratory structures. In comparison to the control condition, hypoxia or hypercapnia increased the number of c-FOS labeled cells in several specific brainstem sites that are thus constitutive of the neuronal pathways involved in the adaptation of the central respiratory drive. PMID:27167092

Minocycline blocks glial cell activation and ventilatory acclimatization to hypoxia.

PubMed

Stokes, Jennifer A; Arbogast, Tara E; Moya, Esteban A; Fu, Zhenxing; Powell, Frank L

2017-04-01

Ventilatory acclimatization to hypoxia (VAH) is the time-dependent increase in ventilation, which persists upon return to normoxia and involves plasticity in both central nervous system respiratory centers and peripheral chemoreceptors. We investigated the role of glial cells in VAH in male Sprague-Dawley rats using minocycline, an antibiotic that inhibits microglia activation and has anti-inflammatory properties, and barometric pressure plethysmography to measure ventilation. Rats received either minocycline (45mg/kg ip daily) or saline beginning 1 day before and during 7 days of chronic hypoxia (CH, Pi O 2  = 70 Torr). Minocycline had no effect on normoxic control rats or the hypercapnic ventilatory response in CH rats, but minocycline significantly ( P < 0.001) decreased ventilation during acute hypoxia in CH rats. However, minocycline administration during only the last 3 days of CH did not reverse VAH. Microglia and astrocyte activation in the nucleus tractus solitarius was quantified from 30 min to 7 days of CH. Microglia showed an active morphology (shorter and fewer branches) after 1 h of hypoxia and returned to the control state (longer filaments and extensive branching) after 4 h of CH. Astrocytes increased glial fibrillary acidic protein antibody immunofluorescent intensity, indicating activation, at both 4 and 24 h of CH. Minocycline had no effect on glia in normoxia but significantly decreased microglia activation at 1 h of CH and astrocyte activation at 24 h of CH. These results support a role for glial cells, providing an early signal for the induction but not maintenance of neural plasticity underlying ventilatory acclimatization to hypoxia. NEW & NOTEWORTHY The signals for neural plasticity in medullary respiratory centers underlying ventilatory acclimatization to chronic hypoxia are unknown. We show that chronic hypoxia activates microglia and subsequently astrocytes. Minocycline, an antibiotic that blocks microglial activation and has anti-inflammatory properties, also blocks astrocyte activation in respiratory centers during chronic hypoxia and ventilatory acclimatization. However, minocycline cannot reverse ventilatory acclimatization after it is established. Hence, glial cells may provide signals that initiate but do not sustain ventilatory acclimatization. Copyright © 2017 the American Physiological Society.

Minocycline blocks glial cell activation and ventilatory acclimatization to hypoxia

PubMed Central

Arbogast, Tara E.; Moya, Esteban A.; Fu, Zhenxing; Powell, Frank L.

2017-01-01

Ventilatory acclimatization to hypoxia (VAH) is the time-dependent increase in ventilation, which persists upon return to normoxia and involves plasticity in both central nervous system respiratory centers and peripheral chemoreceptors. We investigated the role of glial cells in VAH in male Sprague-Dawley rats using minocycline, an antibiotic that inhibits microglia activation and has anti-inflammatory properties, and barometric pressure plethysmography to measure ventilation. Rats received either minocycline (45mg/kg ip daily) or saline beginning 1 day before and during 7 days of chronic hypoxia (CH, PiO2 = 70 Torr). Minocycline had no effect on normoxic control rats or the hypercapnic ventilatory response in CH rats, but minocycline significantly (P < 0.001) decreased ventilation during acute hypoxia in CH rats. However, minocycline administration during only the last 3 days of CH did not reverse VAH. Microglia and astrocyte activation in the nucleus tractus solitarius was quantified from 30 min to 7 days of CH. Microglia showed an active morphology (shorter and fewer branches) after 1 h of hypoxia and returned to the control state (longer filaments and extensive branching) after 4 h of CH. Astrocytes increased glial fibrillary acidic protein antibody immunofluorescent intensity, indicating activation, at both 4 and 24 h of CH. Minocycline had no effect on glia in normoxia but significantly decreased microglia activation at 1 h of CH and astrocyte activation at 24 h of CH. These results support a role for glial cells, providing an early signal for the induction but not maintenance of neural plasticity underlying ventilatory acclimatization to hypoxia. NEW & NOTEWORTHY The signals for neural plasticity in medullary respiratory centers underlying ventilatory acclimatization to chronic hypoxia are unknown. We show that chronic hypoxia activates microglia and subsequently astrocytes. Minocycline, an antibiotic that blocks microglial activation and has anti-inflammatory properties, also blocks astrocyte activation in respiratory centers during chronic hypoxia and ventilatory acclimatization. However, minocycline cannot reverse ventilatory acclimatization after it is established. Hence, glial cells may provide signals that initiate but do not sustain ventilatory acclimatization. PMID:28100653

Oxygen and carbon dioxide sensitivity of ventilation in amphibious crabs, Cardisoma guanhumi, breathing air and water.

PubMed

Gannon, Andrew T; Henry, Raymond P

2004-05-01

Amphibious crabs, Cardisoma guanhumi, were acclimated to breathing either air or water and exposed to altered levels of oxygen and/or carbon dioxide in the medium. Hypercapnia (22, 36 and 73 torr CO(2)) stimulated a significant hypercapnic ventilatory response (HCVR) in both groups of crabs, with a much greater effect on scaphognathite frequency (Deltaf(SC)=+700%) in air-breathing crabs than water-breathing crabs (Deltaf(SC)=+100%). In contrast, hyperoxia induced significant hypoventilation in both sets of crabs. However, simultaneous hyperoxia and hypercapnia triggered a greater than 10-fold increase in f(SC) in air-breathing crabs but no change in water-breathing crabs. For water-breathing crabs hypoxia simultaneous with hypercapnia triggered the same response as hypoxia alone-bradycardia (-50%), and a significant increase in f(SC) at moderate exposures but not at the more extreme levels. The response of air-breathing crabs to hypoxia concurrent with hypercapnia was proportionally closer to the response to hypercapnia alone than to hypoxia. Thus, C. guanhumi were more sensitive to ambient CO(2) than O(2) when breathing air, characteristic of fully terrestrial species, and more sensitive to ambient O(2) when breathing water, characteristic of fully aquatic species. C. guanhumi possesses both an O(2)- and a CO(2)-based ventilatory drive whether breathing air or water, but the relative importance switches when the respiratory medium is altered.

In hamsters the D1 receptor antagonist SCH23390 depresses ventilation during hypoxia.

PubMed

Schlenker, Evelyn H

2008-01-02

During exposure of animals to hypoxia, brain and blood dopamine levels increase stimulating dopaminergic receptors which influence the integrated ventilatory response to low oxygen. The purpose of the present study is to test the hypothesis that in conscious hamsters, systemic antagonism of D(1) receptors would depress their breathing in air and in response to hypoxic and hypercapnic challenges. Nine male hamsters were treated with saline or 0.25 mg/kg SCH-23390 (SCH), a D(1) receptor antagonist that crosses the blood-brain barrier. Ventilation was determined using the barometric method, and oxygen consumption and CO(2) production were evaluated utilizing the flow-through method. During exposure to air, SCH decreased frequency of breathing. During exposure to hypoxia (10% oxygen in nitrogen), relative to saline, SCH-treated hamsters decreased minute ventilation by decreasing tidal volume and oxygen consumption but not CO(2) production. During exposure to hypercapnia (5% CO(2) in 95% O(2)), frequency of breathing was decreased with SCH, but there was no significant effect on minute ventilation. Relative to saline treatment body temperature was lower in SCH-treated hamsters by 0.6 degrees C. These results demonstrate that in hamsters D(1) receptors can modulate control of ventilation in air and during hypoxia and hypercapnic exposures. Whether D(1) receptors located centrally or on carotid bodies modulate these effects is not clear from this study.

Optical imaging of the ventral medullary surface of developing kittens during ventilatory challenges.

PubMed

Gozal, D; Dong, X W; Rector, D M; Harper, R K; Harper, R M

1996-01-01

We used large-array optical recording procedures to examine maturation of regional neural activity within the ventral medullary surface (VMS) of anaesthetized kittens during graded hypercapnic and hypoxic challenges. The VMS was exposed through a ventral surgical approach in 10, 20, 30, and 45-day-old kittens and in adult cats under sodium pentobarbital anaesthesia. Arterial pressure, costal diaphragmatic EMG, and ECG were continuously monitored. A coherent image conduit with 12 mu fibre resolution was attached to a charge-coupled-device camera and positioned over the VMS. Reflected 660 nm light was digitized continuously at 2-s intervals during a baseline period, hyperoxic hypercapnia, (3, 5, and 10% CO2 in O2), and poikylocapnic hypoxia (6%, 9%, and 12% O2 in N2), and recovery. Sixty to seventy-five images within each epoch were averaged, and subtracted from baseline. Regional differences within the image were determined by ANOVA procedures (alpha = 0.05). During hypercapnia, an overall decrease in neural activity (increase in scattered light) occurred, which was marginally age-dependent. By 30 days, regional bidirectional reflectance changes in response to CO2 emerged in a small proportion of animals, and were similar to adult responses. Hypoxia induced a dose- and age-dependent decrease in overall scattered light. Transient "on" and "off" responses were common under both ventilatory stimuli. In 20-30-day kittens, marked rebound responses in reflectance accompanied cessation of hypoxic stimuli; such patterns were absent at other ages. At 30 days, a caudal-rostral bidirectionality in response to mild hypoxia (12% O2) began to emerge in a subset of animals. We conclude that dose-dependent response to ventilatory stimuli occur in the VMS at all post-natal ages of the kitten; however, in hypoxia, the magnitude of the overall reflectance changes is diminished relative to adult patterns. Rebound responses to hypoxia are present at particular ages, and older kittens begin to show a topographical organization of neural activation.

Effects of a Single Bout of Interval Hypoxia on Cardiorespiratory Control in Patients With Type 1 Diabetes

PubMed Central

Duennwald, Tobias; Bernardi, Luciano; Gordin, Daniel; Sandelin, Anna; Syreeni, Anna; Fogarty, Christopher; Kytö, Janne P.; Gatterer, Hannes; Lehto, Markku; Hörkkö, Sohvi; Forsblom, Carol; Burtscher, Martin; Groop, Per-Henrik

2013-01-01

Hypoxemia is common in diabetes, and reflex responses to hypoxia are blunted. These abnormalities could lead to cardiovascular/renal complications. Interval hypoxia (IH) (5–6 short periods of hypoxia each day over 1–3 weeks) was successfully used to improve the adaptation to hypoxia in patients with chronic obstructive pulmonary disease. We tested whether IH over 1 day could initiate a long-lasting response potentially leading to better adaptation to hypoxia. In 15 patients with type 1 diabetes, we measured hypoxic and hypercapnic ventilatory responses (HCVRs), ventilatory recruitment threshold (VRT-CO2), baroreflex sensitivity (BRS), blood pressure, and blood lactate before and after 0, 3, and 6 h of a 1-h single bout of IH. All measurements were repeated on a placebo day (single-blind protocol, randomized sequence). After IH (immediately and after 3 h), hypoxic and HCVR increased, whereas the VRT-CO2 dropped. No such changes were observed on the placebo day. Systolic and diastolic blood pressure increased, whereas blood lactate decreased after IH. Despite exposure to hypoxia, BRS remained unchanged. Repeated exposures to hypoxia over 1 day induced an initial adaptation to hypoxia, with improvement in respiratory reflexes. Prolonging the exposure to IH (>2 weeks) in type 1 diabetic patients will be a matter for further studies. PMID:23733200

Respiratory CO2 response depends on plasma bicarbonate concentration in mechanically ventilated patients.

PubMed

Rialp, G; Raurich, J M; Llompart-Pou, J A; Ayestarán, I; Ibáñez, J

2014-05-01

There is controversy about the effects of high plasma bicarbonate concentration ([HCO3(-)]) and the CO2 response test. We analyzed the relationship between [HCO3(-)] and the variation in hydrogen ion concentration (pH) for a given change in PaCO2, and its effects upon CO2 response. A retrospective study was carried out. Two intensive care units. Subjects with and without chronic obstructive pulmonary disease (COPD), at the beginning of weaning from mechanical ventilation. The CO2 response was evaluated by the re-inhalation of expired air method, measuring the hypercapnic ventilatory response (ΔVE/ΔPaCO2) and hypercapnic drive response (ΔP01/ΔPaCO2), where VE is minute volume and P0.1 is airway occlusion pressure 0.1s after the initiation of inspiration. [HCO3(-)] and CO2 response. A total of 120 patients in the non-COPD group and 48 in the COPD group were studied. COPD patients had higher mean [HCO3(-)] than non-COPD patients (33.2 ± 5.4 vs. 25.7 ± 3.7 mmol/l, p<0.001). In both non-COPD and COPD patients we observed a significant inverse linear relationship between [HCO3(-)] and pH change per mmHg of PaCO2 (p<0.001), ΔVE/ΔPaCO2 (p<0.001) and ΔP0.1/ΔPaCO2 (p<0.001). There is an inverse linear relationship between [HCO3(-)] and the variation of pH for a given change in PaCO2 and the CO2 response. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Hypothyroidism Attenuates SCH 23390-mediated Depression of Breathing and Decreases D1 Receptor Expression in Carotid Bodies, PVN and Striatum of Hamsters

PubMed Central

Schlenker, Evelyn H.; Schultz, Harold D.

2011-01-01

Hypothyroidism can lead to depressed breathing. We determined if propylthiouracil (PTU)–induced hypothyroidism in hamsters (HH) altered dopamine D1 receptor expression, D1 receptor-modulated ventilation, and ventilatory chemoreflex activation by hypoxia or hypercapnia. Hypothyroidism was induced by administering 0.04% PTU in drinking water for three months. Ventilation was evaluated following saline or 0.25 mg/kg SCH 23390, a D1 receptor antagonist, while awake hamsters breathed normoxic (21% O2 in N2), hypoxic (10% O2 in N2) and hypercapnic (5% CO2 in O2) air. Relative to euthyroid hamsters (EH), HH exhibited decreased D1 receptor protein levels in carotid bodies, striatum, and hypothalamic paraventricular nucleus, but not in the nucleus tractus solitarius. Relative to EH, HH exhibited lower ventilation during exposure to normoxia, hypoxia, or hypercapnia, but comparable ventilatory responsiveness to chemoreflex activation. SCH 23390 decreased ventilation of EH hamsters exposed to normoxia, hypoxia, and hypercapnia. In HH SCH 23390 increased ventilation during baseline normoxia and did not affect ventilation during exposure to hypoxia and hypercapnia, resulting in reduced ventilatory responsivess to chemoreflex activation by hypoxia and hypercapnia. Furthermore, in HH D1 receptor protein levels are decreased in several brain regions and within the carotid bodies. Moreover, D1 receptor-modulation of breathing at rest and during gas exposures were depressed in EH but not HH. PMID:21669406

Respiratory mechanics and ventilatory control in overlap syndrome and obesity hypoventilation

PubMed Central

2013-01-01

The overlap syndrome of obstructive sleep apnoea (OSA) and chronic obstructive pulmonary disease (COPD), in addition to obesity hypoventilation syndrome, represents growing health concerns, owing to the worldwide COPD and obesity epidemics and related co-morbidities. These disorders constitute the end points of a spectrum with distinct yet interrelated mechanisms that lead to a considerable health burden. The coexistence OSA and COPD seems to occur by chance, but the combination can contribute to worsened symptoms and oxygen desaturation at night, leading to disrupted sleep architecture and decreased sleep quality. Alveolar hypoventilation, ventilation-perfusion mismatch and intermittent hypercapnic events resulting from apneas and hypopneas contribute to the final clinical picture, which is quite different from the “usual” COPD. Obesity hypoventilation has emerged as a relatively common cause of chronic hypercapnic respiratory failure. Its pathophysiology results from complex interactions, among which are respiratory mechanics, ventilatory control, sleep-disordered breathing and neurohormonal disturbances, such as leptin resistance, each of which contributes to varying degrees in individual patients to the development of obesity hypoventilation. This respiratory embarrassment takes place when compensatory mechanisms like increased drive cannot be maintained or become overwhelmed. Although a unifying concept for the pathogenesis of both disorders is lacking, it seems that these patients are in a vicious cycle. This review outlines the major pathophysiological mechanisms believed to contribute to the development of these specific clinical entities. Knowledge of shared mechanisms in the overlap syndrome and obesity hypoventilation may help to identify these patients and guide therapy. PMID:24256627

Effects of Five Nights under Normobaric Hypoxia on Sleep Quality.

PubMed

Hoshikawa, Masako; Uchida, Sunao; Osawa, Takuya; Eguchi, Kazumi; Arimitsu, Takuma; Suzuki, Yasuhiro; Kawahara, Takashi

2015-07-01

The purpose of this study was to evaluate the effects of five nights' sleep under normobaric hypoxia on ventilatory acclimatization and sleep quality. Seven men initially slept for six nights under normoxia and then for five nights under normobaric hypoxia equivalent to a 2000-m altitude. Nocturnal polysomnograms (PSGs), arterial blood oxygen saturation (SpO2), and respiratory events were recorded on the first and fifth nights under both conditions. The hypoxic ventilatory response (HVR), hypercapnic ventilatory response (HCVR), and resting end-tidal CO2 (resting PETCO2) were measured three times during the experimental period. The duration of slow-wave sleep (SWS: stage N3) and the whole-night delta (1-3 Hz) power of nonrapid eye movement (NREM) sleep EEG decreased on the first night under hypoxia. This hypoxia-induced sleep quality deterioration on the first night was accompanied by a lower mean and minimum SpO2, a longer time spent with SpO2 below 90% (<90% SpO2 time), and more episodes of respiratory disturbance. On the fifth night, the SWS duration and whole-night delta power did not differ between the conditions. Although the mean SpO2 under hypoxia was still lower than under normoxia, the minimum SpO2 increased, and the <90% SpO2 time and number of episodes of respiratory disturbance decreased during the five nights under hypoxia. The HVR increased and resting PETCO2 decreased after five nights under hypoxia. The results suggest that five nights under hypoxia improves the sleep quality. This may be derived from improvements of respiratory disturbances, the minimum SpO2, and <90% SpO2 time.

The rostral medulla of bullfrog tadpoles contains critical lung rhythmogenic and chemosensitive regions across metamorphosis.

PubMed

Reed, Mitchell D; Iceman, Kimberly E; Harris, Michael B; Taylor, Barbara E

2018-06-08

The development of amphibian breathing provides insight into vertebrate respiratory control mechanisms. Neural oscillators in the rostral and caudal medulla drive ventilation in amphibians, and previous reports describe ventilatory oscillators and CO 2 sensitive regions arise during different stages of amphibian metamorphosis. However, inconsistent findings have been enigmatic, and make comparisons to potential mammalian counterparts challenging. In the current study we assessed amphibian central CO 2 responsiveness and respiratory rhythm generation during two different developmental stages. Whole-nerve recordings of respiratory burst activity in cranial and spinal nerves were made from intact or transected brainstems isolated from tadpoles during early or late stages of metamorphosis. Brainstems were transected at the level of the trigeminal nerve, removing rostral structures including the nucleus isthmi, midbrain, and locus coeruleus, or transected at the level of the glossopharyngeal nerve, removing the putative buccal oscillator and caudal medulla. Removal of caudal structures stimulated the frequency of lung ventilatory bursts and revealed a hypercapnic response in normally unresponsive preparations derived from early stage tadpoles. In preparations derived from late stage tadpoles, removal of rostral or caudal structures reduced lung burst frequency, while CO 2 responsiveness was retained. Our results illustrate that structures within the rostral medulla are capable of sensing CO 2 throughout metamorphic development. Similarly, the region controlling lung ventilation appears to be contained in the rostral medulla throughout metamorphosis. This work offers insight into the consistency of rhythmic respiratory and chemosensitive capacities during metamorphosis. Copyright © 2018. Published by Elsevier Inc.

Intermittent hypercapnia induces long-lasting ventilatory plasticity to enhance CO2 responsiveness to overcome dysfunction

NASA Astrophysics Data System (ADS)

Mosher, Bryan Patrick

The ability of the brain to detect (central CO2 chemosensitivity) and respond to (central CO2 chemoresponsiveness) changes in tissue CO2/pH, is a homeostatic process essential for mammalian life. Dysfunction of the serotonin (5-HT) mechanisms compromises ventilatory CO 2 chemosensitivity/responsiveness and may enhance vulnerability to pathologies such as the Sudden Infant Death Syndrome (SIDS). The laboratory of Dr. Michael Harris has shown medullary raphe contributions to central chemosensitivity involving both 5-HT- and gamma-aminobutyric acid (GABA)-mediated mechanisms. I tested the hypothesis that postnatal exposure to mild intermittent hypercapnia (IHc) induces respiratory plasticity, due in part to strengthening of bicuculline- and saclofen-sensitive mechanisms (GABAA and GABAB receptor antagonists respectively). Rats were exposed to IHc-pretreatment (8 cycles of 5 % CO2) for 5 days beginning at postnatal day 12 (P12). I subsequently assessed CO2 responsiveness using an in situ perfused brainstem preparation. Hypercapnic responses were determined with and without pharmacological manipulation. In addition, IHc-pretreatment effectiveness was tested for its ability to overcome dysfunction in the CO2 responsiveness induced by a dietary tryptophan restriction. This dysfunctional CO2 responsiveness has been suggested to arise from a chronic, partial 5-HT reduction imparted by the dietary restriction. Results show IHc-pretreatment induced plasticity sufficient for CO2 responsiveness despite removal of otherwise critical ketanserin-sensitive mechanisms. CO2 responsiveness following IHc-pretreatment was absent if ketanserin was combined with bicuculline and saclofen, indicating that the plasticity was dependent upon bicuculline- and saclofen-sensitive mechanisms. IHc--induced plasticity was also capable of overcoming the ventilatory defects associated with maternal dietary restriction. Duration of IHc-induced plasticity was also investigated and found to last far into life (up to P65). Furthermore, I performed experiments to investigate if IHc-induced plasticity was more robust at a specific developmental period. No such critical period was identified as IHc-pretreatment induced robust respiratory plasticity when administered at all developmental periods tested (P12-16, P21-25 and P36-0). I propose that IHc-induced plasticity may be able to reduce the severity of reflex dysfunctions underlying pathologies such as SIDS.

Postural control and ventilatory drive during voluntary hyperventilation and carbon dioxide rebreathing.

PubMed

David, Pascal; Laval, David; Terrien, Jérémy; Petitjean, Michel

2012-01-01

The present study sought to establish links between hyperventilation and postural stability. Eight university students were asked to stand upright under two hyperventilation conditions applied randomly: (1) a metabolic hyperventilation induced by 5 min of hypercapnic-hyperoxic rebreathing (CO(2)-R); and, (2) a voluntary hyperventilation (VH) of 3 min imposed by a metronome set at 25 cycles per min. Recordings were obtained with eyes open, with the subjects standing on a force plate over 20-s periods. Ventilatory response, displacements in the centre of pressure in both the frontal and sagittal planes and fluctuations in the three planes of the ground reaction force were monitored in the time and frequency domains. Postural changes related to respiratory variations were quantified by coherence analysis. Myoelectric activities of the calf muscles were recorded using surface electromyography. Force plate measurements revealed a reduction in postural stability during both CO(2)-R and VH conditions, mainly in the sagittal plane. Coherence analysis provided evidence of a ventilatory origin in the vertical ground reaction force fluctuations during VH. Electromyographic analyses showed different leg muscles strategies, assuming the existence of links between the control of respiration and the control of posture. Our results suggest that the greater disturbing effects caused by voluntary hyperventilation on body balance are more compensated when respiration is under automatic control. These findings may have implications for understanding the organisation of postural and respiratory activities and suggest that stability of the body may be compromised in situations in which respiratory demand increases and requires voluntary control.

Systemic blockade of nicotinic and purinergic receptors inhibits ventilation and increases apnoea frequency in newborn rats.

PubMed

Niane, Lalah M; Joseph, Vincent; Bairam, Aida

2012-08-01

We hypothesized that the combined blockade of peripheral cholinergic and purinergic receptors alters the baseline breathing pattern and respiratory responses to carotid body stimuli (hypoxia, hyperoxia and hypercapnia). Rat pups at 4 (P4) and 12 days of postnatal age (P12) received an intraperitoneal injection of either saline vehicle or hexamethonium + suramin (Hex, 1 mg kg(-1), nicotinic receptor antagonist; Sur, 40 mg kg(-1), P2X receptor antagonist; both of which act mainly on peripheral receptors). Compared with the control animals (saline-injected rats), the Hex + Sur-treated rats demonstrated the following features: (1) decreased baseline ventilation and increased frequency of apnoea and breath-by-breath irregularities, with a larger effect in the P4 than in the P12 rats; (2) a decreased peak minute ventilation and respiratory frequency response to hypoxia (fractional inspired oxygen 12%), with a greater effect in the P12 than in the P4 rats; (3) an attenuated decline of the respiratory frequency during hyperoxia (fractional inspired oxygen 50%) to a similar magnitude in rats of both ages; and (4) a decreased hypercapnic ventilatory response (fractional inspired carbon dioxide 5%) to a similar magnitude in rats of both ages. We conclude that the cholinergic nicotinic and purinergic P2X receptors are essential to maintain an adequate baseline pattern in normoxia. They also contribute, albeit not exclusively, to the hypoxic ventilatory response, with an age-specific effect, most probably linked to the cholinergic component, which might partly underlie the postnatal maturation of peripheral chemoreceptors.

Regulation of breathing and body temperature of a burrowing rodent during hypoxic-hypercapnia.

PubMed

Barros, Renata C H; Abe, Augusto S; Cárnio, Evelin C; Branco, Luiz G S

2004-05-01

Burrowing mammals usually have low respiratory sensitivity to hypoxia and hypercapnia. However, the interaction between ventilation (V), metabolism and body temperature (Tb) during hypoxic-hypercapnia has never been addressed. We tested the hypothesis that Clyomys bishopi, a burrowing rodent of the Brazilian cerrado, shows a small ventilatory response to hypoxic-hypercapnia, accompanied by a marked drop in Tb and metabolism. V, Tb and O(2) consumption (V?O(2)) of C. bishopi were measured during exposure to air, hypoxia (10% and 7% O(2)), hypercapnia (3% and 5% CO(2)) and hypoxic-hypercapnia (10% O(2)+ 3% CO(2)). Hypoxia of 7% but not 10%, caused a significant increase in V, and a significant drop in Tb. Both hypoxic levels decreased V?O(2) and 7% O(2) significantly increased V/V?O(2). Hypercapnia of 5%, but not 3%, elicited a significant increase in V, although no significant change in Tb, V?O(2) or V/V?O(2) was detected. A combination of 10% O(2) and 3% CO(2) had minor effects on V and Tb, while V?O(2) decreased and V/V?O(2) tended to increase. We conclude that C. bishopi has a low sensitivity not only to hypoxia and hypercapnia, but also to hypoxic-hypercapnia, manifested by a biphasic ventilatory response, a drop in metabolism and a tendency to increase V/V?O(2). The effect of hypoxic-hypercapnia was the summation of the hypoxia and hypercapnia effects, with respiratory responses tending to have hypercapnic patterns while metabolic responses, hypoxic patterns.

What Can We Apply to Manage Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Respiratory Failure?

PubMed

Kim, Deog Kyeom; Lee, Jungsil; Park, Ju Hee; Yoo, Kwang Ha

2018-04-01

Acute exacerbation(s) of chronic obstructive pulmonary disease (AECOPD) tend to be critical and debilitating events leading to poorer outcomes in relation to chronic obstructive pulmonary disease (COPD) treatment modalities, and contribute to a higher and earlier mortality rate in COPD patients. Besides pro-active preventative measures intended to obviate acquisition of AECOPD, early recovery from severe AECOPD is an important issue in determining the long-term prognosis of patients diagnosed with COPD. Updated GOLD guidelines and recently published American Thoracic Society/European Respiratory Society clinical recommendations emphasize the importance of use of pharmacologic treatment including bronchodilators, systemic steroids and/or antibiotics. As a non-pharmacologic strategy to combat the effects of AECOPD, noninvasive ventilation (NIV) is recommended as the treatment of choice as this therapy is thought to be most effective in reducing intubation risk in patients diagnosed with AECOPD with acute respiratory failure. Recently, a few adjunctive modalities, including NIV with helmet and helium-oxygen mixture, have been tried in cases of AECOPD with respiratory failure. As yet, insufficient documentation exists to permit recommendation of this therapy without qualification. Although there are too few findings, as yet, to allow for regular andr routine application of those modalities in AECOPD, there is anecdotal evidence to indicate both mechanical and physiological benefits connected with this therapy. High-flow nasal cannula oxygen therapy is another supportive strategy which serves to improve the symptoms of hypoxic respiratory failure. The therapy also produced improvement in ventilatory variables, and it may be successfully applied in cases of hypercapnic respiratory failure. Extracorporeal carbon dioxide removal has been successfully attempted in cases of adult respiratory distress syndrome, with protective hypercapnic ventilatory strategy. Nowadays, it is reported that it was also effective in reducing intubation in AECOPD with hypercapnic respiratory failure. Despite the apparent need for more supporting evidence, efforts to improve efficacy of NIV have continued unabated. It is anticipated that these efforts will, over time, serve toprogressively decrease the risk of intubation and invasive mechanical ventilation in cases of AECOPD with acute respiratory failure. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

Impact of noninvasive ventilation (NIV) trial for various types of acute respiratory failure in the emergency department; decreased mortality and use of the ICU.

PubMed

Tomii, Keisuke; Seo, Ryutaro; Tachikawa, Ryo; Harada, Yuka; Murase, Kimihiko; Kaji, Reiko; Takeshima, Yoshimi; Hayashi, Michio; Nishimura, Takashi; Ishihara, Kyosuke

2009-01-01

Trial of noninvasive ventilation (NIV) in the emergency department (ED) for heterogeneous acute respiratory failure (ARF) has been optional and its clinical benefit unclear. We conducted a retrospective cohort study comparing between two periods, October 2001-September 2003 and October 2004-September 2006, i.e., before and after adopting an NIV-trial strategy in which NIV was applied in the ED to any noncontraindicated ARF patients needing ventilatory support and was then continued in the intermediate-care-unit. During these two periods, we retrieved cases of ARF treated either invasively or with NIV, and compared the patients' in-hospital mortalities and the length of ICU and intermediate-care-unit stay. Compared were 73 (invasive 56, NIV 17) and 125 cases (invasive 31, NIV 94) retrieved from 271 and 415 emergent admissions with proper pulmonary etiologies for mechanical ventilation, respectively. Of their respiratory failures, type (hypercapnic/non-hypercapnic, 0.97 vs. 0.98) and severity (pH 7.23 vs. 7.21 for hypercapnic; PaO(2)/FiO(2) 133 vs. 137 for non-hypercapnic) were similar, and the rate of predisposing etiologies was not significantly different. However, excluding those with recurrent aspiration pneumonia for whom NIV was mostly used as "ceiling" treatment, significant reductions in both overall in-hospital mortality (38%-19%, risk ratio 0.51, 95% CI 0.31-0.84), and median length of ICU and intermediate-care-unit stay (12 vs. 5 days, P<0.0001) were found. NIV-trial in the ED for all possible patients with ARF of pulmonary etiologies, excluding those with recurrent aspiration pneumonia, may reduce overall in-hospital mortality and ICU stays.

Increased putamen hypercapnic vasoreactivity in levodopa-induced dyskinesia.

PubMed

Jourdain, Vincent A; Schindlbeck, Katharina A; Tang, Chris C; Niethammer, Martin; Choi, Yoon Young; Markowitz, Daniel; Nazem, Amir; Nardi, Dominic; Carras, Nicholas; Feigin, Andrew; Ma, Yilong; Peng, Shichun; Dhawan, Vijay; Eidelberg, David

2017-10-19

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.

Seven Passive 1-h Hypoxia Exposures Do Not Prevent AMS in Susceptible Individuals.

PubMed

Faulhaber, Martin; Pocecco, Elena; Gatterer, Hannes; Niedermeier, Martin; Huth, Maike; Dünnwald, Tobias; Menz, Verena; Bernardi, Luciano; Burtscher, Martin

2016-12-01

The present study evaluated the effects of a preacclimatization program comprising seven passive 1-h exposures to 4500-m normobaric hypoxia on the prevalence and severity of acute mountain sickness (AMS) during a subsequent exposure to real high altitude in persons susceptible to AMS. The project was designed as a randomized controlled trial including 32 healthy female and male participants with known susceptibility to AMS symptoms. After baseline measurements, participants were randomly assigned to the hypoxia or the control group to receive the preacclimatization program (seven passive 1-h exposures within 7 d to normobaric hypoxia or sham hypoxia). After completing preacclimatization, participants were transported (bus, cog railway) to real high altitude (3650 m, Mönchsjoch Hut, Switzerland) and stayed there for 45 h (two nights). Symptoms of AMS and physiological responses were determined repeatedly. AMS incidence and severity did not significantly differ between groups during the high-altitude exposure. In total, 59% of the hypoxia and 67% of the control group suffered from AMS at one or more time points during the high-altitude exposure. Hypoxic and hypercapnic ventilatory responses were not affected by the preacclimatization program. Resting ventilation at high altitude tended to be higher (P = 0.06) in the hypoxia group compared with the control group. No significant between-group differences were detected for heart rate variability, arterial oxygen saturation, and hematological and ventilatory parameters during the high-altitude exposure. Preacclimatization using seven passive 1-h exposures to normobaric hypoxia corresponding to 4500 m did not prevent AMS development during a subsequent high-altitude exposure in AMS-susceptible persons.

Cardiorespiratory effects of gap junction blockade in the locus coeruleus in unanesthetized adult rats.

PubMed

Patrone, Luis G A; Bícego, Kênia Cardoso; Hartzler, Lynn K; Putnam, Robert W; Gargaglioni, Luciane H

2014-01-01

The locus coeruleus (LC) plays an important role in central chemoreception. In young rats (P9 or younger), 85% of LC neurons increase firing rate in response to hypercapnia vs. only about 45% of neurons from rats P10 or older. Carbenoxolone (CARB - gap junction blocker) does not affect the % of LC neurons responding in young rats but it decreases the % responding by half in older animals. We evaluated the participation of gap junctions in the CO2 ventilatory response in unanesthetized adult rats by bilaterally microinjecting CARB (300μM, 1mM or 3mM/100nL), glycyrrhizic acid (GZA, CARB analog, 3mM) or vehicle (aCSF - artificial cerebrospinal fluid) into the LC of Wistar rats. Bilateral gap junction blockade in LC neurons did not affect resting ventilation; however, the increase in ventilation produced by hypercapnia (7% CO2) was reduced by ∼25% after CARB 1mM or 3mM injection (1939.7±104.8mLkg(-1)min(-1) for the aCSF group and 1468.3±122.2mLkg(-1)min(-1) for 1mM CARB, P<0.05; 1939.7±104.8mLkg(-1)min(-1) for the aCSF group and 1540.9±68.4mLkg(-1)min(-1) for the 3mM CARB group, P<0.05) due largely to a decrease in respiratory frequency. GZA injection or CARB injection outside the LC (peri-LC) had no effect on ventilation under any conditions. The results suggest that gap junctions in the LC modulate the hypercapnic ventilatory response of adult rats. Copyright © 2013 Elsevier B.V. All rights reserved.

Mechanisms of breathing instability in patients with obstructive sleep apnea.

PubMed

Younes, Magdy; Ostrowski, Michele; Atkar, Raj; Laprairie, John; Siemens, Andrea; Hanly, Patrick

2007-12-01

The response to chemical stimuli (chemical responsiveness) and the increases in respiratory drive required for arousal (arousal threshold) and for opening the airway without arousal (effective recruitment threshold) are important determinants of ventilatory instability and, hence, severity of obstructive apnea. We measured these variables in 21 obstructive apnea patients (apnea-hypopnea index 91 +/- 24 h(-1)) while on continuous-positive-airway pressure. During sleep, pressure was intermittently reduced (dial down) to induce severe hypopneas. Dial downs were done on room air and following approximately 30 s of breathing hypercapneic and/or hypoxic mixtures, which induced a range of ventilatory stimulation before dial down. Ventilation just before dial down and flow during dial down were measured. Chemical responsiveness, estimated as the percent increase in ventilation during the 5(th) breath following administration of 6% CO(2) combined with approximately 4% desaturation, was large (187 +/- 117%). Arousal threshold, estimated as the percent increase in ventilation associated with a 50% probability of arousal, ranged from 40% to >268% and was <120% in 12/21 patients, indicating that in many patients arousal occurs with modest changes in chemical drive. Effective recruitment threshold, estimated as percent increase in pre-dial-down ventilation associated with a significant increase in dial-down flow, ranged from zero to >174% and was <110% in 12/21 patients, indicating that in many patients reflex dilatation occurs with modest increases in drive. The two thresholds were not correlated. In most OSA patients, airway patency may be maintained with only modest increases in chemical drive, but instability results because of a low arousal threshold and a brisk increase in drive following brief reduction in alveolar ventilation.

Intact nitric oxide production is obligatory for the sustained flow response during hypercapnic acidosis in guinea pig heart.

PubMed

Heintz, Anke; Koch, Thea; Deussen, Andreas

2005-04-01

The mechanisms underlying hypercapnic coronary dilation remain unsettled. This study tests the hypothesis that flow dependent NO production is obligatory for the hypercapnic flow response. In isolated, constant pressure (CP) perfused guinea pig hearts a step change of arterial pCO(2) from 38.6 to 61.4 mm Hg induced a bi-phasic flow response with an early transient (maximum 60 s) and a consecutive persisting flow rise (121.6+/-6.6 (S.D.) % after 10 min). In contrast, when perfused with constant flow (CF), perfusion pressure only transiently (2 min) fell by 7.4+/-4.8 % following the step change of arterial pCO(2). In CP perfused hearts L-NAME (100 micromol/l) specifically abolished the delayed flow rise during hypercapnic acidosis (102.37+/-2.9% after 10 min), whereas the inhibitor had no effect on perfusion pressure response in CF perfused hearts. Under CP perfusion arterial hypercapnia resulted in a transient rise of coronary cGMP release (from 0.69+/-0.35 to 1.12+/-0.68 pmol/ml), which was abolished after L-NAME. Surprisingly, the K(+)ATP channel blocker glibenclamide did not have any significant effect on the hypercapnic flow response but largely blunted reactive hyperemia after a 20 s flow stop. The delayed steady state hypercapnic flow response in guinea pig heart requires intact NO production. The absence of a persisting decrease in coronary resistance under CF perfusion points to an important role of shear stress dependent NO production.

Effect of ageing on hypoxic exercise cardiorespiratory, muscle and cerebral oxygenation responses in healthy humans.

PubMed

Puthon, Lara; Bouzat, Pierre; Robach, Paul; Favre-Juvin, Anne; Doutreleau, Stéphane; Verges, Samuel

2017-04-01

What is the central question of this study? This study aimed to determine the effect of ageing on cardiorespiratory and tissue oxygenation responses to hypoxia during maximal incremental exercise. What is the main finding and its importance? Older healthy subjects had preserved hypoxic cardiorespiratory and tissue oxygenation responses at rest and during moderate exercise. At maximal exercise, they had a reduced hypoxic ventilatory response but similar maximal power output reduction compared with young individuals. This study suggests that until moderate exercise, hypoxic responses are preserved until the age of 70 years and therefore that ageing is not a contraindication for high-altitude sojourn. This study assessed the effects of ageing on cardiorespiratory and tissue oxygenation responses to hypoxia both at rest and during incremental maximal exercise. Sixteen young (20-30 years old) and 15 older healthy subjects (60-70 years old) performed two maximal incremental cycling tests in normoxia and hypoxia (inspiratory oxygen fraction 12%). Cardiorespiratory responses, prefrontal cortex and quadriceps tissue oxygenation (near-infrared spectroscopy) were measured during exercise as well as during hypercapnia at rest. The hypoxic ventilatory response was similar in young compared with older individuals at rest and during moderate-intensity exercise (50% maximal power output: young 0.9 ± 0.2 versus older 1.1 ± 0.8 l min -1  % -1 ; P > 0.05) but larger in young subjects during high-intensity exercise (maximal power output: 2.2 ± 0.8 versus 1.8 ± 1.1 l min -1  % -1 ; P < 0.05). The hypoxic cardiac response did not differ between groups both at rest and during exercise. During exercise in hypoxia, young subjects showed greater deoxygenation than older subjects, at both the prefrontal cortex and quadriceps levels. The hypoxia-induced reduction in maximal power output (young -32 ± 5% versus older -30 ± 6%; P > 0.05) and the hypercapnic responses did not differ between groups. Older healthy and active individuals below the age of 70 years have cardiorespiratory and tissue oxygenation responses to hypoxia similar to young individuals both at rest and during moderate-intensity exercise. Despite a lower hypoxic ventilatory response at maximal exercise, older individuals have similar oxygen desaturation and maximal power output reduction compared with young subjects. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Breath-to-breath hypercapnic response in neonatal rats: temperature dependency of the chemoreflexes and potential implications for breathing stability.

PubMed

Cummings, Kevin J; Frappell, Peter B

2009-07-01

The breathing of newborns is destabilized by warm temperatures. We hypothesized that in unanesthetized, intact newborn rats, body temperature (T(B)) influences the peripheral chemoreflex response (PCR response) to hypercapnia. To test this, we delivered square-wave challenges of 8% CO(2) in air to postnatal day 4-5 (P4-P5) rats held at a T(B) of 30 degrees C (Cold group, n = 11), 33 degrees C (Cool group, n = 10), and 35 degrees C thermoneutral zone group [thermoneutral zone (TNZ) group, n = 11], while measuring ventilation (Ve) directly with a pneumotach and mask. Cool animals were challenged with 8% CO(2) balanced in either air or hyperoxia (n = 10) to identify the PCR response. Breath-to-breath analysis was performed on 30 room air breaths and every breath of the 1-min CO(2) challenge. As expected, warmer T(B) was associated with an unstable breathing pattern in room air: TNZ animals had a coefficient of variation in Ve (Ve CV%) that was double that of animals held at cooler T(B) (P < 0.001). Hyperoxia markedly suppressed the hypercapnic ventilatory response over the first 10 breaths (or approximately 4 s), suggesting that this domain is dominated by the PCR response. The PCR response (P = 0.03) and total response (P = 0.04) were significantly greater in TNZ animals compared with hypothermic animals. The total response had a significant, negative relationship with Vco(2) (R(2) = 0.53; P < 0.001). Breathing stability was positively related to the total response (R(2) = 0.36; P < 0.001) and to a lesser extent, the PCR response (R(2) = 0.19; P = 0.01) and was negatively related to Vco(2) (R(2) = 0.34; P < 0.001). ANCOVA confirmed a significant effect of T(B) alone on breathing stability (P < 0.01), with no independent effects of Vco(2) (P = 0.41), the PCR response (P = 0.82), or the total Ve response (P = 0.08). Our data suggest that in early postnatal life, the chemoreflex responses to CO(2) are highly influenced by T(B), and while related to breathing stability, are not predictors of stability after accounting for the independent effect of T(B).

Persistent lung oscillator response to CO2 after buccal oscillator inhibition in the adult frog.

PubMed

Leclère, Renaud; Straus, Christian; Similowski, Thomas; Bodineau, Laurence; Fiamma, Marie-Noëlle

2012-08-15

The automatic ventilatory drive in amphibians depends on two oscillators interacting with each other, the gill/buccal and lung oscillators. The lung oscillator would be homologous to the mammalian pre-Bötzinger complex and the gill/buccal oscillator homologous to the mammalian parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN). Dysfunction of the pFRG/RTN has been involved in the development of respiratory diseases associated to the loss of CO(2) chemosensitivity such as the congenital central hypoventilation syndrome. Here, on adult in vitro isolated frog brainstem, consequences of the buccal oscillator inhibition (by reducing Cl(-)) were evaluated on the respiratory rhythm developed by the lung oscillator under hypercapnic challenges. Our results show that under low Cl(-) concentration (i) the buccal oscillator is strongly inhibited and the lung burst frequency and amplitude decreased and (ii) it persists a powerful CO(2) chemosensitivity. In conclusion, in frog, the CO(2) chemosensitivity depends on cellular contingent(s) whose the functioning is independent of the concentration of Cl(-) and origin remains unknown. Copyright © 2012 Elsevier B.V. All rights reserved.

Effectiveness and safety of noninvasive positive-pressure ventilation for severe hypercapnic encephalopathy due to acute exacerbation of chronic obstructive pulmonary disease: a prospective case-control study.

PubMed

Zhu, Guang-fa; Zhang, Wei; Zong, Hua; Xu, Qiu-fen; Liang, Ying

2007-12-20

Although severe encephalopathy has been proposed as a possible contraindication to the use of noninvasive positive-pressure ventilation (NPPV), increasing clinical reports showed it was effective in patients with impaired consciousness and even coma secondary to acute respiratory failure, especially hypercapnic acute respiratory failure (HARF). To further evaluate the effectiveness and safety of NPPV for severe hypercapnic encephalopathy, a prospective case-control study was conducted at a university respiratory intensive care unit (RICU) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) during the past 3 years. Forty-three of 68 consecutive AECOPD patients requiring ventilatory support for HARF were divided into 2 groups, which were carefully matched for age, sex, COPD course, tobacco use and previous hospitalization history, according to the severity of encephalopathy, 22 patients with Glasgow coma scale (GCS) < 10 served as group A and 21 with GCS = 10 as group B. Compared with group B, group A had a higher level of baseline arterial partial CO2 pressure ((102 +/- 27) mmHg vs (74 +/- 17) mmHg, P < 0.01), lower levels of GCS (7.5 +/- 1.9 vs 12.2 +/- 1.8, P < 0.01), arterial pH value (7.18 +/- 0.06 vs 7.28 +/- 0.07, P < 0.01) and partial O(2) pressure/fraction of inspired O(2) ratio (168 +/- 39 vs 189 +/- 33, P < 0.05). The NPPV success rate and hospital mortality were 73% (16/22) and 14% (3/22) respectively in group A, which were comparable to those in group B (68% (15/21) and 14% (3/21) respectively, all P > 0.05), but group A needed an average of 7 cm H2O higher of maximal pressure support during NPPV, and 4, 4 and 7 days longer of NPPV time, RICU stay and hospital stay respectively than group B (P < 0.05 or P < 0.01). NPPV therapy failed in 12 patients (6 in each group) because of excessive airway secretions (7 patients), hemodynamic instability (2), worsening of dyspnea and deterioration of gas exchange (2), and gastric content aspiration (1). Selected patients with severe hypercapnic encephalopathy secondary to HARF can be treated as effectively and safely with NPPV as awake patients with HARF due to AECOPD; a trial of NPPV should be instituted to reduce the need of endotracheal intubation in patients with severe hypercapnic encephalopathy who are otherwise good candidates for NPPV due to AECOPD.

Crayfish respiration as a function of water oxygenation.

PubMed

Dejours, P; Beekenkamp, H

1977-06-01

Crayfish, Astacus leptodactylus, for several hours breathed water equilibrated either with a hypoxic gas mixture, or air, or oxygen. The hydrostatic pressure in the right epibranchial cavity was recorded and the left epibranchial water sempled from time to time. The higher the water oxygenation, the less the duration of ventilation, the frequency of the scaphognathite beats which ensure water convection, the negative of the water hydrostatic pressure relative to ambient water pressure, and the respired water flow. The water convection per unit quantity of oxygen consumed decreased by a factor of about 20 when the animal passed from hypoxic water at PO2 of 72 torr to hyperoxic water at PO2 of 697 torr. Prolonged hyperoxia, up to 100 days, results in a hypercapnic acidosis of the prebranchial blood. pH decreased about 0.2 unit, PCO2 increased from 2.5 torr to a value of 6 torr, and [HCO-3] from 6 to a value of 9 meq-L-1. This hypercapnic acidosis remained uncompensated during several weeks exposure to hyperoxia. Observations on the fresh water crayfish, a marine crab, and several species of fish, suggest that in aquatic animals (1) the ventilatory activity depends greatly on the degree of water oxygenation: the higher the water oxygenation, the lower the ventilation; (2) the change of ventilation may be accompanied by a new equilibrium of the blood acid-base status, quite different from that observed in normoxia.

Respiratory muscle activity and patient–ventilator asynchrony during different settings of noninvasive ventilation in stable hypercapnic COPD: does high inspiratory pressure lead to respiratory muscle unloading?

PubMed Central

Duiverman, Marieke L; Huberts, Anouk S; van Eykern, Leo A; Bladder, Gerrie; Wijkstra, Peter J

2017-01-01

Introduction High-intensity noninvasive ventilation (NIV) has been shown to improve outcomes in stable chronic obstructive pulmonary disease patients. However, there is insufficient knowledge about whether with this more controlled ventilatory mode optimal respiratory muscle unloading is provided without an increase in patient–ventilator asynchrony (PVA). Patients and methods Ten chronic obstructive pulmonary disease patients on home mechanical ventilation were included. Four different ventilatory settings were investigated in each patient in random order, each for 15 min, varying the inspiratory positive airway pressure and backup breathing frequency. With surface electromyography (EMG), activities of the intercostal muscles, diaphragm, and scalene muscles were determined. Furthermore, pressure tracings were derived simultaneously in order to assess PVA. Results Compared to spontaneous breathing, the most pronounced decrease in EMG activity was achieved with the high-pressure settings. Adding a high breathing frequency did reduce EMG activity per breath, while the decrease in EMG activity over 1 min was comparable with the high-pressure, low-frequency setting. With high backup breathing frequencies less breaths were pressure supported (25% vs 97%). PVAs occurred more frequently with the low-frequency settings (P=0.017). Conclusion High-intensity NIV might provide optimal unloading of respiratory muscles, without undue increases in PVA. PMID:28138234

Respiratory muscle activity and patient-ventilator asynchrony during different settings of noninvasive ventilation in stable hypercapnic COPD: does high inspiratory pressure lead to respiratory muscle unloading?

PubMed

Duiverman, Marieke L; Huberts, Anouk S; van Eykern, Leo A; Bladder, Gerrie; Wijkstra, Peter J

2017-01-01

High-intensity noninvasive ventilation (NIV) has been shown to improve outcomes in stable chronic obstructive pulmonary disease patients. However, there is insufficient knowledge about whether with this more controlled ventilatory mode optimal respiratory muscle unloading is provided without an increase in patient-ventilator asynchrony (PVA). Ten chronic obstructive pulmonary disease patients on home mechanical ventilation were included. Four different ventilatory settings were investigated in each patient in random order, each for 15 min, varying the inspiratory positive airway pressure and backup breathing frequency. With surface electromyography (EMG), activities of the intercostal muscles, diaphragm, and scalene muscles were determined. Furthermore, pressure tracings were derived simultaneously in order to assess PVA. Compared to spontaneous breathing, the most pronounced decrease in EMG activity was achieved with the high-pressure settings. Adding a high breathing frequency did reduce EMG activity per breath, while the decrease in EMG activity over 1 min was comparable with the high-pressure, low-frequency setting. With high backup breathing frequencies less breaths were pressure supported (25% vs 97%). PVAs occurred more frequently with the low-frequency settings ( P =0.017). High-intensity NIV might provide optimal unloading of respiratory muscles, without undue increases in PVA.

[Analogies between heart and respiratory muscle failure. Importance to clinical practice].

PubMed

Köhler, D

2009-01-01

Heart failure is an established diagnosis. Respiratory muscle or ventilatory pump failure, however, is less well known. The latter becomes obvious through hypercapnia, caused by hypoventilation. The respiratory centre tunes into hypercapnea in order to prevent the danger of respiratory muscle overload (hypercapnic ventilatory failure). Hypoventilation will consecutively cause hypoxemia but this will not be responsible for performance limitation. One therefore has to distinguish primary hypoxemia evolving from diseases in the lung parenchyma. Here hypoxemia is the key feature and compensatory hyperventilation usually decreases PaCO2 levels. The cardiac as well as the respiratory pump adapt to an inevitable burden caused by chronic disease. In either case organ muscle mass will increase. If the burden exceeds the range of possible physiological adaptation, compensatory mechanisms will set in that are similar in both instances. During periods of overload either muscle system is mainly fueled by muscular glycogen. In the recovery phase (e. g. during sleep) stores are replenished, which can be recognized by down-regulation of the blood pressure in case of the cardiac pumb or by augmentation of hypercapnia through hypoventilation in case of the respiratory pump. The main function of cardiac and respiratory pump is maintenance of oxygen transport. The human body has developed certain compensatory mechanisms to adapt to insufficient oxygen supply especially during periods of overload. These mechanisms include shift of the oxygen binding curve, expression of respiratory chain isoenzymes capable of producing ATP at lower partial pressures of oxygen and the development of polyglobulia. Medically or pharmacologically the cardiac pump can be unloaded with beta blockers, the respiratory pump by application of inspired oxygen. Newer forms of therapy augment the process of recovery. The heart can be supported through bypass surgery or intravascular pump systems, while respiratory muscles may be supported through elective ventilatory support (mainly non-invasive) in the patient's home. The latter treatment in particular will increase patient endurance and quality of life and decrease mortality. Heart and respiratory pump failure share many common features. Since both take care of oxygen supply to the body, their function and compensatory mechanisms are closely related and linked.

Diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities in congenital central hypoventilation syndrome.

PubMed

Kumar, Rajesh; Macey, Paul M; Woo, Mary A; Alger, Jeffry R; Harper, Ronald M

2008-09-01

Congenital central hypoventilation syndrome (CCHS) patients show reduced breathing drive during sleep, decreased hypoxic and hypercapnic ventilatory responses, and autonomic and affective deficits, suggesting both brainstem and forebrain injuries. Forebrain damage was previously described in CCHS, but methodological limitations precluded detection of brainstem injury, a concern because genetic mutations in CCHS target brainstem autonomic nuclei. To assess brainstem and cerebellar areas, we used diffusion tensor imaging-based measures, namely axial diffusivity, reflecting water diffusion parallel to fibers, and sensitive to axonal injury, and radial diffusivity, measuring diffusion perpendicular to fibers, and indicative of myelin injury. Diffusion tensor imaging was performed in 12 CCHS and 26 controls, and axial and radial diffusivity maps were compared between groups using analysis of covariance (covariates; age and gender). Increased axial diffusivity in CCHS appeared within the lateral medulla and clusters with injury extended from the dorsal midbrain through the periaqueductal gray, raphé, and superior cerebellar decussation, ventrally to the basal-pons. Cerebellar cortex and deep nuclei, and the superior and inferior cerebellar peduncles showed increased radial diffusivity. Midbrain, pontine, and lateral medullary structures, and the cerebellum and its fiber systems are injured in CCHS, likely contributing to the characteristics found in the syndrome.

Forced vital capacity and not central chemoreflex predicts maximal hyperoxic breath-hold duration in elite apneists.

PubMed

Bain, Anthony R; Barak, Otto F; Hoiland, Ryan L; Drvis, Ivan; Bailey, Damian M; Dujic, Zeljko; Mijacika, Tanja; Santoro, Antoinette; DeMasi, Daniel K; MacLeod, David B; Ainslie, Philip N

2017-08-01

The determining mechanisms of a maximal hyperoxic apnea duration in elite apneists have remained unexplored. We tested the hypothesis that maximal hyperoxic apnea duration in elite apneists is related to forced vital capacity (FVC) but not the central chemoreflex (for CO 2 ). Eleven elite apneists performed a maximal dry static-apnea with prior hyperoxic (100% oxygen) pre-breathing, and a central chemoreflex test via a hyperoxic re-breathing technique (hyperoxic-hypercapnic ventilatory response: HCVR); expressed as the increase in ventilation (pneumotachometry) per increase in arterial CO 2 tension (PaCO 2 ; radial artery). FVC was assessed using standard spirometry. Maximal apnea duration ranged from 807 to 1262s (mean=1034s). Average HCVR was 2.0±1.2Lmin -1 mmHg -1 PaCO 2 . The hyperoxic apnea duration was related to the FVC (r 2 =0.45, p<0.05), but not the HCVR (r 2 <0.01, p>0.05). These findings were interpreted to suggest that during a hyperoxic apnea, a larger initial lung volume prolongs the time before reaching intolerable discomfort associated with pending lung squeeze, while CO 2 sensitivity has little impact. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Chronic Sleep Fragmentation on Wake-Active Neurons and the Hypercapnic Arousal Response

PubMed Central

Li, Yanpeng; Panossian, Lori A.; Zhang, Jing; Zhu, Yan; Zhan, Guanxia; Chou, Yu-Ting; Fenik, Polina; Bhatnagar, Seema; Piel, David A.; Beck, Sheryl G.; Veasey, Sigrid

2014-01-01

Study Objectives: Delayed hypercapnic arousals may occur in obstructive sleep apnea. The impaired arousal response is expected to promote more pronounced oxyhemoglobin desaturations. We hypothesized that long-term sleep fragmentation (SF) results in injury to or dysfunction of wake-active neurons that manifests, in part, as a delayed hypercapnic arousal response. Design: Adult male mice were implanted for behavioral state recordings and randomly assigned to 4 weeks of either orbital platform SF (SF4wk, 30 events/h) or control conditions (Ct4wk) prior to behavioral, histological, and locus coeruleus (LC) whole cell electrophysiological evaluations. Measurements and Results: SF was successfully achieved across the 4 week study, as evidenced by a persistently increased arousal index, P < 0.01 and shortened sleep bouts, P < 0.05, while total sleep/wake times and plasma corticosterone levels were unaffected. A multiple sleep latency test performed at the onset of the dark period showed a reduced latency to sleep in SF4wk mice (P < 0.05). The hypercapnic arousal latency was increased, Ct4wk 64 ± 5 sec vs. SF4wk 154 ± 6 sec, P < 0.001, and remained elevated after a 2 week recovery (101 ± 4 sec, P < 0.001). C-fos activation in noradrenergic, orexinergic, histaminergic, and cholinergic wake-active neurons was reduced in response to hypercapnia (P < 0.05-0.001). Catecholaminergic and orexinergic projections into the cingulate cortex were also reduced in SF4wk (P < 0.01). In addition, SF4wk resulted in impaired LC neuron excitability (P < 0.01). Conclusions: Four weeks of sleep fragmentation (SF4wk) impairs arousal responses to hypercapnia, reduces wake neuron projections and locus coeruleus neuronal excitability, supporting the concepts that some effects of sleep fragmentation may contribute to impaired arousal responses in sleep apnea, which may not reverse immediately with therapy. Citation: Li Y; Panossian LA; Zhang J; Zhu Y; Zhan G; Chou YT; Fenik P; Bhatnagar S; Piel DA; Beck SG; Veasey S. Effects of chronic sleep fragmentation on wake-active neurons and the hypercapnic arousal response. SLEEP 2014;37(1):51-64. PMID:24470695

Upper airway CO2 receptors in tegu lizards: localization and ventilatory sensitivity.

PubMed

Coates, E L; Ballam, G O

1987-01-01

1. Tidal volume, end-tidal CO2, and ventilatory frequency in Tupinambis nigropunctatus were measured in response to CO2 (1-4%) delivered to either the mouth or nares. Additionally, the sensitivity of the ventilatory response to nasal CO2 was evaluated at CO2 concentrations less than 1%. The ventilatory parameters were also measured in response to CO2 (1-4%) delivered to the nares after the olfactory peduncle was transected. 2. It was found that (0.4-4%) nasal CO2 depressed ventilatory frequency by 9% to 83% respectively, while tidal volume was not significantly altered. CO2 (1-4%) delivered to the mouth produced no apparent changes in any of the ventilatory parameters. Following transection of the olfactory peduncle, nasal CO2 was ineffective in producing any change in ventilatory frequency or depth. 3. These findings indicate that CO2-sensitive receptors are located in either the nasal or vomeronasal membranes of tegu lizards and that the olfactory peduncle must be intact for these receptors to affect ventilatory changes in response to elevated CO2 concentrations. The receptors are capable of mediating a ventilatory response to CO2 concentrations lower than those found in either expired air or in confined spaces such as occupied burrows. 4. The discrepancies in the ventilatory responses of lizards and snakes to inspired CO2 reported in past experiments may be partially explained by the presence of nasal or vomeronasal CO2-sensitive receptors.

Diphtheria toxin treatment of Pet-1-Cre floxed diphtheria toxin receptor mice disrupts thermoregulation without affecting respiratory chemoreception.

PubMed

Cerpa, V; Gonzalez, A; Richerson, G B

2014-10-24

In genetically-modified Lmx1b(f/f/p) mice, selective deletion of LMX1B in Pet-1 expressing cells leads to failure of embryonic development of serotonin (5-HT) neurons. As adults, these mice have a decreased hypercapnic ventilatory response and abnormal thermoregulation. This mouse model has been valuable in defining the normal role of 5-HT neurons, but it is possible that developmental compensation reduces the severity of observed deficits. Here we studied mice genetically modified to express diphtheria toxin receptors (DTR) on Pet-1 expressing neurons (Pet-1-Cre/floxed DTR or Pet1/DTR mice). These mice developed with a normal complement of 5-HT neurons. As adults, systemic treatment with 2-35μg of diphtheria toxin (DT) reduced the number of tryptophan hydroxylase-immunoreactive (TpOH-ir) neurons in the raphe nuclei and ventrolateral medulla by 80%. There were no effects of DT on minute ventilation (VE) or the ventilatory response to hypercapnia or hypoxia. At an ambient temperature (TA) of 24°C, all Pet1/DTR mice dropped their body temperature (TB) below 35°C after DT treatment, but the latency was shorter in males than females (3.0±0.37 vs. 4.57±0.29days, respectively; p<0.001). One week after DT treatment, mice were challenged by dropping TA from 37°C to 24°C, which caused TB to decrease more in males than in females (29.7±0.31°C vs. 33.0±1.3°C, p<0.01). We conclude that the 20% of 5-HT neurons that remain after DT treatment in Pet1/DTR mice are sufficient to maintain normal baseline breathing and a normal response to CO2, while those affected include some essential for thermoregulation, in males more than females. In comparison to models with deficient embryonic development of 5-HT neurons, acute deletion of 5-HT neurons in adults leads to a greater defect in thermoregulation, suggesting that significant developmental compensation can occur. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Breathing regulation and blood gas homeostasis after near complete lesions of the retrotrapezoid nucleus in adult rats.

PubMed

Souza, George M P R; Kanbar, Roy; Stornetta, Daniel S; Abbott, Stephen B G; Stornetta, Ruth L; Guyenet, Patrice G

2018-04-18

The retrotrapezoid nucleus (RTN) is one of several CNS nuclei that contribute, in various capacities (e.g. CO 2 detection, neuronal modulation) to the central respiratory chemoreflex (CRC). Here we test how important the RTN is to PCO 2 homeostasis and breathing during sleep or wake. RTN Nmb positive neurons were killed with targeted microinjections of substance-P-saporin conjugate in adult rats. Under normoxia, rats with large RTN lesions (92 ± 4 % cell loss) had normal blood pressure (BP) and arterial pH but were hypoxic (-8 mmHg PaO 2 ) and hypercapnic (+10 mmHg PaCO 2 ). In resting conditions, minute-volume (V E ) was normal but breathing frequency (f R ) was elevated and tidal volume (V T ) reduced. Resting O 2 consumption and CO 2 production were normal. The hypercapnic ventilatory reflex in 65% FiO 2 had an inverse exponential relationship with the number of surviving RTN neurons and was decreased by up to 92%. The hypoxic ventilatory reflex (HVR; FiO 2 21-10%) persisted after RTN lesions, hypoxia-induced sighing was normal and hypoxia-induced hypotension reduced. In rats with RTN lesions, breathing was lowest during slow-wave sleep (SWS), especially under hyperoxia, but apneas and sleep-disordered breathing were not observed. In conclusion, near complete RTN destruction in rats virtually eliminates the CRC but HVR persists and sighing and the state-dependence of breathing are unchanged. Under normoxia, RTN lesions cause no change in V E but alveolar ventilation is reduced by at least 21%, probably because of increased physiological dead volume. RTN lesions do not cause sleep apnea during SWS, even under hyperoxia. Background: the retrotrapezoid nucleus (RTN) drives breathing proportionally to brain PCO 2 but its role during various states of vigilance needed clarification. New result: Under normoxia, RTN lesions increase the arterial PCO 2 set-point, lower the PO 2 set-point and reduce alveolar ventilation relative to CO 2 production. Tidal volume is reduced and breathing frequency increased to a comparable degree during wake, slow-wave sleep and REM sleep. RTN lesions do not produce apneas or disordered breathing during sleep. New result: RTN lesions in rats virtually eliminate the central respiratory chemoreflex (CRC) while preserving the cardiorespiratory responses to hypoxia; the relationship between CRC and number of surviving RTN Nmb neurons is an inverse exponential. the CRC does not function without the RTN. In the quasi-complete absence of the RTN and CRC, alveolar ventilation is reduced despite an increased drive to breathe from the carotid bodies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Central sleep apnea syndrome].

PubMed

Sanner, B; Schäfer, T

2008-04-01

Central sleep apnea (CSA) is characterized by a lack of drive to inspire for at least 10 sec. In the CSA-syndrome accompanying arousals and desaturations of the arterial blood cause sleep disturbances and sympathetic nerve activations which lead to excessive daytime sleepiness and increase the risk for cardiovascular morbidity. There are six manifestations of CSA: a rare primary or idiopathic form, often in hypocapnic patients with an increased hypercapnic ventilatory drive; Cheyne-Stokes respiration, characterised by periodic CSA and a crescendo/decrescendo breathing pattern, often in patients with severe cardiac or neurological diseases; high altitude-induced periodic breathing (above 4000 m), CSA due to medical or neurological conditions; CSA due to drug or substance use; and primary sleep apnea of infancy. Besides the consequent treatment of the underlying medical conditions therapeutic options include the use of drugs, e. g. acetacolamide or oxygen, as well as non-invasive ventilation, e. g. continuous positive airway pressure (CPAP) or adaptive servo-ventilation.

Variable Inhibition by Falling CO2 of Hypoxic Ventilatory Response in Man,

DTIC Science & Technology

1983-06-21

alkalosis which, in turn, inhibits the ventilatory response to hypoxia (4,5,11). Thus for the usual measurement of the acute ventilatory response to...rest for 20 minutes. All of the ventilatory response tests were performed with the subject breathing through a respiratory valve (Model 2700, Hans...increase ventilation because the inhibition by hypocapnic alkalosis is prevented by adding CO2 to the inspired air to maintain C02 and pH at their

Influence of sympathoexcitation at high altitude on cerebrovascular function and ventilatory control in humans.

PubMed

Ainslie, P N; Lucas, S J E; Fan, J-L; Thomas, K N; Cotter, J D; Tzeng, Y C; Burgess, Keith R

2012-10-01

We sought to determine the influence of sympathoexcitation on dynamic cerebral autoregulation (CA), cerebrovascular reactivity, and ventilatory control in humans at high altitude (HA). At sea level (SL) and following 3-10 days at HA (5,050 m), we measured arterial blood gases, ventilation, arterial pressure, and middle cerebral blood velocity (MCAv) before and after combined α- and β-adrenergic blockade. Dynamic CA was quantified using transfer function analysis. Cerebrovascular reactivity was assessed using hypocapnia and hyperoxic hypercapnia. Ventilatory control was assessed from the hypercapnia and during isocapnic hypoxia. Arterial Pco(2) and ventilation and its control were unaltered following blockade at both SL and HA. At HA, mean arterial pressure (MAP) was elevated (P < 0.01 vs. SL), but MCAv remained unchanged. Blockade reduced MAP more at HA than at SL (26 vs. 15%, P = 0.048). At HA, gain and coherence in the very-low-frequency (VLF) range (0.02-0.07 Hz) increased, and phase lead was reduced (all P < 0.05 vs. SL). Following blockade at SL, coherence was unchanged, whereas VLF phase lead was reduced (-40 ± 23%; P < 0.01). In contrast, blockade at HA reduced low-frequency coherence (-26 ± 20%; P = 0.01 vs. baseline) and elevated VLF phase lead (by 177 ± 238%; P < 0.01 vs. baseline), fully restoring these parameters back to SL values. Irrespective of this elevation in VLF gain at HA (P < 0.01), blockade increased it comparably at SL and HA (∼43-68%; P < 0.01). Despite elevations in MCAv reactivity to hypercapnia at HA, blockade reduced (P < 0.05) it comparably at SL and HA, effects we attributed to the hypotension and/or abolition of the hypercapnic-induced increase in MAP. With the exception of dynamic CA, we provide evidence of a redundant role of sympathetic nerve activity as a direct mechanism underlying changes in cerebrovascular reactivity and ventilatory control following partial acclimatization to HA. These findings have implications for our understanding of CBF function in the context of pathologies associated with sympathoexcitation and hypoxemia.

Ventilatory demand and dynamic hyperinflation induced during ADL-based tests in Chronic Obstructive Pulmonary Disease patients

PubMed Central

dos Santos, Karoliny; Gulart, Aline A.; Munari, Anelise B.; Karloh, Manuela; Mayer, Anamaria F.

2016-01-01

ABSTRACT Background Airflow limitation frequently leads to the interruption of activities of daily living (ADL) in patients with Chronic Obstructive Pulmonary Disease (COPD). These patients commonly show absence of ventilatory reserve, reduced inspiratory reserve volume, and dynamic hyperinflation (DH). Objective To investigate ventilatory response and DH induced by three ADL-based protocols in COPD patients and compare them to healthy subjects. Method Cross-sectional study. COPD group: 23 patients (65±6 years, FEV1 37.2±15.4%pred); control group: 14 healthy subjects (64±4 years) matched for age, sex, and body mass index. Both groups performed all three tests: Glittre-ADL test; an activity test that involved moving objects on a shelf (TSHELF); and a modified shelf protocol isolating activity with upper limbs (TSHELF-M). Ventilatory response and inspiratory capacity were evaluated. Results Baseline ventilatory variables were similar between groups (p>0.05). The ventilatory demand increased and the inspiratory capacity decreased significantly at the end of the tests in the COPD group. Ventilatory demand and DH were higher (p<0.05) in the TSHELF than in the TSHELF–M in the COPD group (p<0.05). There were no differences in DH between the three tests in the control group (p>0.05) and ventilatory demand increased at the end of the tests (p<0.05) but to a lower extent than the COPD group. Conclusion The TSHELF induces similar ventilatory responses to the Glittre-ADL test in COPD patients with higher ventilatory demand and DH. In contrast, the ventilatory response was attenuated in the TSHELF-M, suggesting that squatting and bending down during the Glittre-ADL test could trigger significant ventilatory overload. PMID:27333482

Increased ventilatory response to carbon dioxide in COPD patients following vitamin C administration

PubMed Central

Hartmann, Sara E.; Kissel, Christine K.; Szabo, Lian; Walker, Brandie L.; Leigh, Richard; Anderson, Todd J.

2015-01-01

Patients with chronic obstructive pulmonary disease (COPD) have decreased ventilatory and cerebrovascular responses to hypercapnia. Antioxidants increase the ventilatory response to hypercapnia in healthy humans. Cerebral blood flow is an important determinant of carbon dioxide/hydrogen ion concentration at the central chemoreceptors and may be affected by antioxidants. It is unknown whether antioxidants can improve the ventilatory and cerebral blood flow response in individuals in whom these are diminished. Thus, we aimed to determine the effect of vitamin C administration on the ventilatory and cerebrovascular responses to hypercapnia during healthy ageing and in COPD. Using transcranial Doppler ultrasound, we measured the ventilatory and cerebral blood flow responses to hyperoxic hypercapnia before and after an intravenous vitamin C infusion in healthy young (Younger) and older (Older) subjects and in moderate COPD. Vitamin C increased the ventilatory response in COPD patients (mean (95% CI) 1.1 (0.9–1.1) versus 1.5 (1.1–2.0) L·min−1·mmHg−1, p<0.05) but not in Younger (2.5 (1.9–3.1) versus 2.4 (1.9–2.9) L·min−1·mmHg−1, p>0.05) or Older (1.3 (1.0–1.7) versus 1.3 (1.0–1.7) L·min−1·mmHg−1, p>0.05) healthy subjects. Vitamin C did not affect the cerebral blood flow response in the young or older healthy subjects or COPD subjects (p>0.05). Vitamin C increases the ventilatory but not cerebrovascular response to hyperoxic hypercapnia in patients with moderate COPD. PMID:27730137

Ventilation and hypoxic ventilatory responsiveness in Chinese-Tibetan residents at 3,658 m.

PubMed

Curran, L S; Zhuang, J; Sun, S F; Moore, L G

1997-12-01

When breathing ambient air at rest at 3,658 m altitude, Tibetan lifelong residents of 3,658 m ventilate as much as newcomers acclimatized to high altitude; they also ventilate more and have greater hypoxic ventilatory responses (HVRs) than do Han ("Chinese") long-term residents at 3,658 m. This suggests that Tibetan ancestry is advantageous in protecting resting ventilation levels during years of hypoxic exposure and is of interest in light of the permissive role of hypoventilation in the development of chronic mountain sickness, which is nearly absent among Tibetans. The existence of individuals with mixed Tibetan-Chinese ancestry (Han-Tibetans) residing at 3,658 m affords an opportunity to test this hypothesis. Eighteen men born in Lhasa, Tibet, China (3,658 m) to Tibetan mothers and Han fathers were compared with 27 Tibetan men and 30 Han men residing at 3,658 m who were previously studied. We used the same study procedures (minute ventilation was measured with a dry-gas flowmeter during room air breathing and hyperoxia and with a 13-liter spirometer-rebreathing system during the hypoxic and hypercapnic tests). During room air breathing at 3,658 m (inspired O2 pressure = 93 Torr), Han-Tibetans resembled Tibetans in ventilation (12.1 +/- 0.6 vs. 11.5+/- 0.5 l/min BTPS, respectively) but had HVR that were blunted (63 +/- 16 vs. 121 +/- 13, respectively, for HVR shape parameter A) and declined with increasing duration of high-altitude residence. During administered hyperoxia (inspired O2 pressure = 310 Torr) at 3,658 m, the paradoxical hyperventilation previously seen in Tibetan but not Han residents at 3,658 m (11.8 +/- 0.5 vs. 10.1 +/- 0.5 l/min BTPS) was absent in these Han-Tibetans (9.8 +/- 0.6 l/min BTPS). Thus, although longer duration of high-altitude residence appears to progressively blunt HVR among Han-Tibetans born and residing at 3, 658 m, their Tibetan ancestry appears protective in their maintenance of high resting ventilation levels despite diminished chemosensitivity.

A novel perspective to calibrate temporal delays in cerebrovascular reactivity using hypercapnic and hyperoxic respiratory challenges.

PubMed

Champagne, Allen A; Bhogal, Alex A; Coverdale, Nicole S; Mark, Clarisse I; Cook, Douglas J

2017-12-05

Redistribution of blood flow across different brain regions, arising from the vasoactive nature of hypercapnia, can introduce errors when examining cerebrovascular reactivity (CVR) response delays. In this study, we propose a novel analysis method to characterize hemodynamic delays in the blood oxygen level dependent (BOLD) response to hypercapnia, and hyperoxia, as a way to provide insight into transient differences in vascular reactivity between cortical regions, and across tissue depths. A pseudo-continuous arterial spin labeling sequence was used to acquire BOLD and cerebral blood flow simultaneously in 19 healthy adults (12 F; 20 ± 2 years) during boxcar CO 2 and O 2 gas inhalation paradigms. Despite showing distinct differences in hypercapnia-induced response delay times (P < 0.05; Bonferroni corrected), grey matter regions showed homogenous hemodynamic latencies (P > 0.05) once calibrated for bolus arrival time derived using non-vasoactive hyperoxic gas challenges. Longer hypercapnic temporal delays were observed as the depth of the white matter tissue increased, although no significant differences in response lag were found during hyperoxia across tissue depth, or between grey and white matter. Furthermore, calibration of hypercapnic delays using hyperoxia revealed that deeper white matter layers may be more prone to dynamic redistribution of blood flow, which introduces response lag times ranging between 1 and 3 s in healthy subjects. These findings suggest that the combination of hypercapnic and hyperoxic gas-inhalation MRI can be used to distinguish between differences in CVR that arise as a result of delayed stimulus arrival time (due to the local architecture of the cerebrovasculature), or preferential blood flow distribution. Calibrated response delays to hypercapnia provide important insights into cerebrovascular physiology, and may be used to correct response delays associated with vascular impairment. Copyright © 2017. Published by Elsevier Inc.

Hypercapnic acidosis attenuates ventilation-induced lung injury by a nuclear factor-κB-dependent mechanism.

PubMed

Contreras, Maya; Ansari, Bilal; Curley, Gerard; Higgins, Brendan D; Hassett, Patrick; O'Toole, Daniel; Laffey, John G

2012-09-01

Hypercapnic acidosis protects against ventilation-induced lung injury. We wished to determine whether the beneficial effects of hypercapnic acidosis in reducing stretch-induced injury were mediated via inhibition of nuclear factor-κB, a key transcriptional regulator in inflammation, injury, and repair. Prospective randomized animal study. University research laboratory. Adult male Sprague-Dawley rats. In separate experimental series, the potential for hypercapnic acidosis to attenuate moderate and severe ventilation-induced lung injury was determined. In each series, following induction of anesthesia and tracheostomy, Sprague-Dawley rats were randomized to (normocapnia; FICO2 0.00) or (hypercapnic acidosis; FICO2 0.05), subjected to high stretch ventilation, and the severity of lung injury and indices of activation of the nuclear factor-κB pathway were assessed. Subsequent in vitro experiments examined the potential for hypercapnic acidosis to reduce pulmonary epithelial inflammation and injury induced by cyclic mechanical stretch. The role of the nuclear factor-κB pathway in hypercapnic acidosis-mediated protection from stretch injury was then determined. Hypercapnic acidosis attenuated moderate and severe ventilation-induced lung injury, as evidenced by improved oxygenation, compliance, and reduced histologic injury compared to normocapnic conditions. Hypercapnic acidosis reduced indices of inflammation such as interleukin-6 and bronchoalveolar lavage neutrophil infiltration. Hypercapnic acidosis reduced the decrement of the nuclear factor-κB inhibitor IκBα and reduced the generation of cytokine-induced neutrophil chemoattractant-1. Hypercapnic acidosis reduced cyclic mechanical stretch-induced nuclear factor-κB activation, reduced interleukin-8 production, and decreased epithelial injury and cell death compared to normocapnia. Hypercapnic acidosis attenuated ventilation-induced lung injury independent of injury severity and decreased mechanical stretch-induced epithelial injury and death, via a nuclear factor-κB-dependent mechanism.

Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats.

PubMed

Kaplan, Kara; Echert, Ashley E; Massat, Ben; Puissant, Madeleine M; Palygin, Oleg; Geurts, Aron M; Hodges, Matthew R

2016-05-01

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/-) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA(Tph2-/-) rats. Body temperature was also maintained in adult DA(Tph2-/-) rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA(Tph2-/-) rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. Copyright © 2016 the American Physiological Society.

Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats

PubMed Central

Kaplan, Kara; Echert, Ashley E.; Massat, Ben; Puissant, Madeleine M.; Palygin, Oleg; Geurts, Aron M.

2016-01-01

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DATph2−/−) rats. DATph2−/− rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DATph2−/− rats. Body temperature was also maintained in adult DATph2−/− rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DATph2−/− rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. PMID:26869713

Effects of chronic sleep fragmentation on wake-active neurons and the hypercapnic arousal response.

PubMed

Li, Yanpeng; Panossian, Lori A; Zhang, Jing; Zhu, Yan; Zhan, Guanxia; Chou, Yu-Ting; Fenik, Polina; Bhatnagar, Seema; Piel, David A; Beck, Sheryl G; Veasey, Sigrid

2014-01-01

Delayed hypercapnic arousals may occur in obstructive sleep apnea. The impaired arousal response is expected to promote more pronounced oxyhemoglobin desaturations. We hypothesized that long-term sleep fragmentation (SF) results in injury to or dysfunction of wake-active neurons that manifests, in part, as a delayed hypercapnic arousal response. Adult male mice were implanted for behavioral state recordings and randomly assigned to 4 weeks of either orbital platform SF (SF4wk, 30 events/h) or control conditions (Ct4wk) prior to behavioral, histological, and locus coeruleus (LC) whole cell electrophysiological evaluations. SF was successfully achieved across the 4 week study, as evidenced by a persistently increased arousal index, P < 0.01 and shortened sleep bouts, P < 0.05, while total sleep/wake times and plasma corticosterone levels were unaffected. A multiple sleep latency test performed at the onset of the dark period showed a reduced latency to sleep in SF4wk mice (P < 0.05). The hypercapnic arousal latency was increased, Ct4wk 64 ± 5 sec vs. SF4wk 154 ± 6 sec, P < 0.001, and remained elevated after a 2 week recovery (101 ± 4 sec, P < 0.001). C-fos activation in noradrenergic, orexinergic, histaminergic, and cholinergic wake-active neurons was reduced in response to hypercapnia (P < 0.05-0.001). Catecholaminergic and orexinergic projections into the cingulate cortex were also reduced in SF4wk (P < 0.01). In addition, SF4wk resulted in impaired LC neuron excitability (P < 0.01). Four weeks of sleep fragmentation (SF4wk) impairs arousal responses to hypercapnia, reduces wake neuron projections and locus coeruleus neuronal excitability, supporting the concepts that some effects of sleep fragmentation may contribute to impaired arousal responses in sleep apnea, which may not reverse immediately with therapy.

Estrogen attenuates the cardiovascular and ventilatory responses to central command in cats.

PubMed

Hayes, Shawn G; Moya Del Pino, Nicolas B; Kaufman, Marc P

2002-04-01

Static exercise is well known to increase heart rate, arterial blood pressure, and ventilation. These increases appear to be less in women than in men, a difference that has been attributed to an effect of estrogen on neuronal function. In decerebrate male cats, we examined the effect of estrogen (17beta-estradiol; 0.001, 0.01, 0.1, and 1.0 microg/kg iv) on the cardiovascular and ventilatory responses to central command and the exercise pressor reflex, the two neural mechanisms responsible for evoking the autonomic and ventilatory responses to exercise. We found that 17beta-estradiol, in each of the three doses tested, attenuated the pressor, cardioaccelerator, and phrenic nerve responses to electrical stimulation of the mesencephalic locomotor region (i.e., central command). In contrast, none of the doses of 17beta-estradiol had any effect on the pressor, cardioaccelerator, and ventilatory responses to static contraction or stretch of the triceps surae muscles. We conclude that, in decerebrate male cats, estrogen injected intravenously attenuates cardiovascular and ventilatory responses to central command but has no effect on responses to the exercise pressor reflex.

Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex

PubMed Central

Corcoran, Andrea E.; Brust, Rachael D.; Chang, YoonJeung; Nattie, Eugene E.

2017-01-01

Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 (Tac1) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1, referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine-N-oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO2. Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using genetic tools, we characterize a 5-HT neuron subtype defined by expression of Tachykinin1 and Pet1 (Tac1-Pet1 neurons), mapping soma localization to the caudal medulla primarily and axonal projections to brainstem motor nuclei most prominently, and, when silenced, observed blunting of the ventilatory response to inhaled CO2. Tac1-Pet1 neurons thus appear distinct from and contrast previously described Egr2-Pet1 neurons, which project primarily to chemosensory integration centers and are themselves chemosensitive. PMID:28073937

Ageing and cardiorespiratory response to hypoxia.

PubMed

Lhuissier, François J; Canouï-Poitrine, Florence; Richalet, Jean-Paul

2012-11-01

The risk of severe altitude-induced diseases is related to ventilatory and cardiac responses to hypoxia and is dependent on sex, age and exercise training status. However, it remains unclear how ageing modifies these physiological adaptations to hypoxia. We assessed the physiological responses to hypoxia with ageing through a cross-sectional 20 year study including 4675 subjects (2789 men, 1886 women; 14-85 years old) and a longitudinal study including 30 subjects explored at a mean 10.4 year interval. The influence of sex, training status and menopause was evaluated. The hypoxia-induced desaturation and the ventilatory and cardiac responses to hypoxia at rest and exercise were measured. In men, ventilatory response to hypoxia increased (P < 0.002), while desaturation was less pronounced (P < 0.001) with ageing. Cardiac response to hypoxia was blunted with ageing in both sexes (P < 0.001). Similar results were found in the longitudinal study, with a decrease in cardiac and an increase in ventilatory response to hypoxia with ageing. These adaptive responses were less pronounced or absent in post-menopausal women (P < 0.01). At exercise, desaturation was greater in trained subjects but cardiac and ventilatory responses to hypoxia were preserved by training, especially in elderly people. In conclusion, respiratory response to hypoxia and blood oxygenation improve with ageing in men while cardiac response is blunted with ageing in both sexes. Training aggravates desaturation at exercise in hypoxia, improves the ventilatory response and limits the ageing-induced blunting of cardiac response to hypoxia. Training limits the negative effects of menopause in cardiorespiratory adaptations to hypoxia.

Quantifying the ventilatory control contribution to sleep apnoea using polysomnography.

PubMed

Terrill, Philip I; Edwards, Bradley A; Nemati, Shamim; Butler, James P; Owens, Robert L; Eckert, Danny J; White, David P; Malhotra, Atul; Wellman, Andrew; Sands, Scott A

2015-02-01

Elevated loop gain, consequent to hypersensitive ventilatory control, is a primary nonanatomical cause of obstructive sleep apnoea (OSA) but it is not possible to quantify this in the clinic. Here we provide a novel method to estimate loop gain in OSA patients using routine clinical polysomnography alone. We use the concept that spontaneous ventilatory fluctuations due to apnoeas/hypopnoeas (disturbance) result in opposing changes in ventilatory drive (response) as determined by loop gain (response/disturbance). Fitting a simple ventilatory control model (including chemical and arousal contributions to ventilatory drive) to the ventilatory pattern of OSA reveals the underlying loop gain. Following mathematical-model validation, we critically tested our method in patients with OSA by comparison with a standard (continuous positive airway pressure (CPAP) drop method), and by assessing its ability to detect the known reduction in loop gain with oxygen and acetazolamide. Our method quantified loop gain from baseline polysomnography (correlation versus CPAP-estimated loop gain: n=28; r=0.63, p<0.001), detected the known reduction in loop gain with oxygen (n=11; mean±sem change in loop gain (ΔLG) -0.23±0.08, p=0.02) and acetazolamide (n=11; ΔLG -0.20±0.06, p=0.005), and predicted the OSA response to loop gain-lowering therapy. We validated a means to quantify the ventilatory control contribution to OSA pathogenesis using clinical polysomnography, enabling identification of likely responders to therapies targeting ventilatory control. Copyright ©ERS 2015.

Quantifying the ventilatory control contribution to sleep apnoea using polysomnography

PubMed Central

Terrill, Philip I.; Edwards, Bradley A.; Nemati, Shamim; Butler, James P.; Owens, Robert L.; Eckert, Danny J.; White, David P.; Malhotra, Atul; Wellman, Andrew; Sands, Scott A.

2015-01-01

Elevated loop gain, consequent to hypersensitive ventilatory control, is a primary nonanatomical cause of obstructive sleep apnoea (OSA) but it is not possible to quantify this in the clinic. Here we provide a novel method to estimate loop gain in OSA patients using routine clinical polysomnography alone. We use the concept that spontaneous ventilatory fluctuations due to apnoeas/hypopnoeas (disturbance) result in opposing changes in ventilatory drive (response) as determined by loop gain (response/disturbance). Fitting a simple ventilatory control model (including chemical and arousal contributions to ventilatory drive) to the ventilatory pattern of OSA reveals the underlying loop gain. Following mathematical-model validation, we critically tested our method in patients with OSA by comparison with a standard (continuous positive airway pressure (CPAP) drop method), and by assessing its ability to detect the known reduction in loop gain with oxygen and acetazolamide. Our method quantified loop gain from baseline polysomnography (correlation versus CPAP-estimated loop gain: n=28; r=0.63, p<0.001), detected the known reduction in loop gain with oxygen (n=11; mean±SEM change in loop gain (ΔLG) −0.23±0.08, p=0.02) and acetazolamide (n=11; ΔLG −0.20±0.06, p=0.005), and predicted the OSA response to loop gain-lowering therapy. We validated a means to quantify the ventilatory control contribution to OSA pathogenesis using clinical polysomnography, enabling identification of likely responders to therapies targeting ventilatory control. PMID:25323235

Controlled atmosphere stunning of broiler chickens. II. Effects on behaviour, physiology and meat quality in a commercial processing plant.

PubMed

McKeegan, D E F; Abeyesinghe, S M; McLeman, M A; Lowe, J C; Demmers, T G M; White, R P; Kranen, R W; van Bemmel, H; Lankhaar, J A C; Wathes, C M

2007-08-01

1. The effects of controlled atmosphere stunning on behavioural and physiological responses, and carcase and meat quality of broiler chickens were studied experimentally in a full scale processing plant. 2. The gas mixtures tested were a single phase hypercapnic anoxic mixture of 60% Ar and 30% CO(2) in air with <2% O(2), and a biphasic hypercapnic hyperoxygenation mixture, comprising an anaesthetic phase, 40% CO(2), 30% O(2), 30% N(2), followed by an euthanasia phase, 80% CO(2), 5% O(2), 15% N(2). 3. Birds stunned with Ar + CO(2) were more often observed to flap their wings earlier, jump, paddle their legs, twitch and lie dorsally (rather than ventrally) than those stunned with CO(2) + O(2). These behaviours indicate a more agitated response with more severe convulsions during hypercapnic anoxia, thereby introducing greater potential for injury. 4. Heart rate during the first 100 s of gas stunning was similar for both gases, after which it remained constant at approximately 230 beats/min for CO(2) + O(2) birds whereas it declined gently for Ar + CO(2) birds. 5. In terms of carcase and meat quality, there appeared to be clear advantages to the processor in using CO(2) + O(2) rather than Ar + CO(2) to stun broiler chickens, for example, a much smaller number of fractured wings (1.6 vs. 6.8%) with fewer haemorrhages of the fillet. 6. This study supports the conclusions of both laboratory and pilot scale experiments that controlled atmosphere stunning of broiler chickens based upon a biphasic hypercapnic hyperoxygenation approach has advantages, in terms of welfare and carcase and meat quality, over a single phase hypercapnic anoxic approach employing 60% Ar and 30% CO(2) in air with <2% O(2).

Effects of Hypercapnia and Hypercapnic Acidosis on Hospital Mortality in Mechanically Ventilated Patients.

PubMed

Tiruvoipati, Ravindranath; Pilcher, David; Buscher, Hergen; Botha, John; Bailey, Michael

2017-07-01

Lung-protective ventilation is used to prevent further lung injury in patients on invasive mechanical ventilation. However, lung-protective ventilation can cause hypercapnia and hypercapnic acidosis. There are no large clinical studies evaluating the effects of hypercapnia and hypercapnic acidosis in patients requiring mechanical ventilation. Multicenter, binational, retrospective study aimed to assess the impact of compensated hypercapnia and hypercapnic acidosis in patients receiving mechanical ventilation. Data were extracted from the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database over a 14-year period where 171 ICUs contributed deidentified data. Patients were classified into three groups based on a combination of pH and carbon dioxide levels (normocapnia and normal pH, compensated hypercapnia [normal pH with elevated carbon dioxide], and hypercapnic acidosis) during the first 24 hours of ICU stay. Logistic regression analysis was used to identify the independent association of hypercapnia and hypercapnic acidosis with hospital mortality. Nil. A total of 252,812 patients (normocapnia and normal pH, 110,104; compensated hypercapnia, 20,463; and hypercapnic acidosis, 122,245) were included in analysis. Patients with compensated hypercapnia and hypercapnic acidosis had higher Acute Physiology and Chronic Health Evaluation III scores (49.2 vs 53.2 vs 68.6; p < 0.01). The mortality was higher in hypercapnic acidosis patients when compared with other groups, with the lowest mortality in patients with normocapnia and normal pH. After adjusting for severity of illness, the adjusted odds ratio for hospital mortality was higher in hypercapnic acidosis patients (odds ratio, 1.74; 95% CI, 1.62-1.88) and compensated hypercapnia (odds ratio, 1.18; 95% CI, 1.10-1.26) when compared with patients with normocapnia and normal pH (p < 0.001). In patients with hypercapnic acidosis, the mortality increased with increasing PCO2 until 65 mm Hg after which the mortality plateaued. Hypercapnic acidosis during the first 24 hours of intensive care admission is more strongly associated with increased hospital mortality than compensated hypercapnia or normocapnia.

Effects and Mechanisms by Which Hypercapnic Acidosis Inhibits Sepsis-Induced Canonical Nuclear Factor-κB Signaling in the Lung.

PubMed

Masterson, Claire; O'Toole, Daniel; Leo, Annemarie; McHale, Patricia; Horie, Shahd; Devaney, James; Laffey, John G

2016-04-01

Diverse effects of hypercapnic acidosis are mediated via inhibition of nuclear factor-κB, a pivotal transcription factor, in the setting of injury, inflammation, and repair, but the underlying mechanisms of action of hypercapnic acidosis on this pathway is unclear. We aim to examine the effect of hypercapnic acidosis on the nuclear factor-κB pathway in the setting of Escherichia coli-induced lung injury and characterize the underlying mechanisms in subsequent in vitro studies. In vivo animal study and subsequent in vitro studies. University Research Laboratory. Adult male Sprague-Dawley rats and pulmonary epithelial cells. Following pulmonary IκBα-SuperRepressor transgene overexpression or sham and intratracheal E. coli inoculation, rats underwent 4 hours of mechanical ventilation under normocapnia or hypercapnic acidosis, and nuclear factor-κB activation, animal survival, lung injury, and cytokine profile were assessed. Subsequent in vitro studies examined the effect of hypercapnic acidosis on specific nuclear factor-κB canonical pathway kinases via overexpression of these components and in vitro kinase activity assays. The effect of hypercapnic acidosis on the p50/p65 nuclear factor-κB heterodimer was then assessed. Hypercapnic acidosis and IκBα-SuperRepressor transgene overexpression reduced E. coli-induced lung inflammation and injury, decreased nuclear factor-κB activity, and increased animal survival. Hypercapnic acidosis inhibited canonical nuclear factor-κB signaling via reduced phosphorylative activation, reducing IκB kinase-β activation and intrinsic activity, thereby decreasing IκBα degradation, and subsequent nuclear factor-κB translocation. Hypercapnic acidosis also directly reduced DNA binding of the nuclear factor-κB p65 subunit, although this effect was less marked. Hypercapnic acidosis reduced E. coli inflammation and lung injury in vivo and reduced nuclear factor-κB activation predominantly by inhibiting the activation and intrinsic activity of IκB kinase-β.

Low-dose morphine elicits ventilatory excitant and depressant responses in conscious rats: Role of peripheral μ-opioid receptors.

PubMed

Henderson, Fraser; May, Walter J; Gruber, Ryan B; Young, Alex P; Palmer, Lisa A; Gaston, Benjamin; Lewis, Stephen J

2013-08-01

The systemic administration of morphine affects ventilation via a mixture of central and peripheral actions. The aims of this study were to characterize the ventilatory responses elicited by a low dose of morphine in conscious rats; to determine whether tolerance develops to these responses; and to determine the potential roles of peripheral μ-opioid receptors (μ-ORs) in these responses. Ventilatory parameters were monitored via unrestrained whole-body plethysmography. Conscious male Sprague-Dawley rats received an intravenous injection of vehicle or the peripherally-restricted μ-OR antagonist, naloxone methiodide (NLXmi), and then three successive injections of morphine (1 mg/kg) given 30 min apart. The first injection of morphine in vehicle-treated rats elicited an array of ventilatory excitant (i.e., increases in frequency of breathing, minute volume, respiratory drive, peak inspiratory and expiratory flows, accompanied by decreases in inspiratory time and end inspiratory pause) and inhibitory (i.e., a decrease in tidal volume and an increase in expiratory time) responses. Subsequent injections of morphine elicited progressively and substantially smaller responses. The pattern of ventilatory responses elicited by the first injection of morphine was substantially affected by pretreatment with NLXmi whereas NLXmi minimally affected the development of tolerance to these responses. Low-dose morphine elicits an array of ventilatory excitant and depressant effects in conscious rats that are subject to the development of tolerance. Many of these initial actions of morphine appear to involve activation of peripheral μ-ORs whereas the development of tolerance to these responses does not.

Ventilatory responses to acute and chronic hypoxia are altered in female but not male Paskin-deficient mice.

PubMed

Soliz, Jorge; Soulage, Christophe; Borter, Emanuela; van Patot, Martha Tissot; Gassmann, Max

2008-08-01

Proteins harboring a Per-Arnt-Sim (PAS) domain are versatile and allow archaea, bacteria, and plants to sense oxygen partial pressure, as well as light intensity and redox potential. A PAS domain associated with a histidine kinase domain is found in FixL, the oxygen sensor molecule of Rhizobium species. PASKIN is the mammalian homolog of FixL, but its function is far from being understood. Using whole body plethysmography, we evaluated the ventilatory response to acute and chronic hypoxia of homozygous deficient male and female PASKIN mice (Paskin-/-). Although only slight ventilatory differences were found in males, female Paskin-/- mice increased ventilatory response to acute hypoxia. Unexpectedly, females had an impaired ability to reach ventilatory acclimatization in response to chronic hypoxia. Central control of ventilation occurs in the brain stem respiratory centers and is modulated by catecholamines via tyrosine hydroxylase (TH) activity. We observed that TH activity was altered in male and female Paskin-/- mice. Peripheral chemoreceptor effects on ventilation were evaluated by exposing animals to hyperoxia (Dejours test) and domperidone, a peripheral ventilatory stimulant drug directly affecting the carotid sinus nerve discharge. Male and female Paskin-/- had normal peripheral chemosensory (carotid bodies) responses. In summary, our observations suggest that PASKIN is involved in the central control of hypoxic ventilation, modulating ventilation in a gender-dependent manner.

Short-Term Modulation of the Ventilatory Response to Exercise is Preserved in Obstructive Sleep Apnea

PubMed Central

Bernhardt, Vipa; Mitchell, Gordon S.; Lee, Won Y.; Babb, Tony G.

2016-01-01

Background The ventilatory response to exercise can be transiently adjusted in response to environmentally (e.g., breathing apparatus) or physiologically altered conditions (e.g., respiratory disease), maintaining constant relative arterial PCO2 regulation from rest to exercise (Mitchell and Babb, 2006); this augmentation is called short-term modulation (STM) of the exercise ventilatory response. Obesity and/or obstructive sleep apnea could affect the exercise ventilatory response and the capacity for STM due to chronically increased mechanical and/or ventilatory loads on the respiratory system, and/or recurrent (chronic) intermittent hypoxia experienced during sleep. We hypothesized that: 1) the exercise ventilatory response is augmented in obese OSA patients compared with obese non-OSA adults, and 2) the capacity for STM with added dead space is diminished in obese OSA patients. Methods Nine obese adults with OSA (age: 39 ± 6 yr, BMI: 40 ± 5 kg/m2, AHI: 25 ± 24 events/hr [range 6–73], mean ± SD) and 8 obese adults without OSA (age: 38 ± 10 yr, BMI: 37 ± 6 kg/m2, AHI: 1 ± 2) completed three, 20-min bouts of constant-load submaximal cycling exercise (8 min rest, 6 min at 10 and 30 W) with or without added external dead space (200 or 400 ml; 20 min rest between bouts). Steady-state measurements were made of ventilation (V̇E), oxygen consumption (V̇O2), carbon dioxide production (V̇CO2), and end-tidal PCO2 (PETCO2). The exercise ventilatory response was defined as the slope of the V̇E-V̇CO2 relationship (ΔV̇E/ΔV̇CO2). Results In control (i.e. no added dead space), the exercise ventilatory response was not significantly different between non-OSA and OSA groups (ΔV̇E/ΔV̇CO2 slope: 30.5 ± 4.2 vs 30.5 ± 3.8, p > 0.05); PETCO2 regulation from rest to exercise did not differ between groups (p > 0.05). In trials with added external dead space, ΔV̇E/ΔV̇CO2 increased with increased dead space (p < 0.05) and the PETCO2 change from rest to exercise remained small (<2 mmHg) in both groups, demonstrating STM. There were no significant differences between groups. Conclusions Contrary to our hypotheses: 1) the exercise ventilatory response is not increased in obese OSA patients compared with obese non-OSA adults, and 2) the capacity for STM with added dead space is preserved in obese OSA and non-OSA adults. PMID:27840272

REAL-TIME MONITORING FOR TOXICITY CAUSED BY HARMFUL ALGAL BLOOMS AND OTHER WATER QUALITY PERTURBATIONS

EPA Science Inventory

This project, sponsored by EPA's Environmental Monitoring for Public Access and Community Tracking (EMPACT) program, evaluated the ability of an automated biological monitoring system that measures fish ventilatory responses (ventilatory rate, ventilatory depth, and cough rate) t...

The ventilatory responsiveness to CO2 below eupnoea as a determinant of ventilatory stability in sleep

PubMed Central

Dempsey, Jerome A; Smith, Curtis A; Przybylowski, Tadeuez; Chenuel, Bruno; Xie, Ailiang; Nakayama, Hideaki; Skatrud, James B

2004-01-01

Sleep unmasks a highly sensitive hypocapnia-induced apnoeic threshold, whereby apnoea is initiated by small transient reductions in arterial CO2 pressure (PaCO2) below eupnoea and respiratory rhythm is not restored until PaCO2 has risen significantly above eupnoeic levels. We propose that the ‘CO2 reserve’ (i.e. the difference in PaCO2 between eupnoea and the apnoeic threshold (AT)), when combined with ‘plant gain’ (or the ventilatory increase required for a given reduction in PaCO2) and ‘controller gain’ (ventilatory responsiveness to CO2 above eupnoea) are the key determinants of breathing instability in sleep. The CO2 reserve varies inversely with both plant gain and the slope of the ventilatory response to reduced CO2 below eupnoea; it is highly labile in non-random eye movement (NREM) sleep. With many types of increases or decreases in background ventilatory drive and PaCO2, the slope of the ventilatory response to reduced PaCO2 below eupnoea remains unchanged from control. Thus, the CO2 reserve varies inversely with plant gain, i.e. it is widened with hyperventilation and narrowed with hypoventilation, regardless of the stimulus and whether it acts primarily at the peripheral or central chemoreceptors. However, there are notable exceptions, such as hypoxia, heart failure, or increased pulmonary vascular pressures, which all increase the slope of the CO2 response below eupnoea and narrow the CO2 reserve despite an accompanying hyperventilation and reduced plant gain. Finally, we review growing evidence that chemoreceptor-induced instability in respiratory motor output during sleep contributes significantly to the major clinical problem of cyclical obstructive sleep apnoea. PMID:15284345

Ventilatory responses to hypercapnia and hypoxia after 6 h passive hyperventilation in humans

PubMed Central

Ren, Xiaohui; Robbins, Peter A

1999-01-01

Acute exposure to hypoxia stimulates ventilation and induces hypocapnia. Long-term exposure to hypoxia generates changes in respiratory control known as ventilatory acclimatization to hypoxia. The object of this study was to investigate the degree to which the hyperventilation and hypocapnia can induce the changes known as ventilatory acclimatization to hypoxia, in the absence of the primary hypoxic stimulus itself.Three 6 h protocols were each performed on twelve healthy volunteers: (1) passive hypocapnic hyperventilation, with end-tidal CO2 pressure (PET,CO2) held 10 Torr below the eupnoeic value; (2) passive eucapnic hyperventilation, with PET,CO2 maintained eucapnic; (3) control.Ventilatory responses to acute hypercapnia and hypoxia were assessed before and half an hour after each protocol.The presence of prior hypocapnia, but not prior hyperventilation, caused a reduction in air-breathing PET,CO2 (P < 0·05, ANOVA), and a leftwards shift of the ventilatory response to hypercapnia (P < 0·05). The presence of prior hyperventilation, but not prior hypocapnia, caused an increase in the ventilatory sensitivity to CO2 (P < 0·05). No significant effects of any protocol were detected on the ventilatory sensitivity to hypoxia.We conclude that following 6 h of passive hyperventilation: (i) the left shift of the VE-PET,CO2 relationship is due to alkalosis and not to hyperventilation; (ii) the increase in slope of the VE-PET,CO2 relationship is due to the hyperventilation and not the alkalosis; and (iii) ventilatory sensitivity to hypoxia is unaltered. PMID:9882758

Ventilatory response to hypercarbia in newborns of smoking and substance-misusing mothers.

PubMed

Ali, Kamal; Wolff, Kim; Peacock, Janet L; Hannam, Simon; Rafferty, Gerrard F; Bhat, Ravindra; Greenough, Anne

2014-07-01

Infants of mothers who smoked (S) or substance misused (SM) during pregnancy have an increased risk of sudden infant death syndrome (SIDS). To test the hypothesis that infants of S and SM mothers compared with infants of non-substance-misusing, nonsmoking mothers (control subjects) would have a reduced ventilatory response to hypercarbia and that any reduction would be greater in the SM infants. Infants were assessed before maternity/neonatal unit discharge. Maternal and infant urine samples were obtained and tested for cotinine, cannabinoids, opiates, amphetamines, methadone, cocaine, and benzodiazepines. Respiratory flow and Vt were measured using a pneumotachograph inserted into a face mask placed over the infant's mouth and nose. The ventilatory responses to three levels of inspired carbon dioxide (0 [baseline], 2, and 4% CO2) were assessed. Twenty-three SM, 34 S, and 22 control infants were assessed. The birth weight of the control subjects was higher than the SM and S infants (P = 0.017). At baseline, SM infants had a higher respiratory rate (P = 0.003) and minute volume (P = 0.007) compared with control subjects and S infants. Both the SM and S infants had a lower ventilatory response to 2% (P < 0.001) and 4% (P < 0.001) CO2 than the control subjects. The ventilatory response to CO2 was lower in the SM infants compared with the S infants (P = 0.009). These results are consistent with infants of smoking mothers and substance misuse/smoking mothers having a dampened ventilatory response to hypercarbia, which is particularly marked in the latter group.

Successful management of drug-induced hypercapnic acidosis with naloxone and noninvasive positive pressure ventilation.

PubMed

Agrafiotis, Michalis; Tryfon, Stavros; Siopi, Demetra; Chassapidou, Georgia; Galanou, Artemis; Tsara, Venetia

2015-02-01

A 74-year-old man was referred to our hospital due to deteriorating level of consciousness and desaturation. His Glasgow Coma Scale was 6, and his pupils were constricted but responded to light. Chest radiograph was negative for significant findings. Arterial blood gas evaluation on supplemental oxygen revealed severe acute on chronic respiratory acidosis: pH 7.15; PCO2, 133 mm Hg; PO2,64 mm Hg; and HCO3, 31 mmol/L. He regained full consciousness (Glasgow Coma Scale, 15) after receiving a 0.4 mg dose of naloxone, but because of persistent severe respiratory acidosis (pH 7.21; PCO2, 105 mm Hg), he was immediately commenced on noninvasive positive pressure ventilation (NIV) displaying a remarkable improvement in arterial blood gas values within the next few hours. However, in the days that followed, he remained dependent on NIV, and he was finally discharged on a home mechanical ventilation prescription. In cases of drug-induced respiratory depression, NIV should be regarded as an acceptable treatment, as it can provide ventilatory support without the increased risks associated with invasive mechanical ventilation.

Cold stimulates the behavioral response to hypoxia in newborn mice.

PubMed

Bollen, Bieke; Bouslama, Myriam; Matrot, Boris; Rotrou, Yann; Vardon, Guy; Lofaso, Frédéric; Van den Bergh, Omer; D'Hooge, Rudi; Gallego, Jorge

2009-05-01

In newborns, hypoxia elicits increased ventilation, arousal followed by defensive movements, and cries. Cold is known to affect the ventilatory response to hypoxia, but whether it affects the arousal response remains unknown. The aim of the present study was to assess the effects of cold on the ventilatory and arousal responses to hypoxia in newborn mice. We designed an original platform measuring noninvasively and simultaneously the breathing pattern by whole body plethysmography, body temperature by infrared thermography, as well as motor and ultrasonic vocal (USV) responses. Six-day-old mice were exposed twice to 10% O(2) for 3 min at either cold temperature (26 degrees C) or thermoneutrality (33 degrees C). At 33 degrees C, hypoxia elicited a marked increase in ventilation followed by a small ventilatory decline, small motor response, and almost no USVs. Body temperature was not influenced by hypoxia, and oxygen consumption (Vo(2)) displayed minimal changes. At 26 degrees C, hypoxia elicited a slight increase in ventilation with a large ventilatory decline and a large drop of Vo(2). This response was accompanied by marked USV and motor responses. Hypoxia elicited a small decrease in temperature after the return to normoxia, thus precluding any causal influence on the motor and USV responses to hypoxia. In conclusion, cold stimulated arousal and stress responses to hypoxia, while depressing hypoxic hyperpnea. Arousal is an important defense mechanism against sleep-disordered breathing. The dissociation between ventilatory and behavioral responses to hypoxia suggests that deficits in the arousal response associated with sleep breathing disorders cannot be attributed to a depressed hypoxic response.

Effect of exercise training on ventilatory efficiency in patients with heart disease: a review.

PubMed

Prado, D M L; Rocco, E A; Silva, A G; Rocco, D F; Pacheco, M T; Furlan, V

2016-06-20

The analysis of ventilatory efficiency in cardiopulmonary exercise testing has proven useful for assessing the presence and severity of cardiorespiratory diseases. During exercise, efficient pulmonary gas exchange is characterized by uniform matching of lung ventilation with perfusion. By contrast, mismatching is marked by inefficient pulmonary gas exchange, requiring increased ventilation for a given CO2 production. The etiology of increased and inefficient ventilatory response to exercise in heart disease is multifactorial, involving both peripheral and central mechanisms. Exercise training has been recommended as non-pharmacological treatment for patients with different chronic cardiopulmonary diseases. In this respect, previous studies have reported improvements in ventilatory efficiency after aerobic exercise training in patients with heart disease. Against this background, the primary objective of the present review was to discuss the pathophysiological mechanisms involved in abnormal ventilatory response to exercise, with an emphasis on both patients with heart failure syndrome and coronary artery disease. Secondly, special focus was dedicated to the role of aerobic exercise training in improving indices of ventilatory efficiency among these patients, as well as to the underlying mechanisms involved.

Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo.

PubMed

Palpant, Nathan J; D'Alecy, Louis G; Metzger, Joseph M

2009-05-01

Intracellular acidosis is a profound negative regulator of myocardial performance. We hypothesized that titrating myofilament calcium sensitivity by a single histidine substituted cardiac troponin I (A164H) would protect the whole animal physiological response to acidosis in vivo. To experimentally induce severe hypercapnic acidosis, mice were exposed to a 40% CO(2) challenge. By echocardiography, it was found that systolic function and ventricular geometry were maintained in cTnI A164H transgenic (Tg) mice. By contrast, non-Tg (Ntg) littermates experienced rapid and marked cardiac decompensation during this same challenge. For detailed hemodymanic assessment, Millar pressure-conductance catheterization was performed while animals were treated with a beta-blocker, esmolol, during a severe hypercapnic acidosis challenge. Survival and load-independent measures of contractility were significantly greater in Tg vs. Ntg mice. This assay showed that Ntg mice had 100% mortality within 5 min of acidosis. By contrast, systolic and diastolic function were protected in Tg mice during acidosis, and they had 100% survival. This study shows that, independent of any beta-adrenergic compensation, myofilament-based molecular manipulation of inotropy by histidine-modified troponin I maintains cardiac inotropic and lusitropic performance and markedly improves survival during severe acidosis in vivo.

Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex.

PubMed

Hennessy, Morgan L; Corcoran, Andrea E; Brust, Rachael D; Chang, YoonJeung; Nattie, Eugene E; Dymecki, Susan M

2017-02-15

Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 ( Tac1 ) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1 , referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine -N- oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO 2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO 2 Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using genetic tools, we characterize a 5-HT neuron subtype defined by expression of Tachykinin1 and Pet1 ( Tac1-Pet1 neurons), mapping soma localization to the caudal medulla primarily and axonal projections to brainstem motor nuclei most prominently, and, when silenced, observed blunting of the ventilatory response to inhaled CO 2 Tac1-Pet1 neurons thus appear distinct from and contrast previously described Egr2-Pet1 neurons, which project primarily to chemosensory integration centers and are themselves chemosensitive. Copyright © 2017 the authors 0270-6474/17/371807-13$15.00/0.

Early life sensory ability-ventilatory responses of thornback ray embryos (Raja clavata) to predator-type electric fields.

PubMed

Ball, Rachel Emma; Oliver, Matthew Kenneth; Gill, Andrew Bruce

2016-07-01

Predator avoidance is fundamental for survival and it can be particularly challenging for prey animals if physical movement away from a predatory threat is restricted. Many sharks and rays begin life within an egg capsule that is attached to the sea bed. The vulnerability of this sedentary life stage is exacerbated in skates (Rajidae) as the compulsory ventilatory activity of embryos makes them conspicuous to potential predators. Embryos can reduce this risk by mediating ventilatory activity if they detect the presence of a predator using an acute electrosense. To determine how early in embryonic life predator elicited behavioral responses can occur, the reactions of three different age groups (1/3 developed, 2/3 developed, and near hatching) of embryonic thornback rays Raja clavata were tested using predator-type electric field stimuli. Egg capsules were exposed to continuous or intermittent stimuli in order to assess varying predator-type encounter scenarios on the ventilatory behavior of different developmental stages. All embryos reacted with a "freeze response" following initial electric field (E-field) exposure, ceasing ventilatory behavior in response to predator presence, demonstrating electroreceptive functionality for the first time at the earliest possible stage in ontogeny. This ability coincided with the onset of egg ventilatory behavior and may represent an effective means to enhance survival. A continuous application of stimuli over time revealed that embryos can adapt their behavior and resume normal activity, whereas when presented intermittently, the E-field resulted in a significant reduction in overall ventilatory activity across all ages. Recovery from stimuli was significantly quicker in older embryos, potentially indicative of the trade-off between avoiding predation and adequate respiration. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 721-729, 2016. © 2015 Wiley Periodicals, Inc.

Update: Non-Invasive Positive Pressure Ventilation in Chronic Respiratory Failure Due to COPD.

PubMed

Altintas, Nejat

2016-01-01

Long-term non-invasive positive pressure ventilation (NPPV) has widely been accepted to treat chronic hypercapnic respiratory failure arising from different etiologies. Although the survival benefits provided by long-term NPPV in individuals with restrictive thoracic disorders or stable, slowly-progressing neuromuscular disorders are overwhelming, the benefits provided by long-term NPPV in patients with chronic obstructive pulmonary disease (COPD) remain under question, due to a lack of convincing evidence in the literature. In addition, long-term NPPV reportedly failed in the classic trials to improve important physiological parameters such as arterial blood gases, which might serve as an explanation as to why long-term NPPV has not been shown to substantially impact on survival. However, high intensity NPPV (HI-NPPV) using controlled NPPV with the highest possible inspiratory pressures tolerated by the patient has recently been described as a new and promising approach that is well-tolerated and is also capable of improving important physiological parameters such as arterial blood gases and lung function. This clearly contrasts with the conventional approach of low-intensity NPPV (LI-NPPV) that uses considerably lower inspiratory pressures with assisted forms of NPPV. Importantly, HI-NPPV was very recently shown to be superior to LI-NPPV in terms of improved overnight blood gases, and was also better tolerated than LI-NPPV. Furthermore, HI-NPPV, but not LI-NPPV, improved dyspnea, lung function and disease-specific aspects of health-related quality of life. A recent study showed that long-term treatment with NPPV with increased ventilatory pressures that reduced hypercapnia was associated with significant and sustained improvements in overall mortality. Thus, long-term NPPV seems to offer important benefits in this patient group, but the treatment success might be dependent on effective ventilatory strategies.

Determinants of ventilation and pulmonary artery pressure during early acclimatization to hypoxia in humans

PubMed Central

Fatemian, Marzieh; Herigstad, Mari; Croft, Quentin P. P.; Formenti, Federico; Cardenas, Rosa; Wheeler, Carly; Smith, Thomas G.; Friedmannova, Maria; Dorrington, Keith L.

2015-01-01

Key points Lung ventilation and pulmonary artery pressure rise progressively in response to 8 h of hypoxia, changes described as ‘acclimatization to hypoxia’. Acclimatization responses differ markedly between humans for unknown reasons.We explored whether the magnitudes of the ventilatory and vascular responses were related, and whether the degree of acclimatization could be predicted by acute measurements of ventilatory and vascular sensitivities.In 80 healthy human volunteers measurements of acclimatization were made before, during, and after a sustained exposure to 8 h of isocapnic hypoxia.No correlation was found between measures of ventilatory and pulmonary vascular acclimatization.The ventilatory chemoreflex sensitivities to acute hypoxia and hypercapnia all increased in proportion to their pre‐acclimatization values following 8 h of hypoxia. The peripheral (rapid) chemoreflex sensitivity to CO2, measured before sustained hypoxia against a background of hyperoxia, was a modest predictor of ventilatory acclimatization to hypoxia. This finding has relevance to predicting human acclimatization to the hypoxia of altitude. Abstract Pulmonary ventilation and pulmonary arterial pressure both rise progressively during the first few hours of human acclimatization to hypoxia. These responses are highly variable between individuals, but the origin of this variability is unknown. Here, we sought to determine whether the variabilities between different measures of response to sustained hypoxia were related, which would suggest a common source of variability. Eighty volunteers individually underwent an 8‐h isocapnic exposure to hypoxia (end‐tidal P O2=55 Torr) in a purpose‐built chamber. Measurements of ventilation and pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography were made during the exposure. Before and after the exposure, measurements were made of the ventilatory sensitivities to acute isocapnic hypoxia (GpO2) and hyperoxic hypercapnia, the latter divided into peripheral (G pC O2) and central (G cC O2) components. Substantial acclimatization was observed in both ventilation and PASP, the latter being 40% greater in women than men. No correlation was found between the magnitudes of pulmonary ventilatory and pulmonary vascular responses. For GpO2, G pC O2 and G cC O2, but not the sensitivity of PASP to acute hypoxia, the magnitude of the increase during acclimatization was proportional to the pre‐acclimatization value. Additionally, the change in GpO2 during acclimatization to hypoxia correlated well with most other measures of ventilatory acclimatization. Of the initial measurements prior to sustained hypoxia, only G pC O2 predicted the subsequent rise in ventilation and change in GpO2 during acclimatization. We conclude that the magnitudes of the ventilatory and pulmonary vascular responses to sustained hypoxia are predominantly determined by different factors and that the initial G pC O2 is a modest predictor of ventilatory acclimatization. PMID:25907672

Effect of menstrual cycle phase on the ventilatory response to rising body temperature during exercise.

PubMed

Hayashi, Keiji; Kawashima, Takayo; Suzuki, Yuichi

2012-07-01

To examine the effect of menstrual cycle on the ventilatory sensitivity to rising body temperature, ten healthy women exercised for ~60 min on a cycle ergometer at 50% of peak oxygen uptake during the follicular and luteal phases of their cycle. Esophageal temperature, mean skin temperature, mean body temperature, minute ventilation, and tidal volume were all significantly higher at baseline and during exercise in the luteal phase than the follicular phase. On the other hand, end-tidal partial pressure of carbon dioxide was significantly lower during exercise in the luteal phase than the follicular phase. Plotting ventilatory parameters against esophageal temperature revealed there to be no significant menstrual cycle-related differences in the slopes or intercepts of the regression lines, although minute ventilation and tidal volume did significantly differ during exercise with mild hyperthermia. To evaluate the cutaneous vasodilatory response, relative laser-Doppler flowmetry values were plotted against mean body temperature, which revealed that the mean body temperature threshold for cutaneous vasodilation was significantly higher in the luteal phase than the follicular phase, but there were no significant differences in the sensitivity or peak values. These results suggest that the menstrual cycle phase influences the cutaneous vasodilatory response during exercise and the ventilatory response at rest and during exercise with mild hyperthermia, but it does not influence ventilatory responses during exercise with moderate hyperthermia.

Metabolic and ventilatory responses to submaximal and maximal exercise using different breathing assemblies.

PubMed

Evans, B W; Potteiger, J A

1995-06-01

This study compared ventilatory and metabolic responses during exercise using three breathing assemblies: mouthpiece/noseclip (BV); mouth/face mask (MM); and facemask (FM). Ten male runners completed three maximal treadmill tests with breathing assembly randomly assigned. Metabolic and ventilatory data were recorded every 15s, and heart rate (HR) and rating of perceived exertion (RPE) each min. No significant differences were found for treadmill run time, HRmax, respiratory exchange ratio (RER), and RPE, indicating similar efforts on all trials. No significant differences were found at maximal exercise for VO2 minute ventilation (VE), tidal volume (VT), and breathing frequency (f). At ventilatory threshold (TVENT), VO2, VE, and f were not significantly different. However, peak flow (PF) was significantly higher for BV than FM, and VT was significantly higher for BV than MM and FM. Results indicate alterations in ventilatory mechanics occur at TVENT, but type of breathing assembly does not significantly affect maximal values.

End-Tidal CO2 Tension Is Predictive of Effective Nocturnal Oxygen Therapy in Patients with Chronic Heart Failure and Central Sleep Apnea.

PubMed

Sugimura, Koichiro; Shinozaki, Tsuyoshi; Fukui, Shigefumi; Ogawa, Hiromasa; Shimokawa, Hiroaki

2016-05-01

Central sleep apnea (CSA) is characterized by recurring cycles of crescendo-decrescendo ventilation during sleep, and enhances sympathetic nerve activity. Thus CSA has a prognostic impact in patients with chronic heart failure (CHF). Although nocturnal oxygen (O2) therapy decreases frequency of CSA and improves functional exercise capacity, it is also known that some non-responders to the therapy exist. We thus aimed to identify predictors of responders to nocturnal O2 therapy in CHF patients with CSA. In 12 CHF patients with CSA hospitalized at our department, sleep study was performed at 2 consecutive nights. Patients nasally inhaled O2 at either the first or second night in a randomized manner. To predict the percentage reduction in apnea-hypopnea index (%ΔAHI) in response to the nocturnal O2 therapy, we performed multiple regression analysis with a stepwise method with variables including age, brain-natriuretic peptide, circulation time, baseline AHI, hypercapnic ventilatory response and end-tidal carbon dioxide tension (PETCO2). Nocturnal O2 therapy significantly decreased AHI (from 32 ± 13 /h to 12 ± 10 /h, P < 0.0001). Among the possible predictors, PETCO2 was the only variable that is predictive of % changes in AHI. Receiver operating characteristics analysis determined 4.25% as the optimal cutoff PETCO2 level to identify responder to nocturnal O2 therapy (> 50% reduction of AHI), with 88.9% of sensitivity and 66.7% of specificity. In conclusion, PETCO2 is useful to predict the efficacy of O2 therapy in CHF patients with CSA, providing important information to the current nocturnal O2 therapy.

Medullary 5-HT neurons: Switch from tonic respiratory drive to chemoreception during postnatal development

PubMed Central

Cerpa, Veronica J.; Wu, Yuanming; Bravo, Eduardo; Teran, Frida A.; Flynn, Rachel S.; Richerson, George B.

2016-01-01

Serotonin (5-HT) neurons contribute to respiratory chemoreception in adult mice, but it is unclear whether they play a similar role in neonatal mice. We studied breathing during development in Lmx1bf/f/p mice, which lack 5-HT neurons. From postnatal days 1–7 (P1–P7), ventilation of Lmx1bf/f/p mice breathing room air was 50% of WT mice (p < 0.001). By P12, baseline ventilation increased to a level equal to WT mice. In contrast, the hypercapnic ventilatory response (HCVR) of neonatal Lmx1bf/f/p and WT mice were equal to each other, but were both much less than adult WT mice. By P21 the HCVR of WT mice increased to near adult levels, but the HCVR of Lmx1bf/f/p mice had not changed, and was 42% less than WT mice. Primary cell cultures were prepared from the ventromedial medulla of neonatal mice, and patch-clamp recordings were made from neurons identified as serotonergic by expression of a reporter gene. In parallel with developmental changes of the HCVR in vivo, 5-HT neurons had little chemosensitivity to acidosis until 12 days in vitro (DIV), after which their response increased to reach a plateau around 25 DIV. Neonatal Lmx1bf/f/p mice displayed high mortality and decreased growth rate, and this worsened in hypoxia. Mortality was decreased in hyperoxia. These results indicate that maturation of 5-HT neurons contributes to development of respiratory CO2/pH chemoreception during the first few weeks of life in mice in vivo. A defect in the 5-HT system in early postnatal life decreases survival due in part to hypoxia. PMID:27619736

Ventilatory Responsiveness of Goats with Ablated Carotid Bodies,

DTIC Science & Technology

1982-06-03

R.A.Gabel, D.E. Leith, and V. Fencl 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT. TASK AREA & WORK UNIT NUMBERS US Army... vestigial ventilatory response to cyanide. These findings persisted throughout 10 the 5 months of our observation, in contrast with the observations of

Ventilatory acclimatization to hypoxia in mice: Methodological considerations.

PubMed

Ivy, Catherine M; Scott, Graham R

2017-01-01

We examined ventilatory acclimatization to hypoxia (VAH) in CD1 mice, and contrasted results obtained using the barometric method on unrestrained mice with pneumotachography and pulse oximetry on restrained mice. Responses to progressive step reductions in O 2 fraction (21%-8%) were assessed in mice acclimated to normoxia and hypobaric hypoxia (barometric pressure of 60kPa for 6-8 weeks). Hypoxia acclimation increased the hypoxic ventilatory response (primarily by increasing breathing frequency rather than tidal volume), arterial O 2 saturation (Sa O2 ) and heart rate in deep hypoxia, hypoxic chemosensitivity (ventilatory O 2 /CO 2 equivalents versus Sa O2 ), and respiratory water loss, and it blunted the hypoxic depression of metabolism and body temperature. Although some effects of hypoxia acclimation were qualitatively similar between methods, the effects were often greater in magnitude when assessed using pneumotachography. Furthermore, whereas hypoxia acclimation reduced ventilatory O 2 equivalent and increased pulmonary O 2 extraction in barometric experiments, it had the opposite effects in pneumotachography experiments. Our findings highlight the importance of considering the impact of how breathing is measured on the apparent responses to hypoxia. Copyright © 2016 Elsevier B.V. All rights reserved.

Control of ventilation during intravenous CO2 loading in the awake dog.

PubMed

Stremel, R W; Huntsman, D J; Casaburi, R; Whipp, B J; Wasserman, K

1978-02-01

The ventilatory response to venous CO2 loading and its effect on arterial CO2 tension was determined in five awake dogs. Blood, 200-500 ml/min, was diverted from a catheter in the right common carotid artery through a membrane gas exchanger and returned to the right jugular vein. CO2 loading was accomplished by changing the gas ventilating the gas exchanger from a mixture of 5% CO2 in air to 100% CO2. The ventilatory responses to this procedure were compared with those resulting from increased inspired CO2 concentrations (during which ventilation of the gas exchanger with the air and 5% CO2 mixture continued). The ventilatory response to each form of CO2 loading was computed as deltaVE/deltaPaco9. The mean ventilatory response to airway CO2 loading was 1.61 1/min per Torr PaCO2. The mean response for the venous CO2 loading was significantly higher and not significantly different from "infinite" CO2 sensitivity (i.e., isocapnic response). The results provide further evidence for a CO2-linked hyperpnea, not mediated by significant changes in mean arterial PCO2.

Severe spontaneous bradycardia associated with respiratory disruptions in rat pups with fewer brain stem 5-HT neurons

PubMed Central

Cummings, Kevin J.; Commons, Kathryn G.; Fan, Kenneth C.; Li, Aihua; Nattie, Eugene E.

2009-01-01

The medullary 5-HT system has potent effects on heart rate and breathing in adults. We asked whether this system mitigates the respiratory instability and bradycardias frequently occurring during the neonatal period. 5,7-Dihydroxytryptamine (5,7-DHT) or vehicle was administered to rat pups at postnatal day 2 (P2), and we then compared the magnitude of bradycardias occurring with disruptions to eupnea in treated and vehicle control littermates at P5–6 and P10–12. We then used a novel method that would allow accurate assessment of the ventilatory and heart rate responses to near square-wave challenges of hypoxia (10% O2), hypercapnia (5 and 8% CO2 in normoxia and hyperoxia), and asphyxia (8% CO2-10% O2), and to the induction of the Hering-Breuer inflation reflex (HBR), a potent, apnea-inducing reflex in newborns. The number of 5-HT-positive neurons was reduced ∼80% by drug treatment. At both ages, lesioned animals had considerably larger bradycardias during brief apnea; at P5–6, average and severe events were ∼50% and 70% greater, respectively, in lesioned animals (P = 0.002), whereas at P10–12, events were ∼ 23% and 50% greater (P = 0.018). However, lesioning had no effect on the HR responses to sudden gas challenge or the HBR. At P5–6, lesioned animals had reduced breathing frequency and ventilation (V̇e), but normal V̇e relative to metabolic rate (V̇e/V̇o2). At P10–12, lesioned animals had a more unstable breathing pattern (P = 0.04) and an enhanced V̇e response to moderate hypercapnia (P = 0.007). Within the first two postnatal weeks, the medullary 5-HT system plays an important role in cardiorespiratory control, mitigating spontaneous bradycardia, stabilizing the breathing pattern, and dampening the hypercapnic V̇e response. PMID:19369586

Brain stem NO modulates ventilatory acclimatization to hypoxia in mice.

PubMed

El Hasnaoui-Saadani, R; Alayza, R Cardenas; Launay, T; Pichon, A; Quidu, P; Beaudry, M; Léon-Velarde, F; Richalet, J P; Duvallet, A; Favret, F

2007-11-01

The objective of our study was to assess the role of neuronal nitric oxide synthase (nNOS) in the ventilatory acclimatization to hypoxia. We measured the ventilation in acclimatized Bl6/CBA mice breathing 21% and 8% oxygen, used a nNOS inhibitor, and assessed the expression of N-methyl-d-aspartate (NMDA) glutamate receptor and nNOS (mRNA and protein). Two groups of Bl6/CBA mice (n = 60) were exposed during 2 wk either to hypoxia [barometric pressure (PB) = 420 mmHg] or normoxia (PB = 760 mmHg). At the end of exposure the medulla was removed to measure the concentration of nitric oxide (NO) metabolites, the expression of NMDA-NR1 receptor, and nNOS by real-time RT-PCR and Western blot. We also measured the ventilatory response [fraction of inspired O(2) (Fi(O(2))) = 0.21 and 0.08] before and after S-methyl-l-thiocitrulline treatment (SMTC, nNOS inhibitor, 10 mg/kg ip). Chronic hypoxia caused an increase in ventilation that was reduced after SMTC treatment mainly through a decrease in tidal volume (Vt) in normoxia and in acute hypoxia. However, the difference observed in the magnitude of acute hypoxic ventilatory response [minute ventilation (Ve) 8% - Ve 21%] in acclimatized mice was not different. Acclimatization to hypoxia induced a rise in NMDA receptor as well as in nNOS and NO production. In conclusion, our study provides evidence that activation of nNOS is involved in the ventilatory acclimatization to hypoxia in mice but not in the hypoxic ventilatory response (HVR) while the increased expression of NMDA receptor expression in the medulla of chronically hypoxic mice plays a role in acute HVR. These results are therefore consistent with central nervous system plasticity, partially involved in ventilatory acclimatization to hypoxia through nNOS.

Response surface modeling of alfentanil-sevoflurane interaction on cardiorespiratory control and bispectral index.

PubMed

Dahan, A; Nieuwenhuijs, D; Olofsen, E; Sarton, E; Romberg, R; Teppema, L

2001-06-01

Respiratory depression is a serious side effect of anesthetics and opioids. The authors examined the influence of the combined administration of sevoflurane and alfentanil on ventilatory control, heart rate (HR), and Bispectral Index (BIS) in healthy volunteers. Step decreases in end-tidal partial pressure of oxygen from normoxia into hypoxia (approximately 50 mmHg) at constant end-tidal partial pressure of carbon dioxide (approximately 48 mmHg) were performed in nine male volunteers at various concentrations of alfentanil and sevoflurane, ranging from 0 to 50 ng/ml for alfentanil and from 0 to 0.4 end-tidal concentration (ET%) for sevoflurane, and with various combinations of alfentanil and sevoflurane. The alfentanil-sevoflurane interactions on normoxic resting (hypercapnic) ventilation (Vi), HR, hypoxic Vi, and HR responses and BIS were assessed by construction of response surfaces that related alfentanil and sevoflurane to effect using a population analysis. Concentration-effect relations were linear for alfentanil and sevoflurane. Synergistic interactions were observed for resting Vi and resting HR. Depression of Vi by 25% occurred at 38 +/- 11 ng/ml alfentanil (population mean +/- SE) and at 0.7 +/- 0.4 ET% sevoflurane. One possibility for 25% reduction when alfentanil and sevoflurane are combined is 13.4 ng/ml alfentanil plus 0.12 ET% sevoflurane. Additive interactions were observed for hypoxic Vi and HR responses and BIS. Depression of the hypoxic Vi response by 25% occurred at 16 +/- 1 ng/ml alfentanil and 0.14 +/- 0.05 ET% sevoflurane. The effect of sevoflurane on the BIS (25% reduction of BIS occurred at 0.45 +/- 0.08 ET%) was independent of the alfentanil concentration. Response surface modeling was used successfully to analyze the effect of interactions between two drugs on respiration. The combination of alfentanil and sevoflurane causes more depression of Vi and HR than does the summed effect of each drug administered separately. The effects of combining alfentanil and sevoflurane on hypoxic Vi and HR responses and BIS could be predicted from the separate dose-response curves. Over the dose range tested, the hypoxic response is more sensitive to the effects of anesthetics and opioids relative to resting ventilation.

Anoxia and Acidosis Tolerance of the Heart in an Air-Breathing Fish (Pangasianodon hypophthalmus).

PubMed

Joyce, William; Gesser, Hans; Bayley, Mark; Wang, Tobias

2015-01-01

Air breathing has evolved repeatedly in fishes and may protect the heart during stress. We investigated myocardial performance in the air-breathing catfish Pangasianodon hypophthalmus, a species that can withstand prolonged exposure to severe hypoxia and acidosis. Isometric ventricular preparations were exposed to anoxia, lactic acidosis, hypercapnic acidosis, and combinations of these treatments. Ventricular preparations were remarkably tolerant to anoxia, exhibiting an inotropic reduction of only 40%, which fully recovered during reoxygenation. Myocardial anoxia tolerance was unaffected by physiologically relevant elevations of bicarbonate concentration, in contrast to previous results in other fishes. Both lactic acidosis (5 mM; pH 7.10) and hypercapnic acidosis (10% CO2; pH 6.70) elicited a biphasic response, with an initial and transient decrease in force followed by overcompensation above control values. Spongy myocardial preparations were significantly more tolerant to hypercapnic acidosis than compact myocardial preparations. While ventricular preparations were tolerant to the isolated effects of anoxia and acidosis, their combination severely impaired myocardial performance and contraction kinetics. This suggests that air breathing may be a particularly important myocardial oxygen source during combined anoxia and acidosis, which may occur during exercise or environmental stress.

Changes in Ventilatory Response to Exercise in Trained Athletes: Respiratory Physiological Benefits Beyond Cardiovascular Performance.

PubMed

di Paco, Adriano; Dubé, Bruno-Pierre; Laveneziana, Pierantonio

2017-05-01

The beneficial impact of an 8-month competitive season on the ventilatory profile response to exercise in soccer players has never been evaluated. Ventilatory profile (evaluated by determining individual tidal volume [V T ] relative to minute ventilation [V E ] inflection points during exercise) and metabolic responses to incremental exercise were evaluated in 2 professional soccer teams before and after an 8-month competitive season. No differences between teams in anthropometric characteristics or in resting cardiopulmonary variables, included oxygen uptake (VO 2 ) and heart rate (HR), before and during the competitive season were found. At iso-speed, there were overall improvements in carbon dioxide output (VCO 2 ), V E /VO 2 , V E /VCO 2 , V E and respiratory frequency (fR) during the season. The V T /V E inflection points 1 and 2 occurred with greater exercise time, HR, VO 2 , VCO 2 , V E and V T during the competitive season. Despite very high baseline performance and a negligible improvement in VO 2 , an 8-month competitive season improved ventilatory profile response to exercise in elite athletes. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Development of a Female Atlas of Strengths

DTIC Science & Technology

1982-02-01

the maximum in water at 2%. The post- exercise hyperaemic response was greater for a given duration of contraction in water at 34 and 42% than at lower...references. 226 STUDY: Duncan, G., Lambie, D.G. and Johnson, R.H. Ventilatory responses to sustained static forearm exercise in man. New Zealand Med. Journal...1978, 88(618), 169. KEYWORDS: Static exercise , ventilatory responses . METHODS: Five healthy subjects were used to study the stimulus for

Breathing mechanics during exercise with added dead space reflect mechanisms of ventilatory control.

PubMed

Wood, Helen E; Mitchell, Gordon S; Babb, Tony G

2009-09-30

Small increases in external dead space (V(D)) augment the exercise ventilatory response via a neural mechanism known as short-term modulation (STM). We hypothesized that breathing mechanics would differ during exercise, increased V(D) and STM. Men were studied at rest and during cycle exercise (10-50W) without (Control) and with added V(D) (200-600ml). With added V(D), V(T) increased via increased end-inspiratory lung volume (EILV), with no change in end-expiratory lung volume (EELV), indicating recruitment of inspiratory muscles only. With exercise, V(T) increased via both decreased EELV and increased EILV, indicating recruitment of both expiratory and inspiratory muscles. A significant interaction between the effects of exercise and V(D) on mean inspiratory flow indicated that the augmented exercise ventilatory response with added V(D) (i.e. STM) resulted from increased drive to the inspiratory muscles. These results reveal different patterns of respiratory muscle recruitment among experimental conditions. Hence, we conclude that fundamental differences exist in the neural control of ventilatory responses during exercise, increased V(D) and STM.

NIRS-based noninvasive cerebrovascular regulation assessment

NASA Astrophysics Data System (ADS)

Miller, S.; Richmond, I.; Borgos, J.; Mitra, K.

2016-03-01

Alterations to cerebral blood flow (CBF) have been implicated in diverse neurological conditions, including mild traumatic brain injury, microgravity induced intracranial pressure (ICP) increases, mild cognitive impairment, and Alzheimer's disease. Near infrared spectroscopy (NIRS)-measured regional cerebral tissue oxygen saturation (rSO2) provides an estimate of oxygenation of the interrogated cerebral volume that is useful in identifying trends and changes in oxygen supply to cerebral tissue and has been used to monitor cerebrovascular function during surgery and ventilation. In this study, CO2-inhalation-based hypercapnic breathing challenges were used as a tool to simulate CBF dysregulation, and NIRS was used to monitor the CBF autoregulatory response. A breathing circuit for the selective administration of CO2-compressed air mixtures was designed and used to assess CBF regulatory responses to hypercapnia in 26 healthy young adults using non-invasive methods and real-time sensors. After a 5 or 10 minute baseline period, 1 to 3 hypercapnic challenges of 5 or 10 minutes duration were delivered to each subject while rSO2, partial pressure of end tidal CO2 (PETCO2), and vital signs were continuously monitored. Change in rSO2 measurements from pre- to intrachallenge (ΔrSO2) detected periods of hypercapnic challenges. Subjects were grouped into three exercise factor levels (hr/wk), 1: 0, 2:>0 and <10, and 3:>10. Exercise factor level 3 subjects showed significantly greater ΔrSO2 responses to CO2 challenges than level 2 and 1 subjects. No significant difference in ΔPETCO2 existed between these factor levels. Establishing baseline values of rSO2 in clinical practice may be useful in early detection of CBF changes.

Development of an Atlas of Strengths and Establishment of an Appropriate Model Structure

DTIC Science & Technology

1981-11-01

exercise hyperaemic response was greater for a given duration of contraction in water at 34 and 42*C than at lower temperatures. The rate of blood flow...Lambie, D.G. and Johnson, R.H. Ventilatory responses to sustained static forearm exercise in man. New Zealand Med. Journal; 1978, 88(618), 169...KEYWORDS: Static exercise , ventilatory responses . METHODS: Five healthy subjects were used to study the stimulus for hyperventilation which occurs during

Effect of atenolol on ventilatory and cardiac function in asthma.

PubMed Central

Vilsvik, J S; Schaanning, J

1976-01-01

The effects on ventilatory and cardiac function of atenolol, a new cardioselective beta-adrenoceptor blocking agent, were compared with those of practolol in a double-blind trial in 12 patients with asthma. Both drugs impaired ventilatory function--atenolol insignificantly and practolol significantly. Atenolol was if anything more cardioselective than practolol. Neither drug interfered significantly with the bronchodilator response to inhaled isoprenaline. Atenolol is suitable for use in patients for whom practolol would formerly have been chosen because of its cardioselectivity. PMID:8188

Arousal from sleep does not lead to reduced dilator muscle activity or elevated upper airway resistance on return to sleep in healthy individuals.

PubMed

Jordan, Amy S; Cori, Jennifer M; Dawson, Andrew; Nicholas, Christian L; O'Donoghue, Fergal J; Catcheside, Peter G; Eckert, Danny J; McEvoy, R Doug; Trinder, John

2015-01-01

To compare changes in end-tidal CO2, genioglossus muscle activity and upper airway resistance following tone-induced arousal and the return to sleep in healthy individuals with small and large ventilatory responses to arousal. Observational study. Two sleep physiology laboratories. 35 men and 25 women with no medical or sleep disorders. Auditory tones to induce 3-s to 15-s cortical arousals from sleep. During arousal from sleep, subjects with large ventilatory responses to arousal had higher ventilation (by analytical design) and tidal volume, and more marked reductions in the partial pressure of end-tidal CO2 compared to subjects with small ventilatory responses to arousal. However, following the return to sleep, ventilation, genioglossus muscle activity, and upper airway resistance did not differ between high and low ventilatory response groups (Breath 1 on return to sleep: ventilation 6.7±0.4 and 5.5±0.3 L/min, peak genioglossus activity 3.4%±1.0% and 4.8%±1.0% maximum, upper airway resistance 4.7±0.7 and 5.5±1.0 cm H2O/L/s, respectively). Furthermore, dilator muscle activity did not fall below the pre-arousal sleeping level and upper airway resistance did not rise above the pre-arousal sleeping level in either group for 10 breaths following the return to sleep. Regardless of the magnitude of the ventilatory response to arousal from sleep and subsequent reduction in PETCO2, healthy individuals did not develop reduced dilator muscle activity nor increased upper airway resistance, indicative of partial airway collapse, on the return to sleep. These findings challenge the commonly stated notion that arousals predispose to upper airway obstruction. © 2014 Associated Professional Sleep Societies, LLC.

Divers revisited: The ventilatory response to carbon dioxide in experienced scuba divers.

PubMed

Earing, Christopher Matthew Norton; McKeon, Damian John; Kubis, Hans-Peter

2014-05-01

To investigate the ventilatory response to CO2 in hyperoxia, hypoxia, and during exercise amongst experienced scuba divers and matched controls. Two studies were performed. The first investigated the CO2 sensitivity in rest and exercise using CO2 rebreathing in hyperoxia at a workload typical for diving with divers (n = 11) and controls (n = 11). The second study examined the respiratory drive of divers (n = 10) and controls (n = 10) whilst breathing four different gas mixtures balanced with N2 (ambient air; 25% O2/6% CO2; 13% O2; 13% O2/6% CO2) to assess the combined response to hypercapnia and moderate hypoxia. Exercise at a load typical for diving was found to have no effect on the ventilatory sensitivity to CO2 in divers (rest: 1.49 ± 0.33; exercise: 1.22 ± 0.55 [l/min × mmHg(-1)]) and controls (rest: 2.08 ± 0.71; exercise: 2.05 ± 0.98 [l/min × mmHg(-1)]) while differences in sensitivity remained between the groups. Inhalation of the four gas mixtures revealed the tested oxygen pressures caused no significant alteration in the ventilatory sensitivity to CO2 in divers and controls. Experienced divers possess a lower ventilatory response to CO2 which was not affected by exercise or the tested oxygen pressures suggesting a dominant adaptation of central CO2 sensitivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gender considerations in ventilatory and metabolic development in rats: special emphasis on the critical period

PubMed Central

LIU, QIULI; WONG-RILEY, MARGARET T.T

2013-01-01

In rats, a critical period exists around postnatal day (P) 12-13, when an imbalance between heightened inhibition and suppressed excitation led to a weakened ventilatory and metabolic response to acute hypoxia. An open question was whether the two genders follow the same or different developmental trends throughout the first 3 postnatal weeks and whether the critical period exists in one or both genders. The present large-scale, in-depth ventilatory and metabolic study was undertaken to address this question. Our data indicated that: 1) the ventilatory and metabolic rates in both normoxia and acute hypoxia were comparable between the two genders from P0 to P21; thus, gender was never significant as a main effect; and 2) the age effect was highly significant in all parameters studies for both genders, and both genders exhibited a significantly weakened response to acute hypoxia during the critical period. Thus, the two genders have comparable developmental trends, and the critical period exists in both genders in rats. PMID:23797186

Alteration by hyperoxia of ventilatory dynamics during sinusoidal work.

PubMed

Casaburi, R; Stremel, R W; Whipp, B J; Beaver, W L; Wasserman, K

1980-06-01

The effects of hyperoxia on ventilatory and gas exchange dynamics were studied utilizing sinusoidal work rate forcings. Five subjects exercised on 14 occasions on a cycle ergometer for 30 min with a sinusoidally varying work load. Tests were performed at seven frequencies of work load during air or 100% O2 inspiration. From the breath-by-breath responses to these tests, dynamic characteristics were analyzed by extracting the mean level, amplitude of oscillation, and phase lag for each six variables with digital computer techniques. Calculation of the time constant (tau) of the ventilatory responses demonstrated that ventilatory kinetics were slower during hyperoxia than during normoxia (P less than 0.025; avg 1.56 and 1.13 min, respectively). Further, for identical work rate fluctuations, end-tidal CO2 tension fluctuations were increased by hyperpoxia. Ventilation during hyperoxia is slower to respond to variations in the level of metabolically produced CO2, presumably because hyperoxia attenuates carotid body output; the arterial CO2 tension is consequently less tightly regulated.

Prefrontal cortex haemodynamics and affective responses during exercise: a multi-channel near infrared spectroscopy study.

PubMed

Tempest, Gavin D; Eston, Roger G; Parfitt, Gaynor

2014-01-01

The dose-response effects of the intensity of exercise upon the potential regulation (through top-down processes) of affective (pleasure-displeasure) responses in the prefrontal cortex during an incremental exercise protocol have not been explored. This study examined the functional capacity of the prefrontal cortex (reflected by haemodynamics using near infrared spectroscopy) and affective responses during exercise at different intensities. Participants completed an incremental cycling exercise test to exhaustion. Changes (Δ) in oxygenation (O2Hb), deoxygenation (HHb), blood volume (tHb) and haemoglobin difference (HbDiff) were measured from bilateral dorsal and ventral prefrontal areas. Affective responses were measured every minute during exercise. Data were extracted at intensities standardised to: below ventilatory threshold, at ventilatory threshold, respiratory compensation point and the end of exercise. During exercise at intensities from ventilatory threshold to respiratory compensation point, ΔO2Hb, ΔHbDiff and ΔtHb were greater in mostly ventral than dorsal regions. From the respiratory compensation point to the end of exercise, ΔO2Hb remained stable and ΔHbDiff declined in dorsal regions. As the intensity increased above the ventilatory threshold, inverse associations between affective responses and oxygenation in (a) all regions of the left hemisphere and (b) lateral (dorsal and ventral) regions followed by the midline (ventral) region in the right hemisphere were observed. Differential activation patterns occur within the prefrontal cortex and are associated with affective responses during cycling exercise.

Prefrontal Cortex Haemodynamics and Affective Responses during Exercise: A Multi-Channel Near Infrared Spectroscopy Study

PubMed Central

Tempest, Gavin D.; Eston, Roger G.; Parfitt, Gaynor

2014-01-01

The dose-response effects of the intensity of exercise upon the potential regulation (through top-down processes) of affective (pleasure-displeasure) responses in the prefrontal cortex during an incremental exercise protocol have not been explored. This study examined the functional capacity of the prefrontal cortex (reflected by haemodynamics using near infrared spectroscopy) and affective responses during exercise at different intensities. Participants completed an incremental cycling exercise test to exhaustion. Changes (Δ) in oxygenation (O2Hb), deoxygenation (HHb), blood volume (tHb) and haemoglobin difference (HbDiff) were measured from bilateral dorsal and ventral prefrontal areas. Affective responses were measured every minute during exercise. Data were extracted at intensities standardised to: below ventilatory threshold, at ventilatory threshold, respiratory compensation point and the end of exercise. During exercise at intensities from ventilatory threshold to respiratory compensation point, ΔO2Hb, ΔHbDiff and ΔtHb were greater in mostly ventral than dorsal regions. From the respiratory compensation point to the end of exercise, ΔO2Hb remained stable and ΔHbDiff declined in dorsal regions. As the intensity increased above the ventilatory threshold, inverse associations between affective responses and oxygenation in (a) all regions of the left hemisphere and (b) lateral (dorsal and ventral) regions followed by the midline (ventral) region in the right hemisphere were observed. Differential activation patterns occur within the prefrontal cortex and are associated with affective responses during cycling exercise. PMID:24788166

Ibuprofen does not reverse ventilatory acclimatization to chronic hypoxia.

PubMed

De La Zerda, D J; Stokes, J A; Do, J; Go, A; Fu, Z; Powell, F L

2017-07-27

Ventilatory acclimatization to hypoxia involves an increase in the acute hypoxic ventilatory response that is blocked by non-steroidal anti-inflammatory drugs administered during sustained hypoxia. We tested the hypothesis that inflammatory signals are necessary to sustain ventilatory acclimatization to hypoxia once it is established. Adult, rats were acclimatized to normoxia or chronic hypoxia (CH, [Formula: see text] =70Torr) for 11-12days and treated with ibuprofen or saline for the last 2days of hypoxia. Ventilation, metabolic rate, and arterial blood gas responses to O 2 and CO 2 were not affected by ibuprofen after acclimatization had been established. Immunohistochemistry and image analysis showed acute (1h) hypoxia activated microglia in a medullary respiratory center (nucleus tractus solitarius, NTS) and this was blocked by ibuprofen administered from the beginning of hypoxic exposure. Microglia returned to the control state after 7days of CH and were not affected by ibuprofen administered for 2 more days of CH. In contrast, NTS astrocytes were activated by CH but not acute hypoxia and activation was not reversed by administering ibuprofen for the last 2days of CH. Hence, ibuprofen cannot reverse ventilatory acclimatization or astrocyte activation after they have been established by sustained hypoxia. The results are consistent with a model for microglia activation or other ibuprofen-sensitive processes being necessary for the induction but not maintenance of ventilatory acclimatization to hypoxia. Copyright © 2017 Elsevier B.V. All rights reserved.

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

PubMed Central

Pamenter, Matthew E.; Powell, Frank L.

2016-01-01

Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields. PMID:27347896

Consequences of intrauterine growth restriction on ventilatory and thermoregulatory responses to asphyxia and hypercapnia in the newborn guinea-pig.

PubMed

Tolcos, Mary; Rees, Sandra; McGregor, Hugh; Walker, David

2002-01-01

The purpose of this study was to determine the effects of prenatal growth restriction on the ventilatory and thermoregulatory responses to asphyxia and hypercapnia in the newborn guinea-pig. Spontaneously growth-restricted (SGR) animals born to unoperated dams, and growth-retarded (GR) neonates born to dams in which a uterine artery had been ligated at mid gestation, were studied and compared with control neonates. Ventilatory responses to progressive asphyxia and steady-state hypercapnia were tested at 3-6 days of age using a barometric plethysmograph. The animals were then killed and the brains prepared for histological and immunohistochemical analysis. During progressive asphyxia, SGR neonates (n = 5) had a significantly increased minute ventilation compared with both control (n = 6) and GR (n = 5) neonates. Rectal temperature fell significantly in GR and SGR neonates after progressive asphyxia, but was unchanged in control neonates. The ventilatory responses to steady-state hypercapnia were not different in the GR, SGR and control neonates. The immunoreactive expression of glial fibrillary acidic protein, tyrosine hydroxylase, substance P and met-enkephalin in the medulla was also not different between the three groups. It was concluded that prenatal growth restriction is associated with alterations in the respiratory and thermoregulatory responses to asphyxia and hypercapnia, with greater effects observed when in utero growth restriction arises spontaneously, compared with that produced experimentally over approximately the last half of gestation.

Role of vagal afferents in the ventilatory response to naloxone during loaded breathing in the rabbit.

PubMed

Delpierre, S; Pugnat, C; Duté, N; Jammes, Y

1995-02-15

It was previously shown that inspiratory resistive loading (IRL) increases the cerebrospinal fluid (CSF) level of beta endorphin in awake goats, and also that the slower ventilation induced by injection of this substance into the CSF of anesthetized dogs is suppressed after vagotomy. In the present study, performed on anesthetized rabbits, we evaluated the part played by vagal afferents in the ventilatory response to IRL after opioid receptor blockade by naloxone. During unloaded breathing, naloxone injection did not modify baseline ventilation. Conversely, naloxone partially reversed IRL-induced hypoventilation through an increase in respiratory rate. This effect was abolished after either vagotomy or cold blockade of large vagal fibers, but it persisted after procaine blockade of thin vagal fibers. These results suggest that pulmonary stretch receptors, which are connected to some large vagal afferent fibers, would play a major role in the ventilatory response to IRL under opioid receptor inhibition.

Ventilatory and circulatory responses at the onset of exercise in man following heart or heart-lung transplantation.

PubMed Central

Banner, N; Guz, A; Heaton, R; Innes, J A; Murphy, K; Yacoub, M

1988-01-01

1. Ventilatory and cardiovascular responses to the onset of voluntary and electrically induced leg exercise were studied in six patients following heart transplantation and five following heart-lung transplantation; the results were compared between the patient groups and also with responses from a group of normal subjects. 2. Oxygen consumption, carbon dioxide production and ventilation and its components were measured over two 30 s periods prior to, and two 30 s periods following, the onset of exercise. Relative changes in stroke volume and cardiac output were derived from ensemble-averaged Doppler measurements of ascending aortic blood velocity over the same 30 s periods. 3. None of the groups of subjects showed any significant differences in responses to voluntary exercise compared to electrically induced exercise of similar work pattern and intensity. 4. Compared to normal controls, the transplanted subjects showed higher resting heart rates which did not increase at the onset of exercise; stroke volume increased, but less than in the normal subjects. The resulting cardiac output increases in the transplanted subjects were minimal compared to the normal subjects. 5. Ventilation and oxygen uptake increased immediately and with similar magnitude in all three groups. 6. These results show that in the same individual it is possible to have an appropriate ventilatory response to the onset of exercise in the presumed absence of a normal corticospinal input to the exercising muscles (electrically induced exercise) and afferent neural information from the lungs and heart, and in the absence of a normal circulatory response to exercise. The mechanisms underlying this ventilatory response remain undetermined. PMID:3136247

Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans

PubMed Central

Basaran, Kemal Erdem; Villongco, Michael; Ho, Baran; Ellis, Erika; Zarndt, Rachel; Antonova, Julie; Hopkins, Susan R.; Powell, Frank L.

2016-01-01

Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR) that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400mg every 8 hrs) or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m). Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O2 saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O2-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease. PMID:26726885

Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans.

PubMed

Basaran, Kemal Erdem; Villongco, Michael; Ho, Baran; Ellis, Erika; Zarndt, Rachel; Antonova, Julie; Hopkins, Susan R; Powell, Frank L

2016-01-01

Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR) that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400 mg every 8 hrs) or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m). Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O2 saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O2-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease.

Studies of Ventilatory Capacity and Histamine Response during Exposure to Isocyanate Vapour in Polyurethane Foam Manufacture

PubMed Central

Gandevia, Bryan

1963-01-01

Complaints of respiratory symptoms amongst workers in a factory using isocyanate to produce polyurethane foam led to a study of changes in ventilatory capacity in the course of several working days. Mean decreases of the order of 0·181. were observed in the forced expiratory volume at one second in 15 employees during each of three normal working shifts. No significant change occurred on days when a process involving the liberation of isocyanate was stopped, or when the men were given an oral aminophylline compound prophylactically. An aerosol of isoprenaline failed to reverse the decrease in ventilatory capacity observed during one normal working day. Approximately half the subjects studied were found to show increased bronchial sensitivity to a histamine aerosol; all were smokers, whereas none of the non-smokers showed a significant (over 10%) reduction in ventilatory capacity after histamine. Smokers and/or positive histamine reactors tended to show a greater decrease in ventilatory capacity during a working day than non-smokers or non-reactors. The present findings, which confirm clinical reports of adverse respiratory effects of isocyanate in low concentrations, are compared with other studies of ventilatory capacity during occupational exposure to respiratory irritants. PMID:14046157

Oxygen therapy devices and portable ventilators for improved physical activity in daily life in patients with chronic respiratory disease.

PubMed

Furlanetto, Karina Couto; Pitta, Fabio

2017-02-01

Patients with hypoxemia and chronic respiratory failure may need to use oxygen therapy to correct hypoxemia and to use ventilatory support to augment alveolar ventilation, reverse abnormalities in blood gases (in particular hypercapnia) and reduce the work of breathing. Areas covered: This narrative review provides an overview on the use of oxygen therapy devices or portable ventilators for improved physical activity in daily life (PADL) as well as discusses the issue of lower mobility in daily life among stable patients with chronic respiratory disease who present indication for long-term oxygen therapy (LTOT) or home-based noninvasive ventilation (NIV). A literature review of these concepts was performed by using all related search terms. Expert commentary: Technological advances led to the development of light and small oxygen therapy devices and portable ventilators which aim to facilitate patients' mobility and ambulation. However, the day-by-day dependence of a device may reduce mobility and partially impair patients' PADL. Nocturnal NIV implementation in hypercapnic patients seems promising to improve PADL. The magnitude of their equipment-related physical inactivity is underexplored up to this moment and more long-term randomized clinical trials and meta-analysis examining the effects of ambulatory oxygen and NIV on PADL are required.

Pathogenesis of central and complex sleep apnoea.

PubMed

Orr, Jeremy E; Malhotra, Atul; Sands, Scott A

2017-01-01

Central sleep apnoea (CSA) - the temporary absence or diminution of ventilatory effort during sleep - is seen in a variety of forms including periodic breathing in infancy and healthy adults at altitude and Cheyne-Stokes respiration in heart failure. In most circumstances, the cyclic absence of effort is paradoxically a consequence of hypersensitive ventilatory chemoreflex responses to oppose changes in airflow, that is elevated loop gain, leading to overshoot/undershoot ventilatory oscillations. Considerable evidence illustrates overlap between CSA and obstructive sleep apnoea (OSA), including elevated loop gain in patients with OSA and the presence of pharyngeal narrowing during central apnoeas. Indeed, treatment of OSA, whether via continuous positive airway pressure (CPAP), tracheostomy or oral appliances, can reveal CSA, an occurrence referred to as complex sleep apnoea. Factors influencing loop gain include increased chemosensitivity (increased controller gain), reduced damping of blood gas levels (increased plant gain) and increased lung to chemoreceptor circulatory delay. Sleep-wake transitions and pharyngeal dilator muscle responses effectively raise the controller gain and therefore also contribute to total loop gain and overall instability. In some circumstances, for example apnoea of infancy and central congenital hypoventilation syndrome, central apnoeas are the consequence of ventilatory depression and defective ventilatory responses, that is low loop gain. The efficacy of available treatments for CSA can be explained in terms of their effects on loop gain, for example CPAP improves lung volume (plant gain), stimulants reduce the alveolar-inspired PCO 2 difference and supplemental oxygen lowers chemosensitivity. Understanding the magnitude of loop gain and the mechanisms contributing to instability may facilitate personalized interventions for CSA. © 2016 Asian Pacific Society of Respirology.

Blockade of phosphodiesterase 4 reverses morphine-induced ventilatory disturbance without loss of analgesia.

PubMed

Kimura, Satoko; Ohi, Yoshiaki; Haji, Akira

2015-04-15

Ventilatory disturbance is a fatal side-effect of opioid analgesics. Separation of analgesia from ventilatory depression is important for therapeutic use of opioids. It has been suggested that opioid-induced ventilatory depression results from a decrease in adenosine 3',5'-cyclic monophosphate content in the respiratory-related neurons. Therefore, we examined the effects of caffeine, a methylxanthine non-selective phosphodiesterase (PDE) inhibitor with adenosine antagonistic activity, and rolipram, a racetam selective PDE4 inhibitor, on ventilatory depression induced by morphine. Spontaneous ventilation and paw withdrawal responses to nociceptive thermal stimulation were measured in anesthetized rats simultaneously. The efferent discharge of the phrenic nerve was recorded in anesthetized, vagotomized, paralyzed and artificially ventilated rats. Rolipram (0.1 and 0.3 mg/kg, i.v.) and caffeine (3.0 and 10.0 mg/kg, i.v.) relieved morphine (1.0 mg/kg, i.v.)-induced ventilatory depression but had no discernible effect on its analgesic action. Rolipram (0.3 and 1.0 mg/kg, i.v.) and caffeine (10.0 and 20.0 mg/kg, i.v.) recovered morphine (3.0 mg/kg, i.v.)-induced prolongation and flattening of inspiratory discharge in the phrenic nerve. Inhibition of PDE4 may be a possible approach for overcoming morphine-induced ventilatory depression without loss of analgesia. Copyright © 2015 Elsevier Inc. All rights reserved.

Chronic Intermittent Hypoxia Blunts the Expression of Ventilatory Long Term Facilitation in Sleeping Rats.

PubMed

Edge, Deirdre; O'Halloran, Ken D

2015-01-01

We have previously reported that chronic intermittent hypoxia (CIH), a central feature of human sleep-disordered breathing, causes respiratory instability in sleeping rats (Edge D, Bradford A, O'halloran KD. Adv Exp Med Biol 758:359-363, 2012). Long term facilitation (LTF) of respiratory motor outputs following exposure to episodic, but not sustained, hypoxia has been described. We hypothesized that CIH would enhance ventilatory LTF during sleep. We examined the effects of 3 and 7 days of CIH exposure on the expression of ventilatory LTF in sleeping rats. Adult male Wistar rats were exposed to 20 cycles of normoxia and hypoxia (5 % O(2) at nadir; SaO(2) ~ 80 %) per hour, 8 h per day for 3 or 7 consecutive days (CIH, N = 7 per group). Corresponding sham groups (N = 7 per group) were subjected to alternating cycles of air under identical experimental conditions in parallel. Following gas exposures, breathing during sleep was assessed in unrestrained, unanaesthetized animals using the technique of whole-body plethysmography. Rats were exposed to room air (baseline) and then to an acute IH (AIH) protocol consisting of alternating periods of normoxia (7 min) and hypoxia (FiO(2) 0.1, 5 min) for 10 cycles. Breathing was monitored during the AIH exposure and for 1 h in normoxia following AIH exposure. Baseline ventilation was elevated after 3 but not 7 days of CIH exposure. The hypoxic ventilatory response was equivalent in sham and CIH animals after 3 days but ventilatory responses to repeated hypoxic challenges were significantly blunted following 7 days of CIH. Minute ventilation was significantly elevated following AIH exposure compared to baseline in sham but not in CIH exposed animals. LTF, determined as the % increase in minute ventilation from baseline following AIH exposure, was significantly blunted in CIH exposed rats. In summary, CIH leads to impaired ventilatory responsiveness to AIH. Moreover, CIH blunts ventilatory LTF. The physiological significance of ventilatory LTF is context-dependent but it is reasonable to consider that it can potentially destabilize respiratory control, in view of the potential for LTF to give rise to hypocapnia. CIH-induced blunting of LTF may represent a compensatory mechanism subserving respiratory homeostasis. Our results suggest that CIH-induced increase in apnoea index (Edge D, Bradford A, O'halloran KD. Adv Exp Med Biol 758:359-363, 2012) is not related to enhanced ventilatory LTF. We conclude that the mature adult respiratory system exhibits plasticity and metaplasticity with potential consequences for the control of respiratory homeostasis. Our results may have implications for human sleep apnoea.

Response characteristics of an aquatic biomonitor used for rapid toxicity detection.

PubMed

van der Schalie, W H; Shedd, T R; Widder, M W; Brennan, L M

2004-01-01

The response characteristics of an aquatic biomonitor that detects toxicity by monitoring changes in bluegill (Lepomis macrochirus Rafinesque) ventilatory and movement patterns were evaluated in single chemical laboratory studies at concentrations near the 96-h LC(50) concentration and at the EILATox-Oregon Workshop in sequential tests of multiple unknown samples. Baseline data collected prior to exposure allows each fish to serve as its own control. When at least 70% of exposed fish exhibit ventilatory or movement parameters significantly different from baseline observations, a group alarm is declared. In the laboratory studies, the aquatic biomonitor responded to the majority of chemicals at the 96-h lc(50) within an hour or less, although substantially higher response times were found for malathion and pentachlorophenol. Workshop tests of single chemical concentrations presented as blind samples were consistent with the laboratory test results. There were no alarms under control conditions in any test. Although data are limited, the aquatic biomonitor appears to respond more rapidly to chemicals causing membrane irritation, narcosis or polar narcosis than to acetylcholinesterase inhibitors or oxidative phosphorylation uncouplers. All four monitored parameters (ventilatory rate, cough rate, ventilatory depth and movement) contributed to identification of first alarms at acutely toxic levels. Understanding these response patterns can be useful in data interpretation for biomonitor applications such as surface water monitoring for watershed protection, wastewater treatment plant effluent monitoring or source water monitoring for drinking water protection. Copyright (c) 2004 John Wiley & Sons, Ltd.

[Respiratory hypercapnic-hypoxic training is an effective component of complex therapy of polyneuropathy in children with diabetes type 1].

PubMed

Smirnov, K V; Smirnova, Yu V; Kulikov, V P; Nazarkina, O M

2018-01-01

To study the effectiveness of respiratory hypercapnic-hypoxic training in complex treatment of neuropathy due to diabetes type 1. Fifty children, 31 girls and 19 boys, were examined. The inclusion criteria were the presence of polyneuropathy, verified on the basis of clinical data and electromyographic changes. The patients were divided into 2 groups: the main group (n=25, 15 girls and 10 boys, mean age 12.9±1.8 years (M±SD) and the comparison group (n=25, 16 girls and 9 boys, mean age 13.2±2.0 years). Patients of the main group, along with standard therapy received respiratory hypercapnic-hypoxic training. The positive clinical and neurophysiological dynamics was noted in both groups, with more significant changes in children after respiratory training. Hypercapnic exercises significantly contribute to the pathogenetic therapy of diabetes mellitus and polyneuropathy in this disease, have a significant clinical effects reducing serum concentrations of fasting glucose and severity of neurological deficit scores on the NIS-LL, increasing the speed of conduction of excitation through the nerves, reducing the residual latency of EMG activity.

Antenatal smoking and substance-misuse, infant and newborn response to hypoxia.

PubMed

Ali, Kamal; Rosser, Thomas; Bhat, Ravindra; Wolff, Kim; Hannam, Simon; Rafferty, Gerrard F; Greenough, Anne

2017-05-01

To determine at the peak age for sudden infant death syndrome (SIDS) the ventilatory response to hypoxia of infants whose mothers substance misused in pregnancy (SM infants), or smoked during pregnancy (S mothers) and controls whose mothers neither substance misused or smoked. In addition, we compared the ventilatory response to hypoxia during the neonatal period and peak age of SIDS. Infants of S or SM mothers compared to control infants would have a poorer ventilatory response to hypoxia at the peak age of SIDS. Prospective, observational study. Twelve S; 12 SM and 11 control infants were assessed at 6-12 weeks of age and in the neonatal period. Changes in minute volume, oxygen saturation, heart rate, and end tidal carbon dioxide levels on switching from breathing room air to 15% oxygen were assessed. Maternal and infant urine samples were tested for cotinine, cannabinoids, opiates, amphetamines, methadone, cocaine, and benzodiazepines. The S and SM infants had a greater decline in minute volume (P = 0.037, P = 0.016, respectively) and oxygen saturation (P = 0.031) compared to controls. In all groups, the magnitude of decline in minute volume in response to hypoxia was higher in the neonatal period compared to at 6-12 weeks (P < 0.001). Both maternal substance misuse and smoking were associated with an impaired response to a hypoxic challenge at the peak age for SIDS. The hypoxic ventilatory decline was more marked in the neonatal period compared to the peak age for SIDS indicating a maturational effect. Pediatr Pulmonol. 2017;52:650-655. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Prenatal nicotinic exposure augments cardiorespiratory responses to activation of bronchopulmonary C-fibers

PubMed Central

Zhuang, Jianguo; Zhao, Lei; Zang, Na

2015-01-01

Rat pups prenatally exposed to nicotine (PNE) present apneic (lethal ventilatory arrest) responses during severe hypoxia. To clarify whether these responses are of central origin, we tested PNE effects on ventilation and diaphragm electromyography (EMGdi) during hypoxia in conscious rat pups. PNE produced apnea (lethal ventilatory arrest) identical to EMGdi silencing during hypoxia, indicating a central origin of this apneic response. We further asked whether PNE would sensitize bronchopulmonary C-fibers (PCFs), a key player in generating central apnea, with increase of the density and transient receptor potential cation channel subfamily V member 1 (TRPV1) expression of C-fibers/neurons in the nodose/jugular (N/J) ganglia and neurotrophic factors in the airways and lungs. We compared 1) ventilatory and pulmonary C-neural responses to right atrial bolus injection of capsaicin (CAP, 0.5 μg/kg), 2) bronchial substance P-immunoreactive (SP-IR) fiber density, 3) gene and protein expressions of TRPV1 in the ganglia, and 4) nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) protein in bronchoalveolar lavage fluid (BALF) and TrkA and TrkB genes in the ganglia between control and PNE pups. PNE markedly strengthened the PCF-mediated apneic response to CAP via increasing pulmonary C-neural sensitivity. PNE also enhanced bronchial SP-IR fiber density and N/J ganglia neural TRPV1 expression associated with increased gene expression of TrkA in the N/G ganglia and decreased NGF and BDNF in BALF. Our results suggest that PNE enhances PCF sensitivity likely through increasing PCF density and TRPV1 expression via upregulation of neural TrkA and downregulation of pulmonary BDNF, which may contribute to the PNE-promoted central apnea (lethal ventilatory arrest) during hypoxia. PMID:25747962

Heart rate response during a simulated Olympic boxing match is predominantly above ventilatory threshold 2: a cross sectional study

PubMed Central

de Lira, Claudio Andre Barbosa; Peixinho-Pena, Luiz Fernando; Vancini, Rodrigo Luiz; de Freitas Guina Fachina, Rafael Júlio; de Almeida, Alexandre Aparecido; Andrade, Marília dos Santos; da Silva, Antonio Carlos

2013-01-01

The present study aimed to describe heart rate (HR) responses during a simulated Olympic boxing match and examine physiological parameters of boxing athletes. Ten highly trained Olympic boxing athletes (six men and four women) performed a maximal graded exercise test on a motorized treadmill to determine maximal oxygen uptake (52.2 mL · kg−1 · min−1 ± 7.2 mL · kg−1 · min−1) and ventilatory thresholds 1 and 2. Ventilatory thresholds 1 and 2 were used to classify the intensity of exercise based on respective HR during a boxing match. In addition, oxygen uptake (V̇O2) was estimated during the match based on the HR response and the HR-V̇O2 relationship obtained from a maximal graded exercise test for each participant. On a separate day, participants performed a boxing match lasting three rounds, 2 minutes each, with a 1-minute recovery period between each round, during which HR was measured. In this context, HR and V̇O2 were above ventilatory threshold 2 during 219.8 seconds ± 67.4 seconds. There was an increase in HR and V̇O2 as a function of round (round 3 < round 2 < round 1, P < 0.0001). These findings may direct individual training programs for boxing practitioners and other athletes. PMID:24379723

Heart rate response during a simulated Olympic boxing match is predominantly above ventilatory threshold 2: a cross sectional study.

PubMed

de Lira, Claudio Andre Barbosa; Peixinho-Pena, Luiz Fernando; Vancini, Rodrigo Luiz; de Freitas Guina Fachina, Rafael Júlio; de Almeida, Alexandre Aparecido; Andrade, Marília Dos Santos; da Silva, Antonio Carlos

2013-01-01

The present study aimed to describe heart rate (HR) responses during a simulated Olympic boxing match and examine physiological parameters of boxing athletes. Ten highly trained Olympic boxing athletes (six men and four women) performed a maximal graded exercise test on a motorized treadmill to determine maximal oxygen uptake (52.2 mL · kg(-1) · min(-1) ± 7.2 mL · kg(-1) · min(-1)) and ventilatory thresholds 1 and 2. Ventilatory thresholds 1 and 2 were used to classify the intensity of exercise based on respective HR during a boxing match. In addition, oxygen uptake (V̇O2) was estimated during the match based on the HR response and the HR-V̇O2 relationship obtained from a maximal graded exercise test for each participant. On a separate day, participants performed a boxing match lasting three rounds, 2 minutes each, with a 1-minute recovery period between each round, during which HR was measured. In this context, HR and V̇O2 were above ventilatory threshold 2 during 219.8 seconds ± 67.4 seconds. There was an increase in HR and V̇O2 as a function of round (round 3 < round 2 < round 1, P < 0.0001). These findings may direct individual training programs for boxing practitioners and other athletes.

Determinants of ventilation and pulmonary artery pressure during early acclimatization to hypoxia in humans.

PubMed

Fatemian, Marzieh; Herigstad, Mari; Croft, Quentin P P; Formenti, Federico; Cardenas, Rosa; Wheeler, Carly; Smith, Thomas G; Friedmannova, Maria; Dorrington, Keith L; Robbins, Peter A

2016-03-01

Pulmonary ventilation and pulmonary arterial pressure both rise progressively during the first few hours of human acclimatization to hypoxia. These responses are highly variable between individuals, but the origin of this variability is unknown. Here, we sought to determine whether the variabilities between different measures of response to sustained hypoxia were related, which would suggest a common source of variability. Eighty volunteers individually underwent an 8-h isocapnic exposure to hypoxia (end-tidal P(O2)=55 Torr) in a purpose-built chamber. Measurements of ventilation and pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography were made during the exposure. Before and after the exposure, measurements were made of the ventilatory sensitivities to acute isocapnic hypoxia (G(pO2)) and hyperoxic hypercapnia, the latter divided into peripheral (G(pCO2)) and central (G(cCO2)) components. Substantial acclimatization was observed in both ventilation and PASP, the latter being 40% greater in women than men. No correlation was found between the magnitudes of pulmonary ventilatory and pulmonary vascular responses. For G(pO2), G(pCO2) and G(cC O2), but not the sensitivity of PASP to acute hypoxia, the magnitude of the increase during acclimatization was proportional to the pre-acclimatization value. Additionally, the change in G(pO2) during acclimatization to hypoxia correlated well with most other measures of ventilatory acclimatization. Of the initial measurements prior to sustained hypoxia, only G(pCO2) predicted the subsequent rise in ventilation and change in G(pO2) during acclimatization. We conclude that the magnitudes of the ventilatory and pulmonary vascular responses to sustained hypoxia are predominantly determined by different factors and that the initial G(pCO2) is a modest predictor of ventilatory acclimatization. © 2015 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Excess Ventilation in Chronic Obstructive Pulmonary Disease-Heart Failure Overlap. Implications for Dyspnea and Exercise Intolerance.

PubMed

Rocha, Alcides; Arbex, Flavio F; Sperandio, Priscilla A; Souza, Aline; Biazzim, Ligia; Mancuso, Frederico; Berton, Danilo C; Hochhegger, Bruno; Alencar, Maria Clara N; Nery, Luiz E; O'Donnell, Denis E; Neder, J Alberto

2017-11-15

An increased ventilatory response to exertional metabolic demand (high [Formula: see text]e/[Formula: see text]co 2 relationship) is a common finding in patients with coexistent chronic obstructive pulmonary disease and heart failure. We aimed to determine the mechanisms underlying high [Formula: see text]e/[Formula: see text]co 2 and its impact on operating lung volumes, dyspnea, and exercise tolerance in these patients. Twenty-two ex-smokers with combined chronic obstructive pulmonary disease and heart failure with reduced left ventricular ejection fraction undertook, after careful treatment optimization, a progressive cycle exercise test with capillary (c) blood gas collection. Regardless of the chosen metric (increased [Formula: see text]e-[Formula: see text]co 2 slope, [Formula: see text]e/[Formula: see text]co 2 nadir, or end-exercise [Formula: see text]e/[Formula: see text]co 2 ), ventilatory inefficiency was closely related to Pc CO 2 (r values from -0.80 to -0.84; P < 0.001) but not dead space/tidal volume ratio. Ten patients consistently maintained exercise Pc CO 2 less than or equal to 35 mm Hg (hypocapnia). These patients had particularly poor ventilatory efficiency compared with patients without hypocapnia (P < 0.05). Despite the lack of between-group differences in spirometry, lung volumes, and left ventricular ejection fraction, patients with hypocapnia had lower resting Pa CO 2 and lung diffusing capacity (P < 0.01). Excessive ventilatory response in this group was associated with higher exertional Pc O 2 . The group with hypocapnia, however, had worse mechanical inspiratory constraints and higher dyspnea scores for a given work rate leading to poorer exercise tolerance compared with their counterparts (P < 0.05). Heightened neural drive promoting a ventilatory response beyond that required to overcome an increased "wasted" ventilation led to hypocapnia and poor exercise ventilatory efficiency in chronic obstructive pulmonary disease-heart failure overlap. Excessive ventilation led to better arterial oxygenation but at the expense of earlier critical mechanical constraints and intolerable dyspnea.

Low Cardiorespiratory Fitness is Partially Linked to Ventilatory Factors in Obese Adolescents.

PubMed

Mendelson, Monique; Michallet, Anne-Sophie; Tonini, Julia; Favre-Juvin, Anne; Guinot, Michel; Wuyam, Bernard; Flore, Patrice

2016-02-01

To examine the role of ventilatory constraint on cardiorespiratory fitness in obese adolescents. Thirty obese adolescents performed a maximal incremental cycling exercise and were divided into 2 groups based on maximal oxygen uptake (VO2peak): those presenting low (L; n = 15; VO2peak: 72.9 ± 8.6% predicted) or normal (N; n = 15; VO2peak: 113.6 ± 19.2% predicted) cardiorespiratory fitness. Both were compared with a group of healthy controls (C; n = 20; VO2peak: 103.1 ± 11.2% predicted). Ventilatory responses were explored using the flow volume loop method. Cardiorespiratory fitness (VO2peak, in % predicted) was lower in L compared with C and N and was moderately associated with the percent predicted forced vital capacity (FVC) (r = .52; p < .05) in L. At peak exercise, end inspiratory point was lower in L compared with N and C (77.4 ± 8.1, 86.4 ± 7.7, and 89.9 ± 7.6% FVC in L, N, and C, respectively; p < .05), suggesting an increased risk of ventilatory constraint in L, although at peak exercise this difference could be attributed to the lower maximal ventilation in L. Forced vital capacity and ventilatory strategy to incremental exercise slightly differed between N and L. These results suggest a modest participation of ventilatory factors to exercise intolerance.

Arousal from Sleep Does Not Lead to Reduced Dilator Muscle Activity or Elevated Upper Airway Resistance on Return to Sleep in Healthy Individuals

PubMed Central

Jordan, Amy S.; Cori, Jennifer M.; Dawson, Andrew; Nicholas, Christian L.; O'Donoghue, Fergal J.; Catcheside, Peter G.; Eckert, Danny J.; McEvoy, R. Doug; Trinder, John

2015-01-01

Study Objectives: To compare changes in end-tidal CO2, genioglossus muscle activity and upper airway resistance following tone-induced arousal and the return to sleep in healthy individuals with small and large ventilatory responses to arousal. Design: Observational study. Setting: Two sleep physiology laboratories. Patients or Participants: 35 men and 25 women with no medical or sleep disorders. Interventions: Auditory tones to induce 3-s to 15-s cortical arousals from sleep. Measurements and Results: During arousal from sleep, subjects with large ventilatory responses to arousal had higher ventilation (by analytical design) and tidal volume, and more marked reductions in the partial pressure of end-tidal CO2 compared to subjects with small ventilatory responses to arousal. However, following the return to sleep, ventilation, genioglossus muscle activity, and upper airway resistance did not differ between high and low ventilatory response groups (Breath 1 on return to sleep: ventilation 6.7 ± 0.4 and 5.5 ± 0.3 L/min, peak genioglossus activity 3.4% ± 1.0% and 4.8% ± 1.0% maximum, upper airway resistance 4.7 ± 0.7 and 5.5 ± 1.0 cm H2O/L/s, respectively). Furthermore, dilator muscle activity did not fall below the pre-arousal sleeping level and upper airway resistance did not rise above the pre-arousal sleeping level in either group for 10 breaths following the return to sleep. Conclusions: Regardless of the magnitude of the ventilatory response to arousal from sleep and subsequent reduction in PETCO2, healthy individuals did not develop reduced dilator muscle activity nor increased upper airway resistance, indicative of partial airway collapse, on the return to sleep. These findings challenge the commonly stated notion that arousals predispose to upper airway obstruction. Citation: Jordan AS, Cori JM, Dawson A, Nicholas CL, O'Donoghue FJ, Catcheside PG, Eckert DJ, McEvoy RD, Trinder J. Arousal from sleep does not lead to reduced dilator muscle activity or elevated upper airway resistance on return to sleep in healthy individuals. SLEEP 2015;38(1):53–59. PMID:25325511

Ventilatory response to the onset of passive and active exercise in human subjects.

PubMed

Miyamura, M; Ishida, K; Yasuda, Y

1992-01-01

Ventilatory responses at the onset of passive and active exercise with different amount of exercising muscle mass were studied in 10 healthy male subjects. Four exercise tests were performed for each subject with appropriate intervals on the same day, i.e., two voluntary exercises of one leg or both legs and two passive exercises of one leg or both legs. Inspiratory minute volume (VI), end-tidal CO2 and O2 partial pressures (PETCO2, PETO2) were measured breath-by-breath using a hot-wire flowmeter, infrared CO2 analyzer, and a rapid O2 analyzer. Average values of VI were obtained from 5 breaths at rest preceding exercise and the first and second breaths after the onset of exercise. The ventilatory response to exercise was calculated as the difference (delta) between the mean of exercise VI and mean of resting VI. In this study, the PETCO2 decreased by about 0.5 Torr in four exercise tests, though the decrement of PETCO2 was not statistically significant. The average values and standard deviation of delta VI were 4.22 +/- 1.63 l/min for the one leg and 6.46 +/- 1.80 l/min for the two legs in the active exercise, and were 2.46 +/- 1.12 l/min for the one leg and 3.44 +/- 1.55 l/min for the two legs in the passive exercise, respectively. These results suggest that in awake conditions, the ventilatory response at the onset of passive or active exercise does not increase additively with the increasing amount of muscle mass being exercised.

Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling

PubMed Central

Dick, Thomas E.; Molkov, Yaroslav I.; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J.; Doyle, John; Scheff, Jeremy D.; Calvano, Steve E.; Androulakis, Ioannis P.; An, Gary; Vodovotz, Yoram

2012-01-01

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma. PMID:22783197

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): Response to ventilatory challenges.

PubMed

Carroll, Michael S; Patwari, Pallavi P; Kenny, Anna S; Brogadir, Cindy D; Stewart, Tracey M; Weese-Mayer, Debra E

2015-12-01

Hypoventilation is a defining feature of Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD), a rare respiratory and autonomic disorder. This chronic hypoventilation has been explained as the result of dysfunctional chemosensory control circuits, possibly affecting peripheral afferent input, central integration, or efferent motor control. However, chemosensory function has never been quantified in a cohort of ROHHAD patients. Therefore, the purpose of this study was to assess the response to awake ventilatory challenge testing in children and adolescents with ROHHAD. The ventilatory, cardiovascular and cerebrovascular responses in 25 distinct comprehensive physiological recordings from seven unique ROHHAD patients to three different gas mixtures were analyzed at breath-to-breath and beat-to-beat resolution as absolute measures, as change from baseline, or with derived metrics. Physiologic measures were recorded during a 3-min baseline period of room air, a 3-min gas exposure (of 100% O2; 95% O2, 5% CO2; or 14% O2, 7% CO2 balanced with N2), and a 3-min recovery period. An additional hypoxic challenge was conducted which consisted of either five or seven tidal breaths of 100% N2. While ROHHAD cases showed a diminished VT and inspiratory drive response to hypoxic hypercapnia and absent behavioral awareness of the physiologic compromise, most ventilatory, cardiovascular, and cerebrovascular measures were similar to those of previously published controls using an identical protocol, suggesting a mild chemosensory deficit. Nonetheless, the high mortality rate, comorbidity and physiological fragility of patients with ROHHAD demand continued clinical vigilance. © 2015 Wiley Periodicals, Inc.

Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling.

PubMed

Dick, Thomas E; Molkov, Yaroslav I; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J; Doyle, John; Scheff, Jeremy D; Calvano, Steve E; Androulakis, Ioannis P; An, Gary; Vodovotz, Yoram

2012-01-01

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma.

Effects of elevated oxygen and carbon dioxide partial pressures on respiratory function and cognitive performance.

PubMed

Gill, Matthew; Natoli, Michael J; Vacchiano, Charles; MacLeod, David B; Ikeda, Keita; Qin, Michael; Pollock, Neal W; Moon, Richard E; Pieper, Carl; Vann, Richard D

2014-08-15

Hyperoxia during diving has been suggested to exacerbate hypercapnic narcosis and promote unconsciousness. We tested this hypothesis in male volunteers (12 at rest, 10 at 75 W cycle ergometer exercise) breathing each of four gases in a hyperbaric chamber. Inspired Po2 (PiO2 ) was 0.21 and 1.3 atmospheres (atm) without or with an individual subject's maximum tolerable inspired CO2 (PiO2 = 0.055-0.085 atm). Measurements included end-tidal CO2 partial pressure (PetCO2 ), rating of perceived discomfort (RPD), expired minute ventilation (V̇e), and cognitive function assessed by auditory n-back test. The most prominent finding was, irrespective of PetCO2 , that minute ventilation was 8-9 l/min greater for rest or exercise with a PiO2 of 1.3 atm compared with 0.21 atm (P < 0.0001). For hyperoxic gases, PetCO2 was consistently less than for normoxic gases (P < 0.01). For hyperoxic hypercapnic gases, n-back scores were higher than for normoxic gases (P < 0.01), and RPD was lower for exercise but not rest (P < 0.02). Subjects completed 66 hyperoxic hypercapnic trials without incident, but five stopped prematurely because of serious symptoms (tunnel vision, vision loss, dizziness, panic, exhaustion, or near syncope) during 69 normoxic hypercapnic trials (P = 0.0582). Serious symptoms during hypercapnic trials occurred only during normoxia. We conclude serious symptoms with hyperoxic hypercapnia were absent because of decreased PetCO2 consequent to increased ventilation. Copyright © 2014 the American Physiological Society.

Effects of chronic normobaric hypoxic and hypercapnic exposure in rats: Prevention of experimental chronic mountain sickness by hypercapnia

NASA Astrophysics Data System (ADS)

Lincoln, B.; Bonkovsky, H. L.; Ou, Lo-Chang

1987-09-01

A syndrome of experimental chronic mountain sickness can be produced in the Hilltop strain of Sprague-Dawley rats by chronic hypobaric hypoxic exposure. This syndrome is characterized by polycythemia, plasma hemoglobinemia, pulmonary hypertension and right ventricular hypertrophy with eventual failure and death. It has generally been assumed that these changes are caused by chronic hypoxemia, not by hypobaric exposure per se. We have now confirmed this directly by showing that chronic normobaric hypoxic exposure (10.5% O2) produces similar hematologic and hemodynamic changes. Further, the addition of hypercapnic exposure to the hypoxic exposure blunted or prevented the effects of the hypoxic exposure probably by stimulating respiration, thus increasing the rate of oxygen delivery to the cells. Changes in the rate-controlling enzymes of hepatic heme metabolism, 5-aminolevulinate synthase and heme oxygenase, and in cytochrome(s) P-450, the major hepatic hemoprotein(s), were also measured in hypoxic and hypercapnic rats. Hypoxia decreased 5-aminolevulinate synthase and increased cytochrome(s) P-450, probably by increasing the size of a “regulatory” heme pool within hepatocytes. These changes were also prevented by the addition of hypercapnic to hypoxic exposure.

Consequences of peripheral chemoreflex inhibition with low-dose dopamine in humans

PubMed Central

Niewinski, Piotr; Tubek, Stanislaw; Banasiak, Waldemar; Paton, Julian F R; Ponikowski, Piotr

2014-01-01

Low-dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double-blind, placebo-controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low-dose dopamine (2 μg kg–1 min–1) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function. PMID:24396060

West Nile Meningoencephalitis Presenting as Isolated Bulbar Palsy With Hypercapnic Respiratory Failure: Case Report and Literature Review.

PubMed

Tso, Geoffrey; Kaldas, Kirsten; Springer, Joseph; Barot, Nikhil; Kamangar, Nader

2016-05-01

Since the outbreak of West Nile virus (WNV) in the United States in 1999, the WNV neuroinvasive disease has been increasingly reported with a wide spectrum of neuromuscular manifestations. We submit a case of a 46-year-old male with a history of alcohol abuse, diabetes, hypertension, and hepatitis C who presented with fever, nausea, shortness of breath, and dysphagia. The patient rapidly developed hypercapnic respiratory failure and was found to have WNV meningoencephalitis without obvious neuromuscular weakness. His hospital course was significant for repeated failures of extubation secondary to persistent bulbar weakness eventually requiring tracheotomy. This is a unique case of WNV meningoencephalitis with bulbar palsy without other neuromuscular manifestations resulting in recurrent hypercapnic respiratory failure. © The Author(s) 2015.

The role of spinal cord transmission in the ventilatory response to electrically induced exercise in the anaesthetized dog

PubMed Central

Cross, Brenda A.; Davey, A.; Guz, A.; Katona, P. G.; Maclean, M.; Murphy, K.; Semple, S. J. G.; Stidwill, R.

1982-01-01

1. The ventilatory response to electrically induced `exercise' was studied in six chloralose-anaesthetized dogs. The on-transient and steady-state responses to `exercise' were compared in the same dogs before and after spinal cord transection at T8/9 (dermatome level T6/7) on fifteen occasions. 2. Phasic hind limb `exercise' was induced for periods of 4 min by passing current (2 Hz modulated 50 Hz sine wave) between two needles inserted through the hamstring muscles. The maximum current used was 30 mA. This was below the level previously found to produce an artifactual stimulation of breathing with the cord intact. 3. Cord transection produced no significant change in either the resting values of ventilation (˙VI) and CO2 production (˙VCO2) or the ventilatory equivalent for CO2 during `exercise' (△ ˙VI/ △ ˙VCO2). 4. During the steady state of exercise Pa, CO2 was on average significantly lower than at rest with the cord intact (mean △Pa, CO2, - 2·1 mmHg; range - 5·7 to + 1), and higher, though not significantly, with the cord cut (mean Pa, CO2, + 1·2 mmHg; range - 1·5 to + 4·3). However, even in the absence of spinal cord transmission, the ventilatory response to exercise could not be accounted for on the basis of CO2 sensitivity; the △ ˙VI/ △Pa,CO2 obtained with exercise (apparent sensitivity) was significantly greater than that obtained with CO2 inhalation (true sensitivity) both before and after cord section. 5. ˙VI and ˙VCO2 increased more slowly with the cord cut than with the cord intact. This was thought to be due to a slower increase in venous return in the absence of sympathetic innervation of the lower half of the body following cord transection. 6. Similar experiments were performed during muscle paralysis (following gallamine triethiodide). Ventilation was maintained with a respirator controlled by phrenic nerve activity. These experiments showed an increase in ventilation, independent of muscle contraction, which was only present when the cord was intact and which was confined to the on-transient. Only in the absence of spinal cord transmission could there be certainty that the dynamics of the ventilatory response to electrically induced `exercise' was free of artifact. 7. It was concluded that spinal cord transmission is not necessary for the steady-state ventilatory response to electrically induced exercise of the hind limbs. 8. The dog with spinal cord transection provides a suitable model for the study of the chemical control of breathing during electrically induced exercise. PMID:6292406

Phenotyping Pharyngeal Pathophysiology using Polysomnography in Patients with Obstructive Sleep Apnea.

PubMed

Sands, Scott A; Edwards, Bradley A; Terrill, Philip I; Taranto-Montemurro, Luigi; Azarbarzin, Ali; Marques, Melania; Hess, Lauren B; White, David P; Wellman, Andrew

2018-05-01

Therapies for obstructive sleep apnea (OSA) could be administered on the basis of a patient's own phenotypic causes ("traits") if a clinically applicable approach were available. Here we aimed to provide a means to quantify two key contributors to OSA-pharyngeal collapsibility and compensatory muscle responsiveness-that is applicable to diagnostic polysomnography. Based on physiological definitions, pharyngeal collapsibility determines the ventilation at normal (eupneic) ventilatory drive during sleep, and pharyngeal compensation determines the rise in ventilation accompanying a rising ventilatory drive. Thus, measuring ventilation and ventilatory drive (e.g., during spontaneous cyclic events) should reveal a patient's phenotypic traits without specialized intervention. We demonstrate this concept in patients with OSA (N = 29), using a novel automated noninvasive method to estimate ventilatory drive (polysomnographic method) and using "gold standard" ventilatory drive (intraesophageal diaphragm EMG) for comparison. Specialized physiological measurements using continuous positive airway pressure manipulation were employed for further comparison. The validity of nasal pressure as a ventilation surrogate was also tested (N = 11). Polysomnography-derived collapsibility and compensation estimates correlated favorably with those quantified using gold standard ventilatory drive (R = 0.83, P < 0.0001; and R = 0.76, P < 0.0001; respectively) and using continuous positive airway pressure manipulation (R = 0.67, P < 0.0001; and R = 0.64, P < 0.001; respectively). Polysomnographic estimates effectively stratified patients into high versus low subgroups (accuracy, 69-86% vs. ventilatory drive measures; P < 0.05). Traits were near-identical using nasal pressure versus pneumotach (N = 11, R ≥ 0.98, both traits; P < 0.001). Phenotypes of pharyngeal dysfunction in OSA are evident from spontaneous changes in ventilation and ventilatory drive during sleep, enabling noninvasive phenotyping in the clinic. Our approach may facilitate precision therapeutic interventions for OSA.

Sleep and Respiration in Microgravity

NASA Technical Reports Server (NTRS)

West, John B.; Elliott, Ann R.; Prisk, G. Kim; Paiva, Manuel

2003-01-01

Sleep is often reported to be of poor quality in microgravity, and studies on the ground have shown a strong relationship between sleep-disordered breathing and sleep disruption. During the 16-day Neurolab mission, we studied the influence of possible changes in respiratory function on sleep by performing comprehensive sleep recordings on the payload crew on four nights during the mission. In addition, we measured the changes in the ventilatory response to low oxygen and high carbon dioxide in the same subjects during the day, hypothesizing that changes in ventilatory control might affect respiration during sleep. Microgravity caused a large reduction in the ventilatory response to reduced oxygen. This is likely the result of an increase in blood pressure at the peripheral chemoreceptors in the neck that occurs when the normally present hydrostatic pressure gradient between the heart and upper body is abolished. This reduction was similar to that seen when the subjects were placed acutely in the supine position in one-G. In sharp contrast to low oxygen, the ventilatory response to elevated carbon dioxide was unaltered by microgravity or the supine position. Because of the similarities of the findings in microgravity and the supine position, it is unlikely that changes in ventilatory control alter respiration during sleep in microgravity. During sleep on the ground, there were a small number of apneas (cessation of breathing) and hypopneas (reduced breathing) in these normal subjects. During sleep in microgravity, there was a reduction in the number of apneas and hypopneas per hour compared to preflight. Obstructive apneas virtually disappeared in microgravity, suggesting that the removal of gravity prevents the collapse of upper airways during sleep. Arousals from sleep were reduced in microgravity compared to preflight, and virtually all of this reduction was as a result of a reduction in the number of arousals from apneas and hypopneas. We conclude that any sleep disruption in microgravity is not the result of respiratory factors.

Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation.

PubMed

Terzano, Claudio; Di Stefano, Fabio; Conti, Vittoria; Di Nicola, Marta; Paone, Gregorino; Petroianni, Angelo; Ricci, Alberto

2012-01-01

Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure. Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO(2) and PaCO(2) and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis-metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1 ± 9.8, 36.2 ± 8.9 and 53.3 ± 4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis-metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.

Mixed Acid-Base Disorders, Hydroelectrolyte Imbalance and Lactate Production in Hypercapnic Respiratory Failure: The Role of Noninvasive Ventilation

PubMed Central

Terzano, Claudio; Di Stefano, Fabio; Conti, Vittoria; Di Nicola, Marta; Paone, Gregorino; Petroianni, Angelo; Ricci, Alberto

2012-01-01

Background Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure. Methods Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO2 and PaCO2 and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. Results Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis–metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1±9.8, 36.2±8.9 and 53.3±4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis–metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. Conclusions Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated. PMID:22539963

Metabolic alkalosis contributes to acute hypercapnic respiratory failure in adult cystic fibrosis.

PubMed

Holland, Anne E; Wilson, John W; Kotsimbos, Thomas C; Naughton, Matthew T

2003-08-01

and study objectives: Patients with end-stage cystic fibrosis (CF) develop respiratory failure and hypercapnia. In contrast to COPD patients, altered electrolyte transport and malnutrition in CF patients may predispose them to metabolic alkalosis and, therefore, may contribute to hypercapnia. The aim of this study was to determine the prevalence of metabolic alkalosis in adults with hypercapnic respiratory failure in the setting of acute exacerbations of CF compared with COPD. Levels of arterial blood gases, plasma electrolytes, and serum albumin from 14 consecutive hypercapnic CF patients who had been admitted to the hospital with a respiratory exacerbation were compared with 49 consecutive hypercapnic patients with exacerbations of COPD. Hypercapnia was defined as a PaCO(2) of > or = 45 mm Hg. Despite similar PaCO(2) values, patients in the CF group were significantly more alkalotic than were those in the COPD group (mean [+/- SD] pH, 7.43 +/- 0.03 vs 7.37 +/- 0.05, respectively; p < 0.01). A mixed respiratory acidosis and metabolic alkalosis was evident in 71% of CF patients and 22% of COPD patients (p < 0.01). The mean concentrations of plasma chloride (95.1 +/- 4.9 vs 99.8 +/- 5.2 mmol/L, respectively; p < 0.01) and sodium (136.5 +/- 2.8 vs 140.4 +/- 4.5 mmol/L, respectively; p < 0.01) were significantly lower in the CF group, and the levels of serum albumin were significantly reduced (27.4 +/- 5.8 vs 33.7 +/- 4.8 mmol/L, respectively; p < 0.01). Metabolic alkalosis contributes to hypercapnic respiratory failure in adults with acute exacerbations of CF. This acid-base disturbance occurs in conjunction with reduced total body salt levels and hypoalbuminemia.

Effects of exercise position on the ventilatory responses to exercise in chronic heart failure.

PubMed

Armour, W; Clark, A L; McCann, G P; Hillis, W S

1998-09-01

Patients with heart failure frequently complain of orthopnoea. The objective was to assess the ventilatory response of patients with chronic heart failure during erect and supine exercise. Maximal incremental exercise testing with metabolic gas exchange measurements in erect and supine positions conducted in random order. Tertiary referral centre for cardiology. Nine patients with heart failure (aged 61.9+/-6.1 years) and 10 age matched controls (63.8+/-4.6). Metabolic gas exchange measurements. The slope of the relation between ventilation and carbon dioxide production. Ratings of perceived breathlessness during exercise. Oxygen consumption (VO2) and ventilation were higher during erect exercise at each stage in each group. Peak VO2 was [mean (SD)] 17.12 ml/kg/min (4.07) erect vs 12.92 (3.61) supine in the patients (P<0.01) and 22.62 (5.03) erect-supine vs 19.16 (3.78) erect (P<0.01) in the controls. Ratings of perceived exertion were higher in the patients at each stage, but unaffected by posture. There was no difference in the slope of the relation between ventilation and carbon dioxide production between erect and supine exercise 36.39 (6.12) erect vs 38.42 (8.89) supine for patients; 30.05 (4.52) vs 28.80 (3.96) for controls. In this group of patients during exercise, there was no change in the perception of breathlessness, nor the ventilatory response to carbon dioxide production with change in posture, although peak ventilation was greater in the erect position. The sensation of breathlessness may be related to the appropriateness of the ventilatory response to exertion rather than to the absolute ventilation.

Relationship between motor corticospinal excitability and ventilatory response during intense exercise.

PubMed

Yunoki, Takahiro; Matsuura, Ryouta; Yamanaka, Ryo; Afroundeh, Roghayyeh; Lian, Chang-Shun; Shirakawa, Kazuki; Ohtsuka, Yoshinori; Yano, Tokuo

2016-06-01

Effort sense has been suggested to be involved in the hyperventilatory response during intense exercise (IE). However, the mechanism by which effort sense induces an increase in ventilation during IE has not been fully elucidated. The aim of this study was to determine the relationship between effort-mediated ventilatory response and corticospinal excitability of lower limb muscle during IE. Eight subjects performed 3 min of cycling exercise at 75-85 % of maximum workload twice (IE1st and IE2nd). IE2nd was performed after 60 min of resting recovery following 45 min of submaximal cycling exercise at the workload corresponding to ventilatory threshold. Vastus lateralis muscle response to transcranial magnetic stimulation of the motor cortex (motor evoked potentials, MEPs), effort sense of legs (ESL, Borg 0-10 scale), and ventilatory response were measured during the two IEs. The slope of ventilation (l/min) against CO2 output (l/min) during IE2nd (28.0 ± 5.6) was significantly greater than that (25.1 ± 5.5) during IE1st. Mean ESL during IE was significantly higher in IE2nd (5.25 ± 0.89) than in IE1st (4.67 ± 0.62). Mean MEP (normalized to maximal M-wave) during IE was significantly lower in IE2nd (66 ± 22 %) than in IE1st (77 ± 24 %). The difference in mean ESL between the two IEs was significantly (p < 0.05, r = -0.82) correlated with the difference in mean MEP between the two IEs. The findings suggest that effort-mediated hyperventilatory response to IE may be associated with a decrease in corticospinal excitability of exercising muscle.

Model-based stability assessment of ventilatory control in overweight adolescents with obstructive sleep apnea during NREM sleep.

PubMed

Nava-Guerra, L; Tran, W H; Chalacheva, P; Loloyan, S; Joshi, B; Keens, T G; Nayak, K S; Davidson Ward, S L; Khoo, M C K

2016-07-01

Obstructive sleep apnea (OSA) involves the interplay of several different factors such as an unfavorable upper airway anatomy, deficiencies in pharyngeal muscle responsiveness, a low arousal threshold, and ventilatory control instability. Although the stability of ventilatory control has been extensively studied in adults, little is known about its characteristics in the pediatric population. In this study, we developed a novel experimental setup that allowed us to perturb the respiratory system during natural non-rapid eye movement (NREM) sleep conditions by manipulating the inspiratory pressure, provided by a bilevel pressure ventilator, to induce sighs after upper airway stabilization. Furthermore, we present a modeling framework that utilizes the noninvasively measured ventilatory responses to the induced sighs and spontaneous breathing data to obtain representations of the processes involved in the chemical regulation of respiration and extract their stability characteristics. After validation with simulated data, the modeling technique was applied to data collected experimentally from 11 OSA and 15 non-OSA overweight adolescents. Statistical analysis of the model-derived stability parameters revealed a significantly higher plant gain and lower controller gain in the OSA group (P = 0.046 and P = 0.007, respectively); however, no differences were found in loop gain (LG) and circulatory time delay between the groups. OSA severity and LG, within the 0.03-0.04-Hz frequency band, were significantly negatively associated (r = -0.434, P = 0.026). Contrary to what has been found in adults, our results suggest that in overweight adolescents, OSA is unlikely to be initiated through ventilatory instability resulting from elevated chemical loop gain. Copyright © 2016 the American Physiological Society.

Ventilatory responses to dynamic exercise elicited by intramuscular sensors

NASA Technical Reports Server (NTRS)

Smith, S. A.; Gallagher, K. M.; Norton, K. H.; Querry, R. G.; Welch-O'Connor, R. M.; Raven, P. B.

1999-01-01

PURPOSE: Eight subjects, aged 27.0+/-1.6 yr, performed incremental workload cycling to investigate the contribution of skeletal muscle mechano- and metaboreceptors to ventilatory control during dynamic exercise. METHODS: Each subject performed four bouts of exercise: exercise with no intervention (CON); exercise with bilateral thigh cuffs inflated to 90 mm Hg (CUFF); exercise with application of lower-body positive pressure (LBPP) to 45 torr (PP); and exercise with 90 mm Hg thigh cuff inflation and 45 torr LBPP (CUFF+PP). Ventilatory responses and pulmonary gas exchange variables were collected breath-by-breath with concomitant measurement of leg intramuscular pressure. RESULTS: Ventilation (VE) was significantly elevated from CON during PP and CUFF+PP at workloads corresponding to > or = 60% CON peak oxygen uptake (VO2peak) and during CUFF at workloads > or = 80% CON VO2peak, P < 0.05. The VO2 at which ventilatory threshold occurred was significantly reduced from CON (2.17+/-0.28 L x min(-1)) to 1.60+/-0.19 L x min(-1), 1.45+/-0.15 L x min(-1), and 1.15+/-0.11 L x min(-1) during CUFF, PP, and CUFF+PP, respectively. The slope of the linear regression describing the VE/CO2 output relationship was increased from CON by approximately 22% during CUFF, 40% during PP, and 41% during CUFF+PP. CONCLUSIONS: As intramuscular pressure was significantly elevated immediately upon application of LBPP during PP and CUFF+PP without a concomitant increase in VE, it seems unlikely that LBPP-induced increases in VE can be attributed to activation of the mechanoreflex. These findings suggest that LBPP-induced reductions in perfusion pressure and decreases in venous outflow resulting from inflation of bilateral thigh cuffs may generate a metabolite sensitive intramuscular ventilatory stimulus.

Noninvasive versus conventional ventilation to treat hypercapnic encephalopathy in chronic obstructive pulmonary disease.

PubMed

Scala, Raffaele; Nava, Stefano; Conti, Giorgio; Antonelli, Massimo; Naldi, Mario; Archinucci, Ivano; Coniglio, Giovanni; Hill, Nicholas S

2007-12-01

We recently reported a high success rate using noninvasive positive pressure ventilation (NPPV) to treat COPD exacerbations with hypercapnic encephalopathy. This study compared the hospital outcomes of NPPV vs. conventional mechanical ventilation (CMV) in COPD exacerbations with moderate to severe hypercapnic encephalopathy, defined by a Kelly score of 3 or higher. A 3-year prospective matched case-control study in a respiratory semi-intensive care unit (RSICU) and intensive care unit (ICU). From 103 consecutive patients the study included 20 undergoing NPPV and 20 CMV, matched for age, simplified acute physiology score II, and baseline arterial blood gases. ABG significantly improved in both groups after 2 h. The rate of complications was lower in the NPPV group than in the CMV group due to fewer cases of nosocomial pneumonia and sepsis. In-hospital mortality, 1-year mortality, and tracheostomy rates were similar in the two groups. Fewer patients remained on ventilation after 30 days in NPPV group. The NPPV group showed a shorter duration of ventilation. In COPD exacerbations with moderate to severe hypercapnic encephalopathy, the use of NPPV performed by an experienced team compared to CMV leads to similar short and long-term survivals with a reduced nosocomial infection rate and duration of ventilation.

Carotid body potentiation during chronic intermittent hypoxia: implication for hypertension

PubMed Central

Del Rio, Rodrigo; Moya, Esteban A.; Iturriaga, Rodrigo

2014-01-01

Autonomic dysfunction is involved in the development of hypertension in humans with obstructive sleep apnea, and animals exposed to chronic intermittent hypoxia (CIH). It has been proposed that a crucial step in the development of the hypertension is the potentiation of the carotid body (CB) chemosensory responses to hypoxia, but the temporal progression of the CB chemosensory, autonomic and hypertensive changes induced by CIH are not known. We tested the hypothesis that CB potentiation precedes the autonomic imbalance and the hypertension in rats exposed to CIH. Thus, we studied the changes in CB chemosensory and ventilatory responsiveness to hypoxia, the spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV) and arterial blood pressure in pentobarbital anesthetized rats exposed to CIH for 7, 14, and 21 days. After 7 days of CIH, CB chemosensory and ventilatory responses to hypoxia were enhanced, while BRS was significantly reduced by 2-fold in CIH-rats compared to sham-rats. These alterations persisted until 21 days of CIH. After 14 days, CIH shifted the HRV power spectra suggesting a predominance of sympathetic over parasympathetic tone. In contrast, hypertension was found after 21 days of CIH. Concomitant changes between the gain of spectral HRV, BRS, and ventilatory hypoxic chemoreflex showed that the CIH-induced BRS attenuation preceded the HRV changes. CIH induced a simultaneous decrease of the BRS gain along with an increase of the hypoxic ventilatory gain. Present results show that CIH-induced persistent hypertension was preceded by early changes in CB chemosensory control of cardiorespiratory and autonomic function. PMID:25429271

Pathogenesis of Central and Complex Sleep Apnoea

PubMed Central

Orr, Jeremy E.; Malhotra, Atul; Sands, Scott A.

2016-01-01

Central sleep apnoea (CSA)—the temporary absence or diminution of ventilator effort during sleep—is seen in a variety of forms including periodic breathing in infancy and healthy adults at altitude and Cheyne-Stokes respiration in heart failure. In most circumstances, the cyclic absence of effort is paradoxically a consequence of hypersensitive ventilatory chemoreflex responses to oppose changes in airflow, i.e. elevated loop gain, leading to overshoot/undershoot ventilatory oscillations. Considerable evidence illustrates overlap between CSA and obstructive sleep apnoea (OSA), including elevated loop gain in patients with OSA and the presence of pharyngeal narrowing during central apnoeas. Indeed, treatment of OSA, whether via CPAP, tracheostomy, or oral appliances, can reveal CSA, an occurrence referred to as complex sleep apnoea. Factors influencing loop gain include increased chemosensitivity (increased controller gain), reduced damping of blood gas levels (increased plant gain) and increased lung to chemoreceptor circulatory delay. Sleep-wake transitions and pharyngeal dilator muscle responses effectively raise the controller gain and therefore also contribute to total loop gain and overall instability. In some circumstances, for example apnoea of infancy and central congenital hypoventilation syndrome, central apnoeas are the consequence of ventilatory depression and defective ventilatory responses, i.e. low loop gain. The efficacy of available treatments for CSA can be explained in terms of their effects on loop gain, e.g. CPAP improves lung volume (plant gain), stimulants reduce the alveolar-inspired PCO2 difference, supplemental oxygen lowers chemosensitivity. Understanding the magnitude of loop gain and the mechanisms contributing to instability may facilitate personalised interventions for CSA. PMID:27797160

Factors affecting the response to exercise in patients with severe pulmonary arterial hypertension.

PubMed

Flox-Camacho, Angela; Escribano-Subías, Pilar; Jiménez-López Guarch, Carmen; Fernández-Vaquero, Almudena; Martín-Ríos, Dolores; de la Calzada-Campo, Carlos Sáenz

2011-01-01

Ergospirometry objectively quantifies exercise capacity. Up until now, the response to exercise evaluated by ergospirometry in patients with pulmonary arterial hypertension has only been described in recently diagnosed.patients. Our aim is to describe the response to exercise in patients with severe pulmonary arterial hypertension under specific treatment and define which parameters determine their exercise capacity. A cross-sectional study was performed on 80 patients, 57 women, aged 45 (14), with severe pulmonary arterial hypertension (48 idiopathic, 14 related to toxic rapeseed oil, 13 to connective tissue disease, 5 to human immunodeficiency virus), mean pulmonary pressure at diagnosis 61(15)mmHg and after 49(33) months under treatment since diagnosis. Biomarkers were measured and echocardiography and ergospirometry were performed the same day. Our patients, under specific treatment, showed the typical behaviour of patients with pulmonary arterial hypertension with less limitation of both aerobic capacity and ventilatory efficiency. Being male (p=0.004), high ventilatory equivalent for carbon dioxide at anaerobic threshold (p<0.001) or biomarkers (p=0.006) were the strongest predictors of impaired peak oxygen uptake in multivariate analysis, whereas for an impaired percentage achieved of predicted value were right ventricle diastolic diameter (p<0.001), months of treatment (p=0.01) and high ventilatory equivalent for CO(2) (p<0.001). In pulmonary arterial hypertension, right ventricle dysfunction (expressed by its dilation or high NTproBNP) and impaired ventilatory inefficiency as well as being male or a short time under treatment can be considered as determining factors of impaired exercise capacity. Copyright © 2010 SEPAR. Published by Elsevier Espana. All rights reserved.

REAL-TIME MONITORING FOR TOXICITY CAUSED BY ...

EPA Pesticide Factsheets

This project, sponsored by EPA's Environmental Monitoring for Public Access and Community Tracking (EMPACT) program, evaluated the ability of an automated biological monitoring system that measures fish ventilatory responses (ventilatory rate, ventilatory depth, and cough rate) to detect developing toxic conditions in water.In laboratory tests, acutely toxic levels of both brevetoxin (PbTx-2) and toxic Pfiesteria piscicida cultures caused fish responses primarily through large increases in cough rate. In the field, the automated biomonitoring system operated continuously for 3 months on the Chicamacomico River, a tributary to the Chesapeake Bay that has had a history of intermittent toxic algal blooms. Data gathered through this effort complemented chemical monitoring data collected by the Maryland Department of Natural Resources (DNR) as part of their Pfiesteria monitoring program. After evaluation by DNR personnel, the public could access the data on the DNR Internet web site at www.dnr.state.md.us/bay/pfiesteria/00results.html or receive more detailed information at www.aquaticpath.umd.edu/empact.. The field biomonitor identified five fish response events. Increased conductivity combined with a substantial decrease in water temperature was the likely cause of one event, while contaminants (probably surfactants) released from inadequately rinsed particle filters produced another response. The other three events, characterized by greatly increased cough ra

Effect of upper airway CO2 pattern on ventilatory frequency in tegu lizards.

PubMed

Ballam, G O; Coates, E L

1989-07-01

Nasal CO2-sensitive receptors are reported to depress ventilatory frequency in several reptilian species in response to constant low levels of inspired CO2. The purpose of this study was to determine the influence of phasic patterns of CO2 in the upper airways on ventilation. Awake lizards (Tupinambis nigropunctatus) breathed through an endotracheal tube from an isolated gas source. A second gas mixture was forced at constant flow into the external nares. A concentration of 4% CO2 was intermittently pulsed through the nares in a square-wave pattern with a frequency of 60, 12, 6, 4.2, 1.8, and 0.6 cycles/min. Concentrations of 2, 3, 4, and 6% CO2 were also pulsed through the nares at 12 cycles/min and compared with sustained levels of 1, 1.5, 2, and 3%. Additionally, 0 or 3% CO2 was forced through the upper airways with a servo system designed to mimic normal ventilatory flow and gas concentrations. No changes in breathing pattern were noted during any of the pulsing protocols, although a significant breathing frequency depression was present with sustained levels of CO2 of comparable mean concentrations. We conclude that ventilatory control is selectively responsive to sustained levels of environmental CO2 but not to phasic changes in upper airway CO2 concentration.

Comparison of the effects of moderate and severe hypercapnic acidosis on ventilation-induced lung injury.

PubMed

Yang, Wanchao; Yue, Ziyong; Cui, Xiaoguang; Guo, Yueping; Zhang, Lili; Zhou, Huacheng; Li, Wenzhi

2015-04-30

We have proved that hypercapnic acidosis (a PaCO2 of 80-100 mmHg) protects against ventilator-induced lung injury in rats. However, there remains uncertainty regarding the appropriate target PaCO2 or if greater CO2 "doses" (PaCO2 > 100 mmHg) demonstrate this effect. We wished to determine whether severe acute hypercapnic acidosis can reduce stretch-induced injury, as well as the role of nuclear factor-κB (NF-κB) in the effects of acute hypercapnic acidosis. Fifty-four rats were ventilated for 4 hours with a pressure-controlled ventilation mode set at a peak inspiratory pressure (PIP) of 30 cmH2O. A gas mixture of carbon dioxide with oxygen (FiCO2 = 4-5%, FiCO2 = 11-12% or FiCO2 = 16-17%; FiO2 = 0.7; balance N2) was immediately administered to maintain the target PaCO2 in the NC (a PaCO2 of 35-45 mmHg), MHA (a PaCO2 of 80-100 mmHg) and SHA (a PaCO2 of 130-150 mmHg) groups. Nine normal or non-ventilated rats served as controls. The hemodynamics, gas exchange and inflammatory parameters were measured. The role of NF-κB pathway in hypercapnic acidosis-mediated protection from high-pressure stretch injury was then determined. In the NC group, high-pressure ventilation resulted in a decrease in PaO2/FiO2 from 415.6 (37.1) mmHg to 179.1 (23.5) mmHg (p < 0.001), but improved by MHA (379.9 ± 34.5 mmHg) and SHA (298.6 ± 35.3 mmHg). The lung injury score in the SHA group (7.8 ± 1.6) was lower than the NC group (11.8 ± 2.3, P < 0.05) but was higher than the MHA group (4.4 ± 1.3, P < 0.05). Compared with the NC group, after 4 h of high pressure ventilation, the MHA and SHA groups had decreases in MPO activity of 67% and 33%, respectively, and also declined the levels of TNF-α (58% versus 72%) and MIP-2 (76% versus 60%) in the BALF. Additionally, both hypercapnic acidosis groups reduced stretch-induced NF-κB activation (p < 0.05) and significantly decreased lung ICAM-1 expression (p < 0.05). Moderate hypercapnic acidosis (PaCO2 maintained at 80-100 mmHg) has a greater protective effect on high-pressure ventilation-induced inflammatory injury. The potential mechanisms may involve alterations in NF-κB activity.

Substance P Differentially Modulates Firing Rate of Solitary Complex (SC) Neurons from Control and Chronic Hypoxia-Adapted Adult Rats

PubMed Central

Nichols, Nicole L.; Powell, Frank L.; Dean, Jay B.; Putnam, Robert W.

2014-01-01

NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats. PMID:24516602

Effects of fenoterol on ventilatory response to hypercapnia and hypoxia in patients with chronic obstructive pulmonary disease

PubMed Central

Suzuki, S.; Watanuki, Y.; Yoshiike, Y.; Okubo, T.

1997-01-01

BACKGROUND: It has previously been shown that fenoterol, a beta 2 adrenergic agonist, increases the ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) in normal subjects. The effects of beta 2 adrenergic agonists on chemoreceptors in patients with chronic obstructive pulmonary disease (COPD) remain controversial. This study was designed to examine whether fenoterol increases the HVR and HCVR in patients with COPD. METHODS: The HCVR was tested in 20 patients using a rebreathing method and the HVR was examined using a progressive isocapnic hypoxic method. The HCVR and HVR were assessed by calculating the slopes of plots of occlusion pressure (P0.1) and ventilation (VE) against end tidal carbon dioxide pressure (PETCO2) and arterial oxygen saturation (SaO2), respectively. Spirometric values, lung volumes, and respiratory muscle strength were also measured. The HCVR and HVR were examined after the oral administration of fenoterol (15 mg/day) or placebo for seven days. RESULTS: Fenoterol treatment increased the forced expiratory volume in one second (FEV1) and inspiratory muscle strength. In the HCVR the slope of P0.1 versus PETCO2 was increased by fenoterol from 0.35 (0.23) to 0.43 (0.24) (p < 0.01). Moreover, the P0.1 at PETCO2 of 8 kPa was higher on fenoterol than on placebo (p < 0.05) and the VE was also greater (p < 0.01). In the HVR fenoterol treatment increased the P0.1 at 80% SaO2 from 0.90 (0.72) to 0.97 (0.55) kPa (p < 0.05) while the slopes of the response of P0.1 and VE were not changed. CONCLUSIONS: Fenoterol increases the ventilatory response to hypercapnia in patients with COPD, presumably by stimulation of the central chemoreceptor. The hypoxic ventilatory response is only slightly affected by fenoterol. 


 PMID:9059471

Impaired ventilatory acclimatization to hypoxia in female mice overexpressing erythropoietin: unexpected deleterious effect of estradiol in carotid bodies.

PubMed

Gassmann, Max; Pfistner, Christine; Doan, Van Diep; Vogel, Johannes; Soliz, Jorge

2010-12-01

Apart from enhancing the production of red blood cells, erythropoietin (Epo) alters the ventilatory response when oxygen supply is reduced. We recently demonstrated that Epo's beneficial effect on the ventilatory response to acute hypoxia is sex dependent, with female mice being better able to cope with reduced oxygenation. In the present work, we hypothesized that ventilatory acclimatization to chronic hypoxia (VAH) in transgenic female mice (Tg6) harboring high levels of Epo in the brain and blood will also be improved compared with wild-type (WT) animals. Surprisingly, VAH was blunted in Tg6 female mice. To define whether this phenomenon had a central (brain stem respiratory centers) and/or peripheral (carotid bodies) origin, a bilateral transection of carotid sinus nerve (chemodenervation) was performed. This procedure allowed the analysis of the central response in the absence of carotid body information. Interestingly, chemodenervation restored the VAH in Tg6 mice, suggesting that carotid bodies were responsible for the blunted response. Coherently with this observation, the sensitivity to oxygen alteration in arterial blood (Dejour test) after chronic hypoxia was lower in transgenic carotid bodies compared with the WT control. As blunted VAH occurred in female but not male transgenic mice, the involvement of sex female steroids was obvious. Indeed, measurement of sexual female hormones revealed that the estradiol serum level was 4 times higher in transgenic mice Tg6 than in WT animals. While ovariectomy decreased VAH in WT females, this treatment restored VAH in Tg6 female mice. In line with this observation, injections of estradiol in ovariectomized Tg6 females dramatically reduced the VAH. We concluded that during chronic hypoxia, estradiol in carotid bodies suppresses the Epo-mediated elevation of ventilation. Considering the increased application of recombinant Epo for a variety of disorders, our data imply the need to take the patient's hormonal status into consideration.

Sinusoidal high-intensity exercise does not elicit ventilatory limitation in chronic obstructive pulmonary disease.

PubMed

Porszasz, Janos; Rambod, Mehdi; van der Vaart, Hester; Rossiter, Harry B; Ma, Shuyi; Kiledjian, Rafi; Casaburi, Richard

2013-06-01

During exercise at critical power (CP) in chronic obstructive pulmonary disease (COPD) patients, ventilation approaches its maximum. As a result of the slow ventilatory dynamics in COPD, ventilatory limitation during supramaximal exercise might be escaped using rapid sinusoidal forcing. Nine COPD patients [age, 60.2 ± 6.9 years; forced expiratory volume in the first second (FEV(1)), 42 ± 17% of predicted; and FEV(1)/FVC, 39 ± 12%] underwent an incremental cycle ergometer test and then four constant work rate cycle ergometer tests; tolerable duration (t(lim)) was recorded. Critical power was determined from constant work rate testing by linear regression of work rate versus 1/t(lim). Patients then completed fast (FS; 60 s period) and slow (SS; 360 s period) sinusoidally fluctuating exercise tests with mean work rate at CP and peak at 120% of peak incremental test work rate, and one additional test at CP; each for a 20 min target. The value of t(lim) did not differ between CP (19.8 ± 0.6 min) and FS (19.0 ± 2.5 min), but was shorter in SS (13.2 ± 4.2 min; P < 0.05). The sinusoidal ventilatory amplitude was minimal (37.4 ± 34.9 ml min(-1) W(-1)) during FS but much larger during SS (189.6 ± 120.4 ml min(-1) W(-1)). The total ventilatory response in SS reached 110 ± 8.0% of the incremental test peak, suggesting ventilatory limitation. Slow components in ventilation during constant work rate and FS exercises were detected in most subjects and contributed appreciably to the total response asymptote. The SS exercise was associated with higher mid-exercise lactate concentrations (5.2 ± 1.7, 7.6 ± 1.7 and 4.5 ± 1.3 mmol l(-1) in FS, SS and CP). Large-amplitude, rapid sinusoidal fluctuation in work rate yields little fluctuation in ventilation despite reaching 120% of the incremental test peak work rate. This high-intensity exercise strategy might be suitable for programmes of rehabilitative exercise training in COPD.

Pharmacodynamic effect of morphine-6-glucuronide versus morphine on hypoxic and hypercapnic breathing in healthy volunteers.

PubMed

Romberg, Raymonda; Olofsen, Erik; Sarton, Elise; Teppema, Luc; Dahan, Albert

2003-10-01

Morphine-6-glucuronide (M6G) is an active metabolite of morphine that is generally associated with less respiratory depression than morphine. Because M6G will be on the market in the near future, the authors assessed the time profile and relative potency of M6G's effect versus morphine's effect on carbon dioxide-driven and hypoxic breathing. In nine healthy female volunteers, the effects of 0.2 mg/kg intravenous M6G, 0.13 mg/kg intravenous morphine, and intravenous placebo were tested on ventilation at a fixed end-tidal pressure of carbon dioxide (Petco2) of 45 mmHg (Vi45) and on the acute hypoxic ventilatory response (AHR). All subjects participated in all three arms of the study. Respiratory studies were performed at 1-h intervals for 7 h after drug infusion. The data were analyzed using a population dose-driven approach, which uses a dose rate in function of time as input function driving the pharmacodynamics, and a population pharmacokinetic-pharmacodynamic (PK/PD) approach in which fixed pharmacokinetic parameter values from the literature were used as input function to the respiratory model. From the latter analysis, the authors obtained the blood effect-site equilibration half-life (t1/2ke0) and the effect-site concentration producing 25% depression of Vi45 and AHR (C25). Values reported are mean +/- SE. Placebo had no effect on Vi45 or AHR over time. Both analysis approaches yielded good descriptions of the data with comparable model parameters. M6G PK/PD model parameters for Vi45 were t1/2ke0 2.1 +/- 0.2 h and C25 528 +/- 88 nm and for AHR were t1/2ke0 1.0 +/- 0.1 h and C25 873 +/- 81 nm. Morphine PK/PD model parameters for Vi45 were t1/2ke0 3.8 +/- 0.9 h and C25 28 +/- 6 nm and for AHR were t1/2ke0 4.3 +/- 0.6 h and C25 16 +/- 2 nm. Morphine is more potent in affecting hypoxic ventilatory control than M6G, with a potency ratio ranging from 1:19 for Vi45 to 1:50 for AHR. At drug concentrations causing 25% depression of Vi45, M6G caused only 15% depression of AHR, whereas morphine caused greater than 50% depression of AHR. Furthermore, the speed of onset/offset of M6G is faster than morphine by a factor of approximately 2. The authors discuss some of the possible mechanisms for the observed differences in opioid behavior.

Real-Time Cameraless Measurement System Based on Bioelectrical Ventilatory Signals to Evaluate Fear and Anxiety.

PubMed

Soh, Zu; Matsuno, Motoki; Yoshida, Masayuki; Tsuji, Toshio

2018-04-01

Fear and anxiety in fish are generally evaluated by video-based behavioral analysis. However, it is difficult to distinguish the psychological state of fish exclusively through video analysis, particularly whether the fish are freezing, which represents typical fear behavior, or merely resting. We propose a system that can measure bioelectrical signals called ventilatory signals and simultaneously analyze swimming behavior in real time. Experimental results comparing the behavioral analysis of the proposed system and the camera system showed a low error level with an average absolute position error of 9.75 ± 3.12 mm (about one-third of the body length) and a correlation between swimming speeds of r = 0.93 ± 0.07 (p < 0.01). We also exposed the fish to zebrafish skin extracts containing alarm substances that induce fear and anxiety responses to evaluate their emotional changes. The results confirmed that this solution significantly changed all behavioral and ventilatory signal indices obtained by the proposed system (p < 0.01). By combining the behavioral and ventilatory signal indices, we could detect fear and anxiety with a discrimination rate of 83.3% ± 16.7%. Furthermore, we found that the decreasing fear and anxiety over time could be detected according to the peak frequency of the ventilatory signals, which cannot be measured through video analysis.

Hypercapnic respiratory acidosis: a protective or harmful strategy for critically ill newborn foals?

PubMed

Vengust, Modest

2012-10-01

This paper reviews both the beneficial and adverse effects of permissive hypercapnic respiratory acidosis in critically ill newborn foals. It has been shown that partial carbon dioxide pressure (PCO2) above the traditional safe range (hypercapnia), has beneficial effects on the physiology of the respiratory, cardiovascular, and nervous system in neonates. In human neonatal critical care medicine permissive hypercapnic acidosis is generally well-tolerated by patients and is more beneficial to their wellbeing than normal carbon dioxide (CO2) pressure or normocapnia. Even though adverse effects of hypercapnia have been reported, especially in patients with central nervous system pathology and/or chronic infection, critical care clinicians often artificially increase PCO2 to take advantage of its positive effects on compromised neonate tissues. This is referred to as therapeutic hypercapnia. Hypercapnic respiratory acidosis is common in critically ill newborn foals and has traditionally been considered as not beneficial. A search of online scientific databases was conducted to survey the literature on the effects of hypercapnia in neonates, with emphasis on newborn foals. The dynamic status of safety levels of PCO2 and data on the effectiveness of different carbon dioxide levels are not available for newborn foals and should be scientifically determined. Presently, permissive hypercapnia should be implemented or tolerated cautiously in compromised newborn foals and its use should be based on relevant data from adult horses and other species.

The cerebrovascular response to carbon dioxide in humans

PubMed Central

Battisti-Charbonney, A; Fisher, J; Duffin, J

2011-01-01

Abstract Carbon dioxide (CO2) increases cerebral blood flow and arterial blood pressure. Cerebral blood flow increases not only due to the vasodilating effect of CO2 but also because of the increased perfusion pressure after autoregulation is exhausted. Our objective was to measure the responses of both middle cerebral artery velocity (MCAv) and mean arterial blood pressure (MAP) to CO2 in human subjects using Duffin-type isoxic rebreathing tests. Comparisons of isoxic hyperoxic with isoxic hypoxic tests enabled the effect of oxygen tension to be determined. During rebreathing the MCAv response to CO2 was sigmoidal below a discernible threshold CO2 tension, increasing from a hypocapnic minimum to a hypercapnic maximum. In most subjects this threshold corresponded with the CO2 tension at which MAP began to increase. Above this threshold both MCAv and MAP increased linearly with CO2 tension. The sigmoidal MCAv response was centred at a CO2 tension close to normal resting values (overall mean 36 mmHg). While hypoxia increased the hypercapnic maximum percentage increase in MCAv with CO2 (overall means from 76.5 to 108%) it did not affect other sigmoid parameters. Hypoxia also did not alter the supra-threshold MCAv and MAP responses to CO2 (overall mean slopes 5.5% mmHg-1 and 2.1 mmHg mmHg−1, respectively), but did reduce the threshold (overall means from 51.5 to 46.8 mmHg). We concluded that in the MCAv response range below the threshold for the increase of MAP with CO2, the MCAv measurement reflects vascular reactivity to CO2 alone at a constant MAP. PMID:21521758

High Mid-Flow to Vital Capacity Ratio and the Response to Exercise in Children With Congenital Heart Disease.

PubMed

Vilozni, Daphna; Alcaneses-Ofek, Maria Rosario; Reuveny, Ronen; Rosenblum, Omer; Inbar, Omri; Katz, Uriel; Ziv-Baran, Tomer; Dubnov-Raz, Gal

2016-12-01

Pulmonary mechanics may play a role in exercise intolerance in patients with congenital heart disease (CHD). A reduced FVC volume could increase the ratio between mid-flow (FEF 25-75% ) and FVC, which is termed high dysanapsis. The relationship between high dysanapsis and the response to maximum-intensity exercise in children with CHD had not yet been studied. The aim of this work was to examine whether high dysanapsis is related to the cardiopulmonary response to maximum-intensity exercise in pediatric subjects with CHD. We retrospectively collected data from 42 children and adolescents with CHD who had either high dysanapsis (ratio >1.2; n = 21) or normal dysanapsis (control) (n = 21) as measured by spirometry. Data extracted from cardiopulmonary exercise test reports included peak values of heart rate, work load, V̇ O 2 , V̇ CO 2 , and ventilation parameters and submaximum values, including ventilatory threshold and ventilatory equivalents. There were no significant differences in demographic and clinical parameters between the groups. Participants with high dysanapsis differed from controls in lower median peak oxygen consumption (65.8% vs 83.0% of predicted, P = .02), peak oxygen pulse (78.6% vs 87.8% of predicted, P = .02), ventilatory threshold (73.8% vs 85.3% of predicted, P = .03), and maximum breathing frequency (106% vs 121% of predicted, P = .035). In the high dysanapsis group only, median peak ventilation and tidal volume were significantly lower than 80% of predicted values. In children and adolescents with corrected CHD, high dysanapsis was associated with a lower ventilatory capacity and reduced aerobic fitness, which may indicate respiratory muscle impairments. Copyright © 2016 by Daedalus Enterprises.

[Pathophysiology of respiratory muscle weakness].

PubMed

Windisch, W

2008-03-01

The respiratory system consists of two parts which can be impaired independently from each other, the lungs and the respiratory pump. The latter is a complex system covering different anatomic structures: the breathing centre, the peripheral nervous system, the respiratory muscles, and the thorax. According to this complexity several underlying conditions can cause insufficiency of the respiratory pump, i. e. ventilatory failure. Disturbances of the breathing centre, different neuromuscular disorders, impairments of the mechanics, such as thoracic deformities or hyperinflation, and airway obstruction are example conditions responsible for ventilatory failure. Main characteristic of ventilatory failure is the occurrence of hypercapnia which is in contrast to pulmonary failure where diffusion disturbances typically not cause hypercapnia. Both acute and chronic ventilatory failure presenting with hypercapnia can develop. In acute ventilatory failure respiratory acidosis develops, but in chronic respiratory failure pH is normalized as a consequence of metabolic retention of bicarbonate. However, acute on chronic ventilatory failure can present with a combined picture, i. e. elevated bicarbonate levels, acidosis, and often severe hypercapnia. Clinical signs such as tachypnea, features of the underlying disease or hypercapnia are important diagnostic tools in addition to the measurement of pressures generated by the respiratory muscles. Non-invasive and widely available techniques, such as the assessment of the maximal ins- and expiratory mouth pressures (PImax, PEmax), should be used as screening instruments, but the reliability of these measurements is reduced due to the volitional character of the tests and due to the impossibility to define normal values. Inspiratory pressures can be assessed more accurately and independently from the patients' effort: with or without the insertion of oesophageal and gastric balloon catheters. However, this technique is more invasive and very complex. It is therefore restricted to centres with scientific aims.

Controlled atmosphere stunning of broiler chickens. I. Effects on behaviour, physiology and meat quality in a pilot scale system at a processing plant.

PubMed

Abeyesinghe, S M; McKeegan, D E F; McLeman, M A; Lowe, J C; Demmers, T G M; White, R P; Kranen, R W; van Bemmel, H; Lankhaar, J A C; Wathes, C M

2007-08-01

1. The effects of controlled atmosphere stunning on the behaviour, physiology and carcase and meat quality of broiler chickens were studied experimentally in a pilot scale plant. 2. Gas mixtures tested were: single phase anoxic mixture (90% Ar in air, <2% O(2)); single phase hypercapnic anoxic mixture (60% Ar, 30% CO(2) in air, <2% O(2)); and biphasic hypercapnic hyperoxygenation mixture (anaesthetic phase, 40% CO(2), 30% O(2), 30% N(2); euthanasia phase, 80% CO(2), 5% O(2), 15% N(2)). 3. Anoxic stunning resulted in the least respiratory disruption, mandibulation and motionlessness, but most head shaking, leg paddling and twitching. Loss of posture occurred soonest with hypercapnic anoxia with the earliest and most twitching and wing flapping in individuals and earliest leg paddling. Biphasic birds were most alert, exhibited most respiratory disruption and mandibulation, and had the latest loss of posture and fewest, but longest bouts of wing flapping and least leg paddling and twitching. 4. Significant and sudden bradycardia and arrhythmia were evident with all gas mixtures and were not related solely to anoxia or hypercapnia. Birds stunned by Ar anoxia showed a slightly more gradual decline from baseline rates, compared with hypercapnic mixtures. 5. Few differences were found between gas mixes in terms of carcase and meat quality. Initial bleeding rate was slowest in biphasic-stunned birds, but total blood loss was not affected. Acceleration of post-mortem metabolism in anoxic-stunned birds was not sufficient to allow de-boning within 5 h without the risk of tough meat. 6. On welfare grounds and taking into account other laboratory and field studies, a biphasic method (using consecutive phases of anaesthesia and euthanasia) of controlled atmosphere stunning of broilers is potentially more humane than anoxic or hypercapnic anoxic methods using argon or nitrogen.

Voluntary respiratory control and cerebral blood flow velocity upon ice-water immersion.

PubMed

Mantoni, Teit; Rasmussen, Jakob Højlund; Belhage, Bo; Pott, Frank Christian

2008-08-01

In non-habituated subjects, cold-shock response to cold-water immersion causes rapid reduction in cerebral blood flow velocity (approximately 50%) due to hyperventilation, increasing risk of syncope, aspiration, and drowning. Adaptation to the response is possible, but requires several cold immersions. This study examines whether thorough instruction enables non-habituated persons to attenuate the ventilatory component of cold-shock response. There were nine volunteers (four women) who were lowered into a 0 degrees C immersion tank for 60 s. Middle cerebral artery mean velocity (CBFV) was measured together with ventilatory parameters and heart rate before, during, and after immersion. Within seconds after immersion in ice-water, heart rate increased significantly from 95 +/- 8 to 126 +/- 7 bpm (mean +/- SEM). Immersion was associated with an elevation in respiratory rate (from 12 +/- 3 to 21 +/- 5 breaths, min(-1)) and tidal volume (1022 +/- 142 to 1992 +/- 253 ml). Though end-tidal carbon dioxide tension decreased from 4.9 +/- 0.13 to 3.9 +/- 0.21 kPa, CBFV was insignificantly reduced by 7 +/- 4% during immersion with a brief nadir of 21 +/- 4%. Even without prior cold-water experience, subjects were able to suppress reflex hyperventilation following ice-water immersion, maintaining the cerebral blood flow velocity at a level not associated with impaired consciousness. This study implies that those susceptible to accidental cold-water immersion could benefit from education in cold-shock response and the possibility of reducing the ventilatory response voluntarily.

From the Cover: Prenatal Nicotinic Exposure Attenuates Respiratory Chemoreflexes Associated With Downregulation of Tyrosine Hydroxylase and Neurokinin 1 Receptor in Rat Pup Carotid Body.

PubMed

Zhao, Lei; Zhuang, Jianguo; Gao, Xiuping; Ye, Chunyan; Lee, Lu-Yuan; Xu, Fadi

2016-09-01

Maternal cigarette smoke is the major risk of sudden infant death syndrome (SIDS). A depressed ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) is thought to be responsible for the pathogenesis of SIDS and the carotid body is critically involved in these responses. We have recently reported that prenatal nicotinic exposure (PNE) over the full gestation induces depressed HVR in rat pups. Here, we asked whether PNE (1) depressed not only HVR but also HCVR that were dependent on the carotid body, (2) affected some important receptors and neurochemicals expressed in the carotid body, such as tyrosine hydroxylase (TH), neurokinin-1 receptor (NK1R), and α7 nicotinic acetylcholine receptor (α7nAChR), and (3) blunted the ventilatory responses to activation of these receptors. To this end, HVR and HCVR in Ctrl and PNE pups were measured with plethysmography before and after carotid body ablation (Series I), mRNA expression and/or immunoreactivity (IR) of TH, NK1R, and α7nAChR in the carotid body were examined by RT-PCR and immunohistochemistry (Series II), and the ventilatory responses were tested before and after intracarotid injection of substance P (NK1R agonist) and AR-R17779 (α7nAChR agonist) (Series III). Our results showed that PNE (1) significantly depressed both HVR and HCVR and these depressions were abolished by carotid body ablation, (2) reduced the relative population of glomus cells, mRNA NK1R, and α7nAChR and IR of NK1R and TH in the carotid body, and (3) decreased ventilatory responses to intracarotid injection of substance P or AR-R17779. These results suggest that PNE acting via the carotid body could strikingly blunt HVR and HCVR, likely through downregulating TH and NK1R. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Changes in respiratory control after three hours of isocapnic hypoxia in humans

PubMed Central

Mahamed, Safraaz; Cunningham, David A; Duffin, James

2003-01-01

Despite the obvious role of hypoxia in eliciting respiratory acclimatisation in humans, the function of the peripheral chemoreflex is uncertain. We investigated this uncertainty using 3 h of isocapnic hypoxia as a stimulus (end-tidal PCO2, 0.5–1.0 mmHg above eucapnia; end-tidal PO2, 50 mmHg), hypothesising that this stimulus would induce an enhancement of the peripheral chemoreflex ventilatory response to hypoxia. Current evidence conflicts as to whether this enhancement is mediated by an increase in the sensitivity or a decrease in the threshold of the peripheral chemoreflex ventilatory response to carbon dioxide. Employing a modified rebreathing technique to assess chemoreflex function, we found evidence of the latter in nine healthy volunteers (six male, three female). Testing consisted of pairs of isoxic rebreathing tests at high and low levels of oxygen, performed before, immediately after and 1 h after a 3 h isocapnic hypoxic exposure. No parameters changed significantly in the high-oxygen rebreathing tests. In the low-oxygen rebreathing tests there were no changes in non-chemoreflex ventilatory drives, or in the sensitivity to carbon dioxide, but the carbon dioxide response threshold decreased (≈1.5 mmHg) immediately after exposure, and the decrease persisted for 1 h (one-way repeated-measures ANOVA; P < 0.05). We repeated the protocol in five of the original nine volunteers, but this time exposing them to isocapnic normoxia. No trends or significant changes were observed in any of the rebreathing test parameters. These findings demonstrate that in the earliest stages of acclimatisation, there is a decrease in the threshold of the peripheral chemoreflex response to carbon dioxide, which persists for at least 1 h after the return to normoxia. We suggest that ventilatory acclimatisation to hypoxia results from this decreased threshold, reflecting an increase in the activity of the peripheral chemoreflex. PMID:12562969

The vesicular glutamate transporter VGLUT3 contributes to protection against neonatal hypoxic stress

PubMed Central

Miot, Stéphanie; Voituron, Nicolas; Sterlin, Adélaïde; Vigneault, Erika; Morel, Lydie; Matrot, Boris; Ramanantsoa, Nelina; Amilhon, Bénédicte; Poirel, Odile; Lepicard, Ève; El Mestikawy, Salah; Hilaire, Gérard; Gallego, Jorge

2012-01-01

Neonates respond to hypoxia initially by increasing ventilation, and then by markedly decreasing both ventilation (hypoxic ventilatory decline) and oxygen consumption (hypoxic hypometabolism). This latter process, which vanishes with age, reflects a tight coupling between ventilatory and thermogenic responses to hypoxia. The neurological substrate of hypoxic hypometabolism is unclear, but it is known to be centrally mediated, with a strong involvement of the 5-hydroxytryptamine (5-HT, serotonin) system. To clarify this issue, we investigated the possible role of VGLUT3, the third subtype of vesicular glutamate transporter. VGLUT3 contributes to glutamate signalling by 5-HT neurons, facilitates 5-HT transmission and is expressed in strategic regions for respiratory and thermogenic control. We therefore assumed that VGLUT3 might significantly contribute to the response to hypoxia. To test this possibility, we analysed this response in newborn mice lacking VGLUT3 using anatomical, biochemical, electrophysiological and integrative physiology approaches. We found that the lack of VGLUT3 did not affect the histological organization of brainstem respiratory networks or respiratory activity under basal conditions. However, it impaired respiratory responses to 5-HT and anoxia, showing a marked alteration of central respiratory control. These impairments were associated with altered 5-HT turnover at the brainstem level. Furthermore, under cold conditions, the lack of VGLUT3 disrupted the metabolic rate, body temperature, baseline breathing and the ventilatory response to hypoxia. We conclude that VGLUT3 expression is dispensable under basal conditions but is required for optimal response to hypoxic stress in neonates. PMID:22890712

Hypercapnia attenuates ventilator-induced lung injury via a disintegrin and metalloprotease-17

PubMed Central

Otulakowski, Gail; Engelberts, Doreen; Gusarova, Galina A; Bhattacharya, Jahar; Post, Martin; Kavanagh, Brian P

2014-01-01

Hypercapnic acidosis, common in mechanically ventilated patients, has been reported to exert both beneficial and harmful effects in models of lung injury. Understanding its effects at the molecular level may provide insight into mechanisms of injury and protection. The aim of this study was to establish the effects of hypercapnic acidosis on mitogen-activated protein kinase (MAPK) activation, and determine the relevant signalling pathways. p44/42 MAPK activation in a murine model of ventilator-induced lung injury (VILI) correlated with injury and was reduced in hypercapnia. When cultured rat alveolar epithelial cells were subjected to cyclic stretch, activation of p44/42 MAPK was dependent on epidermal growth factor receptor (EGFR) activity and on shedding of EGFR ligands; exposure to 12% CO2 without additional buffering blocked ligand shedding, as well as EGFR and p44/42 MAPK activation. The EGFR ligands are known substrates of the matrix metalloprotease ADAM17, suggesting stretch activates and hypercapnic acidosis blocks stretch-mediated activation of ADAM17. This was corroborated in the isolated perfused mouse lung, where elevated CO2 also inhibited stretch-activated shedding of the ADAM17 substrate TNFR1 from airway epithelial cells. Finally, in vivo confirmation was obtained in a two-hit murine model of VILI where pharmacological inhibition of ADAM17 reduced both injury and p44/42 MAPK activation. Thus, ADAM17 is an important proximal mediator of VILI; its inhibition is one mechanism of hypercapnic protection and may be a target for clinical therapy. PMID:25085885

Control of cardiorespiratory function in response to hypoxia in an air-breathing fish, the African sharptooth catfish, Clarias gariepinus.

PubMed

Belão, T C; Zeraik, V M; Florindo, L H; Kalinin, A L; Leite, C A C; Rantin, F T

2015-09-01

We evaluated the role of the first pair of gill arches in the control of cardiorespiratory responses to normoxia and hypoxia in the air-breathing catfish, Clarias gariepinus. An intact group (IG) and an experimental group (EG, bilateral excision of first gill arch) were submitted to graded hypoxia, with and without access to air. The first pair of gill arches ablations reduced respiratory surface area and removed innervation by cranial nerve IX. In graded hypoxia without access to air, both groups displayed bradycardia and increased ventilatory stroke volume (VT), and the IG showed a significant increase in breathing frequency (fR). The EG exhibited very high fR in normoxia that did not increase further in hypoxia, this was linked to reduced O2 extraction from the ventilatory current (EO2) and a significantly higher critical O2 tension (PcO2) than the IG. In hypoxia with access to air, only the IG showed increased air-breathing, indicating that the first pair of gill arches excision severely attenuated air-breathing responses. Both groups exhibited bradycardia before and tachycardia after air-breaths. The fH and gill ventilation amplitude (VAMP) in the EG were overall higher than the IG. External and internal NaCN injections revealed that O2 chemoreceptors mediating ventilatory hypoxic responses (fR and VT) are internally oriented. The NaCN injections indicated that fR responses were mediated by receptors predominantly in the first pair of gill arches but VT responses by receptors on all gill arches. Receptors eliciting cardiac responses were both internally and externally oriented and distributed on all gill arches or extra-branchially. Air-breathing responses were predominantly mediated by receptors in the first pair of gill arches. In conclusion, the role of the first pair of gill arches is related to: (a) an elevated EO2 providing an adequate O2 uptake to maintain the aerobic metabolism during normoxia; (b) a significant bradycardia and increased fAB elicited by externally oriented O2 chemoreceptors; (c) increase in the ventilatory variables (fR and VAMP) stimulated by internally oriented O2 chemoreceptors. Copyright © 2015 Elsevier Inc. All rights reserved.

Determinants of noninvasive ventilation success or failure in morbidly obese patients in acute respiratory failure.

PubMed

Lemyze, Malcolm; Taufour, Pauline; Duhamel, Alain; Temime, Johanna; Nigeon, Olivier; Vangrunderbeeck, Nicolas; Barrailler, Stéphanie; Gasan, Gaëlle; Pepy, Florent; Thevenin, Didier; Mallat, Jihad

2014-01-01

Acute respiratory failure (ARF) is a common life-threatening complication in morbidly obese patients with obesity hypoventilation syndrome (OHS). We aimed to identify the determinants of noninvasive ventilation (NIV) success or failure for this indication. We prospectively included 76 consecutive patients with BMI>40 kg/m2 diagnosed with OHS and treated by NIV for ARF in a 15-bed ICU of a tertiary hospital. NIV failed to reverse ARF in only 13 patients. Factors associated with NIV failure included pneumonia (n = 12/13, 92% vs n = 9/63, 14%; p<0.0001), high SOFA (10 vs 5; p<0.0001) and SAPS2 score (63 vs 39; p<0.0001) at admission. These patients often experienced poor outcome despite early resort to endotracheal intubation (in-hospital mortality, 92.3% vs 17.5%; p<0.001). The only factor significantly associated with successful response to NIV was idiopathic decompensation of OHS (n = 30, 48% vs n = 0, 0%; p = 0.001). In the NIV success group (n = 63), 33 patients (53%) experienced a delayed response to NIV (with persistent hypercapnic acidosis during the first 6 hours). Multiple organ failure and pneumonia were the main factors associated with NIV failure and death in morbidly obese patients in hypoxemic ARF. On the opposite, NIV was constantly successful and could be safely pushed further in case of severe hypercapnic acute respiratory decompensation of OHS.

Effect of continuous dialysis on blood ph in acidemic hypercapnic animals with severe acute kidney injury: a randomized experimental study comparing high vs. low bicarbonate affluent.

PubMed

Romano, Thiago Gomes; Azevedo, Luciano Cesar Pontes; Mendes, Pedro Vitale; Costa, Eduardo Leite Vieira; Park, Marcelo

2017-12-01

Controlling blood pH during acute ventilatory failure and hypercapnia in individuals suffering from severe acute kidney injury (AKI) and undergoing continuous renal replacement therapy (CRRT) is of paramount importance in critical care settings. In this situation, the optimal concentration of sodium bicarbonate in the dialysate is still an unsolved question in critical care since high concentrations may worsen carbon dioxide levels and low concentrations may not be as effective in controlling pH. We performed a randomized, non-blinded, experimental study. AKI was induced in 12 female pigs via renal hilum ligation and hypoventilation by reducing the tidal volume during mechanical ventilation with the goal of achieving a pH between 7.10-7.15. After achieving the target pH, animals were randomized to undergo isovolemic hemodialysis with one of two bicarbonate concentrations in the dialysate (40 mEq/L [group 40] vs. 20 mEq/L [group 20]). Hemodynamic, respiratory, and laboratory data were collected. The median pH value at CRRT initiation was 7.14 [7.12, 7.15] in group 20 and 7.13 [7.09, 7.14] in group 40 (P = ns). The median baseline PaCO 2 was 74 [72, 81] mmHg in group 20 vs. 79 [63, 85] mmHg in group 40 (P = ns). After 3 h of CRRT, the pH value was 7.05 [6.95, 7.09] in group 20 and 7.12 [7.1, 7.14] in group 40 (P < 0.05), with corresponding values of PaCO 2 of 85 [79, 88] mmHg vs. 81 [63, 100] mmHg (P = ns). The difference in pH after 3 h was due to a metabolic component [standard base excess -10.4 [-12.5, -9.5] mEq/L in group 20 vs. -7.6 [-9.2, -5.1] mEq/L in group 40) (P < 0.05)]. Despite the increased infusion of bicarbonate in group 40, the blood CO 2 content did not change during the experiment. The 12-h survival rate was higher in group 40 (67% vs. 0, P = 0.032). A higher bicarbonate concentration in the dialysate of animals undergoing hypercapnic respiratory failure was associated with improved blood pH control without increasing the PaCO 2 levels.

Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats

PubMed Central

Henderson, Fraser; May, Walter J.; Gruber, Ryan B.; Discala, Joseph F.; Puscovic, Veljko; Young, Alex P.; Baby, Santhosh M.; Lewis, Stephen J.

2015-01-01

This study determined the effects of the peripherally restricted µ-opiate receptor (µ-OR) antagonist, naloxone methiodide (NLXmi) on fentanyl (25 µg/kg, i.v.)-induced changes in (1) analgesia, (2) arterial blood gas chemistry (ABG) and alveolar-arterial gradient (A-a gradient), and (3) ventilatory parameters, in conscious rats. The fentanyl-induced increase in analgesia was minimally affected by a 1.5 mg/kg of NLXmi but was attenuated by a 5.0 mg/kg dose. Fentanyl decreased arterial blood pH, pO2 and sO2 and increased pCO2 and A-a gradient. These responses were markedly diminished in NLXmi (1.5 mg/kg)-pretreated rats. Fentanyl caused ventilatory depression (e.g., decreases in tidal volume and peak inspiratory flow). Pretreatment with NLXmi (1.5 mg/kg, i.v.) antagonized the fentanyl decrease in tidal volume but minimally affected the other responses. These findings suggest that (1) the analgesia and ventilatory depression caused by fentanyl involve peripheral µ-ORs and (2) NLXmi prevents the fentanyl effects on ABG by blocking the negative actions of the opioid on tidal volume and A-a gradient. PMID:24284037

Lung function in the absence of respiratory symptoms in overweight children and adolescents*

PubMed Central

de Assunção, Silvana Neves Ferraz; Daltro, Carla Hilário da Cunha; Boa Sorte, Ney Christian; Ribeiro, Hugo da Costa; Bastos, Maria de Lourdes; Queiroz, Cleriston Farias; Lemos, Antônio Carlos Moreira

2014-01-01

OBJECTIVE: To describe lung function findings in overweight children and adolescents without respiratory disease. METHODS: This was a cross-sectional study involving male and female overweight children and adolescents in the 8-18 year age bracket, without respiratory disease. All of the participants underwent anthropometric assessment, chest X-ray, pulse oximetry, spirometry, and lung volume measurements. Individuals with respiratory disease were excluded, as were those who were smokers, those with abnormal chest X-rays, and those with an SpO2 = 92%. Waist circumference was measured in centimeters. The body mass index-for-age Z score for boys and girls was used in order to classify the individuals as overweight, obese, or severely obese. Lung function variables were expressed in percentage of the predicted value and were correlated with the anthropometric indices. RESULTS: We included 59 individuals (30 males and 29 females). The mean age was 11.7 ± 2.7 years. Lung function was normal in 21 individuals (35.6%). Of the 38 remaining individuals, 19 (32.2%), 15 (25.4%), and 4 (6.7%) presented with obstructive, restrictive, and mixed ventilatory disorder, respectively. The bronchodilator response was positive in 15 individuals (25.4%), and TLC measurements revealed that all of the individuals with reduced VC had restrictive ventilatory disorder. There were significant negative correlations between the anthropometric indices and the Tiffeneau index in the individuals with mixed ventilatory disorder. CONCLUSIONS: Lung function was abnormal in approximately 65% of the individuals evaluated here, all of whom were overweight. Obstructive ventilatory disorder and positive bronchodilator response predominated. PMID:24831397

Effects of Short-Term Acclimatization at the Summit of Mt. Fuji (3776 m) on Sleep Efficacy, Cardiovascular Responses, and Ventilatory Responses.

PubMed

Horiuchi, Masahiro; Oda, Shiro; Uno, Tadashi; Endo, Junko; Handa, Yoko; Fukuoka, Yoshiyuki

2017-06-01

Horiuchi, Masahiro, Shiro Oda, Tadashi Uno, Junko Endo, Yoko Handa, and Yoshiyuki Fukuoka. Effects of short-term acclimatization at the summit of Mt. Fuji (3776 m) on sleep efficacy, cardiovascular responses, and ventilatory responses. High Alt Med Biol. 18:171-178, 2017.-We investigated the effects of a short period of acclimatization, at 3776 m on Mt. Fuji, on sleep parameters and related physiological responses. Physiological responses were assessed in seven healthy lowlander men during both daytime and sleep while at sea level (SL), as well as for three consecutive nights at high altitude (HA; 3776 m, day 1 [D1], D2, D3, and morning only of D4). Blood pressure variables, heart rate (HR), pulmonary ventilation (V E ), and breathing frequency (Bf) progressively increased each day, with significant differences between SL and HA (p < 0.05, respectively). In contrast, end-tidal PCO 2 (P ET CO 2 ) progressively decreased each day with statistical differences between SL and D3 at HA (p < 0.05). During sleep at HA, mean arterial pressure (MAP) was stable, whereas it decreased during sleep at SL. Sleep efficacy, which was assessed by actigraphy, was linearly impaired with statistical differences between SL and D3 (p < 0.05). These impairments in sleep efficacy at HA were associated with higher MAP and HR, as well as lower Bf and P ET CO 2 during the daytime (pooled data, p < 0.05, respectively). These results suggest that hypoxia-induced cardiovascular and ventilatory responses may be crucial contributors to changes in sleep efficacy at HA.

Exercise responses in patients with chronically high creatine kinase levels.

PubMed

Cooper, Christopher B; Dolezal, Brett A; Neufeld, Eric V; Shieh, Perry; Jenner, John R; Riley, Marshall

2017-08-01

Elevated serum creatine kinase (CK) is often taken to reflect muscle disease, but many individuals have elevated CK without a specific diagnosis. How elevated CK reflects muscle metabolism during exercise is not known. Participants (46 men, 48 women) underwent incremental exercise testing to assess aerobic performance, cardiovascular response, and ventilatory response. Serum lactate, ammonia, and CK were measured at rest, 4 minutes into exercise, and 2 minutes into recovery. High-CK and control subjects demonstrated similar aerobic capacities and cardiovascular responses to incremental exercise. Those with CK ≥ 300 U/L exhibited significantly higher lactate and ammonia levels after maximal exercise, together with increased ventilatory responses, whereas those with CK ≥200 U/L but ≤ 300 U/L did not. We recommend measurement of lactate and ammonia profiles during a maximal incremental exercise protocol to help identify patients who warrant muscle biopsy to rule out myopathy. Muscle Nerve 56: 264-270, 2017. © 2016 Wiley Periodicals, Inc.

Occlusion pressures in men rebreathing CO2 under methoxyflurane anesthesia.

PubMed

Derenne, J P; Couture, J; Iscoe, S; Whitelaw, A; Milic-Emili, J

1976-05-01

The effect of general anesthesia on control of breathing was studied by CO2 rebreathing and occlusion pressure measurements in six normal human subjects under methoxyflurane anesthesia. CO2 was found to increase the amplitude of the occlusion pressure wave without changing its shape, so that CO2 responses in terms of the occlusion pressure developed 100 ms after the onset of inspiration (Po/0.1) gave results equivalent to the responses in terms of Po/1.o or any other parameter of the pressure wave. Methoxyflurane depressed the ventilatory response to CO2 but not the occlusion pressure response, implying that the most important action of the anesthetic was to increase the effective elastance of the respiratory system rather than to depress the respiratory centers. The elastance was further increased by CO2, and this mechanical change had the effect of shifting the "apneic threshold" extrapolated from the ventilatory response curve to a lower PAco2. Frequency of breathing, inspiratory and expiratory times were not altered by CO2 in anesthetized subjects.

Ventilatory responses to exercise training in obese adolescents.

PubMed

Mendelson, Monique; Michallet, Anne-Sophie; Estève, François; Perrin, Claudine; Levy, Patrick; Wuyam, Bernard; Flore, Patrice

2012-10-15

The aim of this study was to examine ventilatory responses to training in obese adolescents. We assessed body composition, pulmonary function and ventilatory responses (among which expiratory flow limitation and operational lung volumes) during progressive cycling exercise in 16 obese adolescents (OB) before and after 12 weeks of exercise training and in 16 normal-weight volunteers. As expected, obese adolescents' resting expiratory reserve volume was lower and inversely correlated with thoraco-abdominal fat mass (r = -0.74, p<0.0001). OB presented lower end expiratory (EELV) and end inspiratory lung volumes (EILV) at rest and during submaximal exercise, and modest expiratory flow limitation. After training, OB increased maximal aerobic performance (+19%) and maximal inspiratory pressure (93.7±31.4 vs. 81.9±28.2 cm H2O, +14%) despite lack of decrease in trunk fat and body weight. Furthermore, EELV and EILV were greater during submaximal exercise (+11% and +9% in EELV and EILV, respectively), expiratory flow limitation delayed but was not accompanied by increased V(T). However, submaximal exertional symptoms (dyspnea and leg discomfort) were significantly decreased (-71.3% and -70.7%, respectively). Our results suggest that exercise training can improve pulmonary function at rest (static inspiratory muscle strength) and exercise (greater operating lung volumes and delayed expiratory flow limitation) but these modifications did not entirely account for improved dyspnea and exercise performance in obese adolescents. Copyright © 2012 Elsevier B.V. All rights reserved.

Respiratory response to toluene diisocyanate depends on prior frequency and concentration of dermal sensitization in mice.

PubMed

Vanoirbeek, Jeroen A J; Tarkowski, Maciej; Ceuppens, Jan L; Verbeken, Erik K; Nemery, Benoit; Hoet, Peter H M

2004-08-01

Occupational asthma is the principal cause of work-related respiratory disease in the industrial world. In the absence of satisfactory models for predicting the potential of low molecular weight chemicals to cause asthma, we verified that dermal sensitization prior to intranasal challenge influences the respiratory response using toluene diisocyanate (TDI), a known respiratory sensitizer. BALB/c mice received TDI or vehicle (acetone/olive oil) on each ear on three consecutive days (days 1, 2, and 3; 0.3 or 3% TDI) or only once (day 1, 1% TDI). On day 7, the mice received similar dermal applications of vehicle or the same concentration of TDI as before ("boost"). On day 10, they received an intranasal dose of TDI (0.1%) or vehicle. Ventilatory function was monitored by whole body plethysmography for 40 min after intranasal application, and reactivity to inhaled methacholine was assessed 24 h later. Pulmonary inflammation was assessed by bronchoalveolar lavage and histology. Mice that received an intranasal dose of TDI without having received a prior dermal application of TDI did not exhibit any ventilatory response or inflammatory changes compared to vehicle controls. In contrast, mice that had received prior application(s) of TDI, even if only on day 7, exhibited the following: ventilatory responses, compatible with bronchoconstriction, immediately after intranasal application with TDI; enhanced methacholine responsiveness 24 h later; and pulmonary inflammation characterized by neutrophils. This was, however, not the case in mice that received the highest dermal amount of TDI (3% on days 1, 2, and 3). These findings suggest that respiratory response to TDI depends on prior frequency and concentration of dermal sensitization in mice.

[Ventilatory dysfunction in motor neuron disease: when and how to act?].

PubMed

Rocha, J Afonso; Miranda, M J

2007-01-01

Amyotrophic lateral sclerosis is a devastating progressive neurodegenerative disorder, involving motor neurons in the cerebral cortex, brainstem and spinal cord. Mean duration of survival from the time of diagnosis is around 15 months, being pulmonary complications and respiratory failure responsible for more than 85% of deaths. Albeit the inevitability of respiratory failure and short-term death, standardized intervention protocols have been shown to significantly delay the need for invasive ventilatory support, thus prolonging survival and enhancing quality of life. The authors present an intervention protocol based on clinical progression and respiratory parameters. Decisions regarding initiation of non-invasive positive pressure ventilation (NIPPV) and mechanically assisted coughing, depend on development of symptoms of hypoventilation and on objective deterioration of respiratory parameters especially in what concerns bulbar muscle function. These include maximum inspiratory capacity (MIC), difference between MIC and vital capacity (MIC-VC), and assisted peak cough flow (PCF). These standardized protocols along with patient and caregivers education, allow for improved quality of life, prolonged survival and delay or eventually prevent the need for tracheotomy and invasive ventilatory support. Supplemental oxygen should be avoided in these patients, since it precludes use of oxymetry as feedback for titrating NIPPV and MAC, and is associated with decreased ventilatory drive and aggravated hypercapnia.

[Respiratory symptoms and obstructive ventilatory disorder in Tunisian woman exposed to biomass].

PubMed

Kwas, H; Rahmouni, N; Zendah, I; Ghedira, H

2017-04-01

In some Tunisian cities, especially semi-urbanized, the exposure to the smoke produced during combustion of the biomass, main source of pollution of indoor air, remains prevalent among non-smoking women. To assess the relationship between exposure to biomass smoke and the presence of obstructive ventilatory disorder in the non-smoking women in semi-urban areas of Tunisia. Cross etiological study, using a questionnaire, including 140 non-smoking women responsible for cooking and/or exposed during heating by traditional means with objective measurement of their respiratory functions. We found 81 women exposed to biomass for a period of≥20 hours-years and 59 unexposed women. Exposed women reported more respiratory symptoms namely exertional dyspnea and/or chronic cough than unexposed. Of the 140 women, 14 women have an FEV/FEV6<70% of which 13 are exposed to biomass. We found a correlation between respiratory symptoms and obstructive ventilatory disorder in exposed women. The air pollution inside the home during the traditional activities of cooking and/or heating is a respiratory risk factor for non-smoking women over the age of 30 years. Exposure to biomass smoke can cause chronic respiratory symptoms and persistent obstructive ventilatory disorder that can consistent with COPD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Fatty acid amide hydrolase-morphine interaction influences ventilatory response to hypercapnia and postoperative opioid outcomes in children.

PubMed

Chidambaran, Vidya; Pilipenko, Valentina; Spruance, Kristie; Venkatasubramanian, Raja; Niu, Jing; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; Zhang, Kejian; Kaufman, Kenneth; Vinks, Alexander A; Martin, Lisa J; Sadhasivam, Senthilkumar

2017-01-01

Fatty acid amide hydrolase (FAAH) degrades anandamide, an endogenous cannabinoid. We hypothesized that FAAH variants will predict risk of morphine-related adverse outcomes due to opioid-endocannabinoid interactions. In 101 postsurgical adolescents receiving morphine analgesia, we prospectively studied ventilatory response to 5% CO 2 (HCVR), respiratory depression (RD) and vomiting. Blood was collected for genotyping and morphine pharmacokinetics. We found significant FAAH-morphine interaction for missense (rs324420) and several regulatory variants, with HCVR (p < 0.0001) and vomiting (p = 0.0339). HCVR was more depressed in patients who developed RD compared with those who did not (p = 0.0034), thus FAAH-HCVR association predicts risk of impending RD from morphine use. FAAH genotypes predict risk for morphine-related adverse outcomes.

Emphysema on Thoracic CT and Exercise Ventilatory Inefficiency in Mild-to-Moderate COPD.

PubMed

Jones, Joshua H; Zelt, Joel T; Hirai, Daniel M; Diniz, Camilla V; Zaza, Aida; O'Donnell, Denis E; Neder, J Alberto

2017-04-01

There is growing evidence that emphysema on thoracic computed tomography (CT) is associated with poor exercise tolerance in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that an excessive ventilatory response to exercise (ventilatory inefficiency) would underlie these abnormalities. In a prospective study, 19 patients (FEV 1 = 82 ± 13%, 12 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1) and 26 controls underwent an incremental exercise test. Ventilatory inefficiency was assessed by the ventilation ([Formula: see text]E)/CO 2 output ([Formula: see text]CO 2 ) nadir. Pulmonary blood flow (PBF) in a submaximal test was calculated by inert gas rebreathing. Emphysema was quantified as % of attenuation areas below 950 HU. Patients typically presented with centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/total lung ratio = 0.82 ± 0.04). They had lower peak oxygen uptake ([Formula: see text]O 2 ), higher [Formula: see text]E/[Formula: see text]CO 2 nadir, and greater dyspnea scores than controls (p < 0.05). Lower peak [Formula: see text]O 2 and worse dyspnea were found in patients with higher [Formula: see text]E/[Formula: see text]CO 2 nadirs (≥30). Patients had blunted increases in PBF from rest to iso-[Formula: see text]O 2 exercise (p < 0.05). Higher [Formula: see text]E/[Formula: see text]CO 2 nadir in COPD was associated with emphysema severity (r = 0.63) which, in turn, was related to reduced lung diffusing capacity (r = -0.72) and blunted changes in PBF from rest to exercise (r = -0.69) (p < 0.01). Ventilation "wasted" in emphysematous areas is associated with impaired exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (D L CO) to a key clinical outcome (poor exercise tolerance) in COPD patients with only modest spirometric abnormalities.

AltitudeOmics: enhanced cerebrovascular reactivity and ventilatory response to CO2 with high-altitude acclimatization and reexposure.

PubMed

Fan, Jui-Lin; Subudhi, Andrew W; Evero, Oghenero; Bourdillon, Nicolas; Kayser, Bengt; Lovering, Andrew T; Roach, Robert C

2014-04-01

The present study is the first to examine the effect of high-altitude acclimatization and reexposure on the responses of cerebral blood flow and ventilation to CO2. We also compared the steady-state estimates of these parameters during acclimatization with the modified rebreathing method. We assessed changes in steady-state responses of middle cerebral artery velocity (MCAv), cerebrovascular conductance index (CVCi), and ventilation (V(E)) to varied levels of CO2 in 21 lowlanders (9 women; 21 ± 1 years of age) at sea level (SL), during initial exposure to 5,260 m (ALT1), after 16 days of acclimatization (ALT16), and upon reexposure to altitude following either 7 (POST7) or 21 days (POST21) at low altitude (1,525 m). In the nonacclimatized state (ALT1), MCAv and V(E) responses to CO2 were elevated compared with those at SL (by 79 ± 75% and 14.8 ± 12.3 l/min, respectively; P = 0.004 and P = 0.011). Acclimatization at ALT16 further elevated both MCAv and Ve responses to CO2 compared with ALT1 (by 89 ± 70% and 48.3 ± 32.0 l/min, respectively; P < 0.001). The acclimatization gained for V(E) responses to CO2 at ALT16 was retained by 38% upon reexposure to altitude at POST7 (P = 0.004 vs. ALT1), whereas no retention was observed for the MCAv responses (P > 0.05). We found good agreement between steady-state and modified rebreathing estimates of MCAv and V(E) responses to CO2 across all three time points (P < 0.001, pooled data). Regardless of the method of assessment, altitude acclimatization elevates both the cerebrovascular and ventilatory responsiveness to CO2. Our data further demonstrate that this enhanced ventilatory CO2 response is partly retained after 7 days at low altitude.

Ventilatory Dysfunction in Parkinson’s Disease

PubMed Central

Baille, Guillaume; De Jesus, Anna Maria; Perez, Thierry; Devos, David; Dujardin, Kathy; Charley, Christelle Monaca; Defebvre, Luc; Moreau, Caroline

2016-01-01

In contrast to some other neurodegenerative diseases, little is known about ventilatory dysfunction in Parkinson’s disease (PD). To assess the spectrum of ventilation disorders in PD, we searched for and reviewed studies of dyspnea, lung volumes, respiratory muscle function, sleep breathing disorders and the response to hypoxemia in PD. Among the studies, we identified some limitations: (i) small study populations (mainly composed of patients with advanced PD), (ii) the absence of long-term follow-up and (iii) the absence of functional evaluations under “off-drug” conditions. Although there are many reports of abnormal spirometry data in PD (mainly related to impairment of the inspiratory muscles), little is known about hypoventilation in PD. We conclude that ventilatory dysfunction in PD has been poorly studied and little is known about its frequency and clinical relevance. Hence, there is a need to characterize the different phenotypes of ventilation disorders in PD, study their relationships with disease progression and assess their prognostic value. PMID:27314755

Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats.

PubMed

Henderson, Fraser; May, Walter J; Gruber, Ryan B; Discala, Joseph F; Puskovic, Veljko; Young, Alex P; Baby, Santhosh M; Lewis, Stephen J

2014-01-15

This study determined the effects of the peripherally restricted μ-opiate receptor (μ-OR) antagonist, naloxone methiodide (NLXmi) on fentanyl (25μg/kg, i.v.)-induced changes in (1) analgesia, (2) arterial blood gas chemistry (ABG) and alveolar-arterial gradient (A-a gradient), and (3) ventilatory parameters, in conscious rats. The fentanyl-induced increase in analgesia was minimally affected by a 1.5mg/kg of NLXmi but was attenuated by a 5.0mg/kg dose. Fentanyl decreased arterial blood pH, pO2 and sO2 and increased pCO2 and A-a gradient. These responses were markedly diminished in NLXmi (1.5mg/kg)-pretreated rats. Fentanyl caused ventilatory depression (e.g., decreases in tidal volume and peak inspiratory flow). Pretreatment with NLXmi (1.5mg/kg, i.v.) antagonized the fentanyl decrease in tidal volume but minimally affected the other responses. These findings suggest that (1) the analgesia and ventilatory depression caused by fentanyl involve peripheral μ-ORs and (2) NLXmi prevents the fentanyl effects on ABG by blocking the negative actions of the opioid on tidal volume and A-a gradient. Copyright © 2013 Elsevier B.V. All rights reserved.

Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia.

PubMed

Fournier, Sébastien; Gulemetova, Roumiana; Baldy, Cécile; Joseph, Vincent; Kinkead, Richard

2015-04-01

Human and animal studies on sleep-disordered breathing and respiratory regulation show that the effects of sex hormones are heterogeneous. Because neonatal stress results in sex-specific disruption of the respiratory control in adult rats, we postulate that it might affect respiratory control modulation induced by ovarian steroids in female rats. The hypoxic ventilatory response (HVR) of adult female rats exposed to neonatal maternal separation (NMS) is ∼30% smaller than controls (24), but consequences of NMS on respiratory control in aging female rats are unknown. To address this issue, whole body plethysmography was used to evaluate the impact of NMS on the HVR (12% O2, 20 min) of middle-aged (MA; ∼57 wk old) female rats. Pups subjected to NMS were placed in an incubator 3 h/day for 10 consecutive days (P3 to P12). Controls were undisturbed. To determine whether the effects were related to sexual hormone decline or aging per se, experiments were repeated on bilaterally ovariectomized (OVX) young (∼12 wk old) adult female rats. OVX and MA both reduced the HVR significantly in control rats but had little effect on the HVR of NMS females. OVX (but not aging) reduced the anapyrexic response in both control and NMS animals. These results show that hormonal decline decreases the HVR of control animals, while leaving that of NMS female animals unaffected. This suggests that neonatal stress alters the interaction between sex hormone regulation and the development of body temperature, hormonal, and ventilatory responses to hypoxia. Copyright © 2015 the American Physiological Society.

The obstructive sleep apnoea syndrome in adolescents.

PubMed

Marcus, Carole L; Keenan, Brendan T; Huang, Jingtao; Yuan, Haibo; Pinto, Swaroop; Bradford, Ruth M; Kim, Christopher; Bagchi, Sheila; Comyn, Francois-Louis; Wang, Stephen; Tapia, Ignacio E; Maislin, Greg; Cielo, Christopher M; Traylor, Joel; Torigian, Drew A; Schwab, Richard J

2017-08-01

The obstructive sleep apnoea syndrome (OSAS) results from a combination of structural and neuromotor factors; however, the relative contributions of these factors have not been studied during the important developmental phase of adolescence. We hypothesised that adenotonsillar volume (ATV), nasopharyngeal airway volume (NPAV), upper airway critical closing pressure (Pcrit) in the hypotonic and activated neuromotor states, upper airway electromyographic response to subatmospheric pressure and the ventilatory response to CO 2 during sleep would be major predictors of OSAS risk. 42 obese adolescents with OSAS and 37 weight-matched controls underwent upper airway MRI, measurements of Pcrit, genioglossal electromyography and ventilatory response to CO 2 during wakefulness and sleep. ATV, NPAV, activated and hypotonic Pcrit, genioglossal electromyography and ventilatory response to CO 2 during sleep were all associated with OSAS risk. Multivariate models adjusted for age, gender, body mass index and race indicated that ATV, NPAV and activated Pcrit each independently affected apnoea risk in adolescents; genioglossal electromyography was independently associated in a reduced sample. There was significant interaction between NPAV and activated Pcrit (p=0.021), with activated Pcrit more strongly associated with OSAS in adolescents with larger NPAVs and NPAV more strongly associated with OSAS in adolescents with more negative activated closing pressure. OSAS in adolescents is mediated by a combination of anatomic (ATV, NPAV) and neuromotor factors (activated Pcrit). This may have important implications for the management of OSAS in adolescents. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats.

PubMed

Del Rio, Rodrigo; Andrade, David C; Lucero, Claudia; Arias, Paulina; Iturriaga, Rodrigo

2016-08-01

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O2, 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments. In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and increased arrhythmias and atrial fibrosis. CB ablation normalized blood pressure, reduced ventilatory response to hypoxia, and restored cardiac autonomic and baroreflex function. In addition, CB ablation reduced the number of arrhythmias, but not extracellular matrix remodeling or systemic oxidative stress, suggesting that reductions in arrhythmia incidence during CIH were related to normalization of cardiac autonomic balance. Present results show that autonomic alterations induced by CIH are critically dependent on the CB and support a main role for the CB in the CIH-induced hypertension. © 2016 American Heart Association, Inc.

Effect of airway acidosis and alkalosis on airway vascular smooth muscle responsiveness to albuterol.

PubMed

Cancado, Jose E; Mendes, Eliana S; Arana, Johana; Horvath, Gabor; Monzon, Maria E; Salathe, Matthias; Wanner, Adam

2015-04-02

In vitro and animal experiments have shown that the transport and signaling of β2-adrenergic agonists are pH-sensitive. Inhaled albuterol, a hydrophilic β2-adrenergic agonist, is widely used for the treatment of obstructive airway diseases. Acute exacerbations of obstructive airway diseases can be associated with changes in ventilation leading to either respiratory acidosis or alkalosis thereby affecting albuterol responsiveness in the airway. The purpose of this study was to determine if airway pH has an effect on albuterol-induced vasodilation in the airway. Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation (to dissociate the effect of pH from the effect of ventilation). During these breathing maneuvers, exhaled breath condensate (EBC) pH and airway blood flow response to inhaled albuterol (ΔQ̇aw) were assessed. Mean ± SE EBC pH (units) and ΔQ̇aw (μl.min(-1).mL(-1)) were 6.4 ± 0.1 and 16.8 ± 1.9 during quiet breathing, 6.3 ± 0.1 and 14.5 ± 2.4 during eucapnic hyperventilation, 6.6 ± 0.2 and -0.2 ± 1.8 during hypocapnic hyperventilation (p = 0.02 and <0.01 vs. quiet breathing), and 5.9 ± 0.1 and 2.0 ± 1.5 during hypercapnic hyperventilation (p = 0.02 and <0.02 vs quiet breathing). Albuterol responsiveness in the airway as assessed by ΔQ̇aw is pH sensitive. The breathing maneuver associated with decreased and increased EBC pH both resulted in a decreased responsiveness independent of the level of ventilation. These findings suggest an attenuated response to hydrophilic β2-adrenergic agonists during airway disease exacerbations associated with changes in pH. Registered at clinicaltrials.gov: NCT01216748 .

The prefrontal oxygenation and ventilatory responses at start of one-legged cycling exercise have relation to central command.

PubMed

Asahara, Ryota; Matsukawa, Kanji; Ishii, Kei; Liang, Nan; Endo, Kana

2016-11-01

When performing exercise arbitrarily, activation of central command should start before the onset of exercise, but when exercise is forced to start with cue, activation of central command should be delayed. We examined whether the in-advance activation of central command influenced the ventilatory response and reflected in the prefrontal oxygenation, by comparing the responses during exercise with arbitrary and cued start. The breath-by-breath respiratory variables and the prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) were measured during one-legged cycling. Minute ventilation (V̇e) at the onset of arbitrary one-legged cycling was augmented to a greater extent than cued cycling, while end-tidal carbon dioxide tension (ETco 2 ) decreased irrespective of arbitrary or cued start. Symmetric increase in the bilateral prefrontal Oxy-Hb occurred before and at the onset of arbitrary one-legged cycling, whereas such an increase was absent with cued start. The time course and magnitude of the increased prefrontal oxygenation were not influenced by the extent of subjective rating of perceived exertion and were the same as those of the prefrontal oxygenation during two-legged cycling previously reported. Mental imagery or passive performance of the one-legged cycling increased V̇e and decreased ETco 2 Neither intervention, however, augmented the prefrontal Oxy-Hb. The changes in ETco 2 could not explain the prefrontal oxygenation response during voluntary or passive one-legged cycling. Taken together, it is likely that the in-advance activation of central command influenced the ventilatory response by enhancing minute ventilation at the onset of one-legged cycling exercise and reflected in the preexercise increase in the prefrontal oxygenation. Copyright © 2016 the American Physiological Society.

Effects of fenoterol on ventilatory responses to hypoxia and hypercapnia in normal subjects.

PubMed Central

Yoshiike, Y.; Suzuki, S.; Watanuki, Y.; Okubo, T.

1995-01-01

BACKGROUND--The effects of beta 2 adrenergic agonists on chemoreceptors remain controversial. This study was designed to examine whether fenoterol, a beta 2 adrenergic agonist, increases the ventilatory responses to hypercapnia (HCVR) and hypoxia (HVR) in normal subjects. METHODS--HCVR was tested with a rebreathing method and HVR was examined with a progressive isocapnic hypoxic method in 11 normal subjects. Both HCVR and HVR were assessed by the slope of occlusion pressure (P0.1) or ventilation (VE) plotted against end tidal carbon dioxide pressure and arterial oxygen saturation, respectively. Respiratory muscle strength, spirometric values and lung volume were measured. After a single oral administration of 5 mg fenoterol or placebo HCVR and HVR were evaluated. RESULTS--Fenoterol treatment did not change the specific airway conductance or forced expiratory volume in one second. Respiratory muscle strength did not change. Fenoterol increased the slope of the HCVR of both P0.1 (from 0.251 (0.116) to 0.386 (0.206) kPa/kPa, average increase 71%) and VE (from 10.7 (3.4) to 15.1 (4.2) l/min/kPa, average increase 52%), and shifted the response curves to higher values. For the HVR fenoterol increased the slopes of both P0.1 and VE (from -4.06 (2.00) x 10(-3) to -7.99 (4.29) x 10(-3) kPa/%, an average increase of 83%, and from -0.221 (0.070) to -0.313 (0.112) l/min/%, a 44.5% increase, respectively), and shifted the response curves to higher values. CONCLUSION--Acute administration of fenoterol increases the ventilatory responses to both hypercapnia and hypoxia in normal subjects. PMID:7701451

Prenatal nicotine exposure increases hyperventilation in α4-knock-out mice during mild asphyxia.

PubMed

Avraam, Joanne; Cohen, Gary; Drago, John; Frappell, Peter B

2015-03-01

Prenatal nicotine exposure alters breathing and ventilatory responses to stress through stimulation of nicotine acetylcholine receptors (nAChRs). We tested the hypothesis that α4-containing nAChRs are involved in mediating the effects of prenatal nicotine exposure on ventilatory and metabolic responses to intermittent mild asphyxia (MA). Using open-flow plethysmography, we measured ventilation (V̇(E)) and rate of O2 consumption ( V̇(O2)) of wild-type (WT) and α4-knock-out (KO) mice, at postnatal (P) days 1-2 and 7-8, with and without prenatal nicotine exposure (6 mg kg(-1) day(-1) beginning on embryonic day 14). Mice were exposed to seven 2 min cycles of mild asphyxia (10% O2 and 5% CO2), each interspersed with 2 min of air. Compared to WT, α4 KO mice had increased air V̇(E) and V̇(O2) at P7-8, but not P1-2. Irrespective of age, genotype had no effect on the hyperventilatory response (increase in V̇(E)/V̇(O2)) to MA. At P1-2, nicotine suppressed air V̇(E) and V̇(O2) in both genotypes but did not affect the hyperventilatory response to MA. At P7-8 nicotine suppressed air V̇(E) and V̇(O2) of only α4 KO's but also significantly enhanced V̇(E) during MA (nearly double that of WT; p<0.001). This study has revealed complex effects of α4 nAChR deficiency and prenatal nicotine exposure on ventilatory and metabolic interactions and responses to stress. Copyright © 2015 Elsevier B.V. All rights reserved.

An Improved Dynamic Model for the Respiratory Response to Exercise

PubMed Central

Serna, Leidy Y.; Mañanas, Miguel A.; Hernández, Alher M.; Rabinovich, Roberto A.

2018-01-01

Respiratory system modeling has been extensively studied in steady-state conditions to simulate sleep disorders, to predict its behavior under ventilatory diseases or stimuli and to simulate its interaction with mechanical ventilation. Nevertheless, the studies focused on the instantaneous response are limited, which restricts its application in clinical practice. The aim of this study is double: firstly, to analyze both dynamic and static responses of two known respiratory models under exercise stimuli by using an incremental exercise stimulus sequence (to analyze the model responses when step inputs are applied) and experimental data (to assess prediction capability of each model). Secondly, to propose changes in the models' structures to improve their transient and stationary responses. The versatility of the resulting model vs. the other two is shown according to the ability to simulate ventilatory stimuli, like exercise, with a proper regulation of the arterial blood gases, suitable constant times and a better adjustment to experimental data. The proposed model adjusts the breathing pattern every respiratory cycle using an optimization criterion based on minimization of work of breathing through regulation of respiratory frequency. PMID:29467674

Fatty acid amide hydrolase–morphine interaction influences ventilatory response to hypercapnia and postoperative opioid outcomes in children

PubMed Central

Chidambaran, Vidya; Pilipenko, Valentina; Spruance, Kristie; Venkatasubramanian, Raja; Niu, Jing; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; Zhang, Kejian; Kaufman, Kenneth; Vinks, Alexander A; Martin, Lisa J; Sadhasivam, Senthilkumar

2017-01-01

Aim: Fatty acid amide hydrolase (FAAH) degrades anandamide, an endogenous cannabinoid. We hypothesized that FAAH variants will predict risk of morphine-related adverse outcomes due to opioid–endocannabinoid interactions. Patients & methods: In 101 postsurgical adolescents receiving morphine analgesia, we prospectively studied ventilatory response to 5% CO2 (HCVR), respiratory depression (RD) and vomiting. Blood was collected for genotyping and morphine pharmacokinetics. Results: We found significant FAAH–morphine interaction for missense (rs324420) and several regulatory variants, with HCVR (p < 0.0001) and vomiting (p = 0.0339). HCVR was more depressed in patients who developed RD compared with those who did not (p = 0.0034), thus FAAH–HCVR association predicts risk of impending RD from morphine use. Conclusion: FAAH genotypes predict risk for morphine-related adverse outcomes. PMID:27977335

Association between angiotensin-converting enzyme gene polymorphisms and exercise performance in patients with COPD.

PubMed

Zhang, Xiaolei; Wang, Chen; Dai, Huaping; Lin, Yingxiang; Zhang, Jun

2008-09-01

Recent studies have shown that polymorphisms of the angiotensin-converting enzyme (ACE) gene are closely associated with pulmonary disorders. The ACE gene is involved in the regulation of inflammatory reactions to lung injury, respiratory drive, erythropoiesis and tissue oxygenation. The hypothesis for this study was that the ACE gene may be associated with the ventilatory response to exercise and the aerobic work efficiency of skeletal muscle in patients with COPD. Sixty-one Chinese Han COPD patients and 57 healthy control subjects performed incremental cardiopulmonary exercise testing on a cycle ergometer. ACE genotypes were determined using PCR amplification. Resting lung function and blood gas index were not significantly different among the three ACE genotype COPD groups. Similarly, there were no significant differences in AT, maximal O(2) uptake, maximal O(2) pulse, maximal dyspnoea index, ventilatory response (DeltaVE/DeltaVCO(2)), O(2) cost of ventilation (VO(2)/W/VE), end-tidal partial pressure of carbon dioxide at maximal exercise and maximal SaO(2) among the three ACE genotype COPD patients. Maximal work load and aerobic work efficiency were higher in the COPD group with the II genotype than in those with the ID or DD genotype. There were no significant differences in resting lung function and cardiopulmonary exercise testing parameters among the three ACE genotype control groups. The ACE gene may be involved in the regulation of skeletal muscle aerobic work efficiency, but is not associated with the ventilatory responses to exercise in COPD patients.

Peripheral chemoreceptor activity in sleeping neonates exposed to warm environments.

PubMed

Chardon, K; Bach, V; Telliez, F; Tourneux, P; Elabbassi, E B; Cardot, V; Gaultier, C; Libert, J P

2003-09-01

In neonates, it is often assumed that ventilatory control and heat stress interact. Thus the two factors have been implicated in various pathologies (apnoea, sudden infant death syndrome). However, little is known about the mechanisms of this interaction, and the influence of sleep is still debated. This study aimed at determining the influence of warm exposure on the decrease in ventilation during a hyperoxic test (HT), which is considered to be a measure of peripheral chemoreceptor activity. The test was performed in active (AS) and quiet sleep (QS) in 12 neonates exposed to thermoneutral or warm environments. The HT consisted of 30 s of inspired, 100% O(2). The ventilatory response was assessed in terms of a response time, defined as the time elapsing between HT onset and the first significant change in V(E). Our results show that, in both thermal conditions, the fall in V(E) was higher in AS than in QS. Warm exposure significantly enhanced the ventilatory response in AS (-27.5 +/- 8.7% vs. -38.3 +/- 8.8%, P < 0.01) but not in QS. A thermometabolic drive or inputs from thermoreceptors could be involved in the reinforcement of peripheral chemoreceptor activity in AS in warmer environments, which could contribute to an increasing risk of apnoea in neonates with altered chemoreceptor function. Since hypothalamic structures are involved in thermoregulatory, sleep processes and (probably) in respiratory control, it could well be the principal site where this interaction occurs.

Ventilatory drive is enhanced in male and female rats following chronic intermittent hypoxia.

PubMed

Edge, D; Skelly, J R; Bradford, A; O'Halloran, K D

2009-01-01

Obstructive sleep apnoea is characterized by chronic intermittent hypoxia (CIH) due to recurrent apnoea. We have developed a rat model of CIH, which shows evidence of impaired respiratory muscle function. In this study, we wished to characterize the ventilatory effects of CIH in conscious male and female animals. Adult male (n=14) and female (n=8) Wistar rats were used. Animals were placed in chambers daily for 8 h with free access to food and water. The gas supply to one half of the chambers alternated between air and nitrogen every 90 s, for 8 h per day, reducing ambient oxygen concentration in the chambers to 5% at the nadir (intermittent hypoxia; n=7 male, n=4 female). Air supplying the other chambers was switched every 90 s to air from a separate source, at the same flow rates, and animals in these chambers served as controls (n=7 male, n=4 female). Ventilatory measurements were made in conscious animals (typically sleeping) after 10 days using whole-body plethysmography. Normoxic ventilation was increased in both male and female CIH-treated rats compared to controls but this did not achieve statistical significance. However, ventilatory drive was increased in CIH-treated rats of both sexes as evidenced by significant increases in mean and peak inspiratory flow. Ventilatory responses to acute hypoxia (F(I)O(2) = 0.10; 6 min) and hyperoxic hypercapnia (F(I)CO(2) = 0.05; 6 min) were unaffected by CIH treatment in male and female rats (P>0.05, ANOVA). We conclude that CIH increases respiratory drive in adult rats. We speculate that this represents a form of neural plasticity that may compensate for respiratory muscle impairment that occurs in this animal model.

Development of an anaesthetized-rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram.

PubMed

Miyamoto, Tadayoshi; Manabe, Kou; Ueda, Shinya; Nakahara, Hidehiro

2018-05-01

What is the central question of this study? The lack of useful small-animal models for studying exercise hyperpnoea makes it difficult to investigate the underlying mechanisms of exercise-induced ventilatory abnormalities in various disease states. What is the main finding and its importance? We developed an anaesthetized-rat model for studying exercise hyperpnoea, using a respiratory equilibrium diagram for quantitative characterization of the respiratory chemoreflex feedback system. This experimental model will provide an opportunity to clarify the major determinant mechanisms of exercise hyperpnoea, and will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. Exercise-induced ventilatory abnormalities in various disease states seem to arise from pathological changes of respiratory regulation. Although experimental studies in small animals are essential to investigate the pathophysiological basis of various disease models, the lack of an integrated framework for quantitatively characterizing respiratory regulation during exercise prevents us from resolving these problems. The purpose of this study was to develop an anaesthetized-rat model for studying exercise hyperpnoea for quantitative characterization of the respiratory chemoreflex feedback system. In 24 anaesthetized rats, we induced muscle contraction by stimulating bilateral distal sciatic nerves at low and high voltage to mimic exercise. We recorded breath-by-breath respiratory gas analysis data and cardiorespiratory responses while running two protocols to characterize the controller and plant of the respiratory chemoreflex. The controller was characterized by determining the linear relationship between end-tidal CO 2 pressure (P ETC O2) and minute ventilation (V̇E), and the plant by the hyperbolic relationship between V̇E and P ETC O2. During exercise, the controller curve shifted upward without change in controller gain, accompanying increased oxygen uptake. The hyperbolic plant curve shifted rightward and downward depending on exercise intensity as predicted by increased metabolism. Exercise intensity-dependent changes in operating points (V̇E and P ETC O2) were estimated by integrating the controller and plant curves in a respiratory equilibrium diagram. In conclusion, we developed an anaesthetized-rat model for studying exercise hyperpnoea, using systems analysis for quantitative characterization of the respiratory system. This novel experimental model will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. © 2018 Morinomiya University of Medical Sciences. Experimental Physiology © 2018 The Physiological Society.

Humidification during high-frequency oscillation ventilation is affected by ventilator circuit and ventilatory setting.

PubMed

Chikata, Yusuke; Imanaka, Hideaki; Onishi, Yoshiaki; Ueta, Masahiko; Nishimura, Masaji

2009-08-01

High-frequency oscillation ventilation (HFOV) is an accepted ventilatory mode for acute respiratory failure in neonates. As conventional mechanical ventilation, inspiratory gas humidification is essential. However, humidification during HFOV has not been clarified. In this bench study, we evaluated humidification during HFOV in the open circumstance of ICU. Our hypothesis is that humidification during HFOV is affected by circuit design and ventilatory settings. We connected a ventilator with HFOV mode to a neonatal lung model that was placed in an infant incubator set at 37 degrees C. We set a heated humidifier (Fisher & Paykel) to obtain 37 degrees C at the chamber outlet and 40 degrees C at the distal temperature probe. We measured absolute humidity and temperature at the Y-piece using a rapid-response hygrometer. We evaluated two types of ventilator circuit: a circuit with inner heating wire and another with embedded heating element. In addition, we evaluated three lengths of the inspiratory limb, three stroke volumes, three frequencies, and three mean airway pressures. The circuit with embedded heating element provided significantly higher absolute humidity and temperature than one with inner heating wire. As an extended tube lacking a heating wire was shorter, absolute humidity and temperature became higher. In the circuit with inner heating wire, absolute humidity and temperature increased as stroke volume increased. Humidification during HFOV is affected by circuit design and ventilatory settings.

[Respiratory symptoms and obstructive ventilatory disorder in Tunisian woman exposed to biomass].

PubMed

Kwas, H; Rahmouni, N; Zendah, I; Ghédira, H

2017-06-01

In some Tunisian cities, especially semi-urbanized, the exposure to the smoke produced during combustion of the biomass, main source of pollution of indoor air, remains prevalent among non-smoking women. To assess the relationship between exposure to biomass smoke and the presence of obstructive ventilatory disorder in the non-smoking women in semi-urban areas of Tunisia. Cross etiological study, using a questionnaire, including 140 non-smoking women responsible for cooking and/or exposed during heating by traditional means with objective measurement of their respiratory functions. We found 81 women exposed to biomass for a period > or equal to 20 hours-years and 59 unexposed women. Exposed women reported more respiratory symptoms namely exertional dyspnea and/or chronic cough than unexposed. Of the 140 women, 14 women have an FEV/FEV6 <70 % of which 13 are exposed to biomass. We found a correlation between respiratory symptoms and obstructive ventilatory disorder in exposed women. The air pollution inside the home during the traditional activities of cooking and/or heating is a respiratory risk factor for non-smoking women over the age of 30 years. Exposure to biomass smoke can cause chronic respiratory symptoms and persistent obstructive ventilatory disorder that can be consistent with COPD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Exercise Ventilatory Limitation: The Role Of Expiratory Flow Limitation

PubMed Central

Babb, Tony G.

2012-01-01

Ventilatory limitation to exercise remains an important unresolved clinical issue; as a result, many individuals misinterpret the effects of expiratory flow limitation as an all-or-nothing phenomenon. Expiratory flow limitation is not all-or-none; approaching maximal expiratory flow can have important effects not only on ventilatory capacity but also on breathing mechanics, ventilatory control, and possibly exertional dyspnea and exercise intolerance. PMID:23038244

Organophosphate-induced intermediate syndrome: aetiology and relationships with myopathy.

PubMed

Karalliedde, Lakshman; Baker, David; Marrs, Timothy C

2006-01-01

The intermediate syndrome (IMS) following organophosphorus (OP) insecticide poisoning was first described in the mid-1980s. The syndrome described comprised characteristic symptoms and signs occurring after apparent recovery from the acute cholinergic syndrome. As the syndrome occurred after the acute cholinergic syndrome but before organophosphate-induced delayed polyneuropathy, the syndrome was called 'intermediate syndrome'. The IMS occurs in approximately 20% of patients following oral exposure to OP pesticides, with no clear association between the particular OP pesticide involved and the development of the syndrome. It usually becomes established 2-4 days after exposure when the symptoms and signs of the acute cholinergic syndrome (e.g. muscle fasciculations, muscarinic signs) are no longer obvious. The characteristic features of the IMS are weakness of the muscles of respiration (diaphragm, intercostal muscles and accessory muscles including neck muscles) and of proximal limb muscles. Accompanying features often include weakness of muscles innervated by some cranial nerves. It is now emerging that the degree and extent of muscle weakness may vary following the onset of the IMS. Thus, some patients may only have weakness of neck muscles whilst others may have weakness of neck muscles and proximal limb muscles. These patients may not require ventilatory care but close observation and monitoring of respiratory function is mandatory. Management is essentially that of rapidly developing respiratory distress and respiratory failure. Delays in instituting ventilatory care will result in death. Initiation of ventilatory care and maintenance of ventilatory care often requires minimal doses of non-depolarising muscle relaxants. The use of depolarising muscle relaxants such as suxamethonium is contraindicated in OP poisoning. The duration of ventilatory care required by patients may differ considerably and it is usual for patients to need ventilatory support for 7-15 days and even up to 21 days. Weaning from ventilatory care is best carried out in stages, with provision of continuous positive airway pressure prior to complete weaning. Continuous and close monitoring of respiratory function (arterial oxygen saturation, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood) and acid-base status are an absolute necessity. Prophylactic antibiotics are usually not required unless there has been evidence of aspiration of material into the lungs. Close monitoring of fluid and electrolyte balance is mandatory in view of the profuse offensive diarrhoea that most patients develop. Maintenance of nutrition, physiotherapy, prevention of bed sores and other routine measures to minimise discomfort during ventilatory care are necessary. Recovery from the intermediate syndrome is normally complete and without any sequelae. The usefulness of oximes during the IMS remains uncertain. In animal experiments, very early administration of oximes has prevented the occurrence of myopathy. There are reports from developed countries where administration of oximes at recommended doses and within 2 hours of ingestion of OP insecticide did not prevent the onset of the IMS. Controlled randomised clinical studies are necessary to evaluate the efficacy of oximes in combating the IMS. Electrophysiological studies following OP poisoning have revealed three characteristic phenomena: (i) repetitive firing following a single stimulus; (ii) gradual reduction in twitch height or compound muscle action potential followed by an increase with repetitive stimulation (the 'decrement-increment response'); and (iii) continued reduction in twitch height or compound muscle action potential with repetitive simulation ('decrementing response'). Of these, the decrementing response is the most frequent finding during the IMS, whilst repetitive firing is observed during the acute cholinergic syndrome. The distribution of the weakness in human cases of the IMS, in general, parallels the distribution of the myopathy observed in a number of studies in experimental animals. This has led to speculation that myopathy is involved in the causation of the IMS. However, while myopathy and the IMS have a common origin in acetylcholine accumulation, they are not causally related to one another.

Effects of body position on the ventilatory response following an impulse exercise in humans.

PubMed

Haouzi, Philippe; Chenuel, Bruno; Chalon, Bernard

2002-04-01

The aim of this study was to identify some of the mechanisms that could be involved in blunted ventilatory response (VE) to exercise in the supine (S) position. The contribution of the recruitment of different muscle groups, the activity of the cardiac mechanoreceptors, the level of arterial baroreceptor stimulation, and the hemodynamic effects of gravity on the exercising muscles was analyzed during upright (U) and S exercise. Delayed rise in VE and pulmonary gas exchange following an impulselike change in work rate (supramaximal leg cycling at 240 W for 12 s) was measured in seven healthy subjects and six heart transplant patients both in U and S positions. This approach allows study of the relationship between the rise in VE and O2 uptake (VO2) without the confounding effects of contractions of different muscle groups. These responses were compared with those triggered by an impulselike change in work rate produced by the arms, which were positioned at the same level as the heart in S and U positions to separate effects of gravity on postexercising muscles from those on the rest of the body. Despite superimposable VO2 and CO2 output responses, the delayed VE response after leg exercise was significantly lower in the S posture than in the U position for each control subject and cardiac-transplant patient (-2.58 +/- 0.44 l and -3.52 +/- 1.11 l/min, respectively). In contrast, when impulse exercise was performed with the arms, reduction of ventilatory response in the S posture reached, at best, one-third of the deficit after leg exercise and was always associated with a reduction in VO2 of a similar magnitude. We concluded that reduction in VE response to exercise in the S position is independent of the types (groups) of muscles recruited and is not critically dependent on afferent signals originating from the heart but seems to rely on some of the effects of gravity on postexercising muscles.

Influence of myocardial oxygen demand on the coronary vascular response to arterial blood gas changes in humans.

PubMed

Vermeulen, Tyler Dennis; Boulet, Lindsey M; Stembridge, Mike; Williams, Alexandra Mackenzie; Anholm, James D; Subedi, Prajan; Gasho, Chris; Ainslie, Philip N; Feigl, Eric O; Foster, Glen Edward

2018-03-30

It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial PO 2 and PCO 2 or if coronary vascular responses are the result of concomitant increases in myocardial O 2 consumption/demand (MVO 2 ). We hypothesized that the coronary vascular response to PO 2 and PCO 2 would be attenuated in healthy men when MVO 2 was attenuated with β 1 -adrenergic receptor blockade. Healthy men (n=11; age: 25 {plus minus} 1 years) received intravenous esmolol (β 1 -adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized, crossover study, and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and following 5-min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LAD V ; Doppler echocardiography), heart rate and arterial blood pressure. LAD V values at the end of each hypoxic condition were compared between esmolol and placebo. Rate pressure product (RPP) and left-ventricular mechanical energy (ME LV ) were calculated as indices of MVO 2 . All gas manipulations augmented RPP, ME LV , and LAD V but only RPP and ME LV were attenuated (4-18%) following β 1 -adrenergic receptor blockade (P<0.05). Despite attenuated RPP and MELV responses, β 1 -adrenergic receptor blockade did not attenuate the mean LADV vasodilatory response when compared to placebo during poikilocapnic hypoxia (29.4{plus minus}2.2 vs. 27.3{plus minus}1.6 cm/s) and isocapnic hypoxia (29.5{plus minus}1.5 vs. 30.3{plus minus}2.2 cm/s). Hypercapnic hypoxia elicited a feed-forward coronary dilation that was blocked by β 1 -adrenergic receptor blockade. These results indicate a direct influence of arterial PO 2 on coronary vascular regulation that is independent of MVO 2 .

Muscimol microinjected in the arcuate nucleus affects metabolism, body temperature & ventilation.

PubMed

Schlenker, Evelyn H

2016-06-15

Effects of microinjection of 2 doses of γ-aminobutyric acid (GABA)A receptor agonist, muscimol (M), into the hypothalamic arcuate nucleus on oxygen consumption and control of ventilation over time and body temperature (BT) at the end of the experiment were compared in adult male and female rats. Relative to cerebrospinal fluid (CSF, 0 nmol), BT was decreased only in male rats with both doses of M, while in female rats, the 5 nmol dose depressed oxygen consumption. Ventilation was depressed by 5 nmol M in male and 10 nmol M in female rats by decreasing tidal volume. M did not affect the ventilatory response of male or female rats to hypoxia, whereas in females 5 and 10 nmol M and in males 10 nmol M depressed the ventilatory response to hypercapnia. Thus, in rats GABAA receptors in the arcuate nucleus modulate BT, oxygen consumption, and ventilation in air and in response to hypercapnia in a sexually dimorphic manner. Copyright © 2016 Elsevier B.V. All rights reserved.

Body temperature depression and peripheral heat loss accompany the metabolic and ventilatory responses to hypoxia in low and high altitude birds.

PubMed

Scott, Graham R; Cadena, Viviana; Tattersall, Glenn J; Milsom, William K

2008-04-01

The objectives of this study were to compare the thermoregulatory, metabolic and ventilatory responses to hypoxia of the high altitude bar-headed goose with low altitude waterfowl. All birds were found to reduce body temperature (T(b)) during hypoxia, by up to 1-1.5 degrees C in severe hypoxia. During prolonged hypoxia, T(b) stabilized at a new lower temperature. A regulated increase in heat loss contributed to T(b) depression as reflected by increases in bill surface temperatures (up to 5 degrees C) during hypoxia. Bill warming required peripheral chemoreceptor inputs, since vagotomy abolished this response to hypoxia. T(b) depression could still occur without bill warming, however, because vagotomized birds reduced T(b) as much as intact birds. Compared to both greylag geese and pekin ducks, bar-headed geese required more severe hypoxia to initiate T(b) depression and heat loss from the bill. However, when T(b) depression or bill warming were expressed relative to arterial O(2) concentration (rather than inspired O(2)) all species were similar; this suggests that enhanced O(2) loading, rather than differences in thermoregulatory control centres, reduces T(b) depression during hypoxia in bar-headed geese. Correspondingly, bar-headed geese maintained higher rates of metabolism during severe hypoxia (7% inspired O(2)), but this was only partly due to differences in T(b). Time domains of the hypoxic ventilatory response also appeared to differ between bar-headed geese and low altitude species. Overall, our results suggest that birds can adjust peripheral heat dissipation to facilitate T(b) depression during hypoxia, and that bar-headed geese minimize T(b) and metabolic depression as a result of evolutionary adaptations that enhance O(2) transport.

Peripheral muscle ergoreceptors and ventilatory response during exercise recovery in heart failure.

PubMed

Francis, N; Cohen-Solal, A; Logeart, D

1999-03-01

Recent studies have suggested that the increased ventilatory response during exercise in patients with chronic heart failure was related to the activation of muscle metaboreceptors. To address this issue, 23 patients with heart failure and 7 normal subjects performed arm and leg bicycle exercises with and without cuff inflation around the arms or the thighs during recovery. Obstruction slightly reduced ventilation and gas exchange variables at recovery but did not change the kinetics of recovery of these parameters compared with nonobstructed recovery: half-time of ventilation recovery was 175 +/- 54 to 176 +/- 40 s in patients and 155 +/- 66 to 127 +/- 13 s in controls (P < 0.05, patients vs. controls, not significant within each group from baseline to obstructed recovery). We conclude that muscle metaboreceptor activation does not seem to play a role in the exertion hyperventilation of patients with heart failure.

Antioxidants prevent depression of the acute hypoxic ventilatory response by subanaesthetic halothane in men

PubMed Central

Teppema, Luc J; Nieuwenhuijs, Diederik; Sarton, Elise; Romberg, Raymonda; Olievier, Cees N; Ward, Denham S; Dahan, Albert

2002-01-01

We studied the effect of the antioxidants (AOX) ascorbic acid (2 g, I.V.) and α-tocopherol (200 mg, P.O.) on the depressant effect of subanaesthetic doses of halothane (0.11 % end-tidal concentration) on the acute isocapnic hypoxic ventilatory response (AHR), i.e. the ventilatory response upon inhalation of a hypoxic gas mixture for 3 min (leading to a haemoglobin saturation of 82 ± 1.8 %) in healthy male volunteers. In the first set of protocols, two groups of eight subjects each underwent a control hypoxic study, a halothane hypoxic study and finally a halothane hypoxic study after pretreatment with AOX (study 1) or placebo (study 2). Halothane reduced the AHR by more than 50 %, from 0.79 ± 0.31 to 0.36 ± 0.14 l min−1 %−1 in study 1 and from 0.79 ± 0.40 to 0.36 ± 0.19 l min−1 %−1 in study 2, P < 0.01 for both. Pretreatment with AOX prevented this depressant effect of halothane in the subjects of study 1 (AHR returning to 0.77 ± 0.32 l min−1 %−1, n.s. from control), whereas placebo (study 2) had no effect (AHR remaining depressed at 0.36 ± 0.27 l min−1 %−1, P < 0.01 from control). In a second set of protocols, two separate groups of eight subjects each underwent a control hypoxic study, a sham halothane hypoxic study and finally a sham halothane hypoxic study after pretreatment with AOX (study 3) or placebo (study 4). In studies 3 and 4, sham halothane did not modify the control hypoxic response, nor did AOX (study 3) or placebo (study 4). The 95 % confidence intervals for the ratio of hypoxic sensitivities, (AOX + halothane):halothane in study 1 and (AOX - sham halothane):sham halothane in study 3, were [1.7, 2.6] and [1.0, 1.2], respectively. Because the antioxidants prevented the reduction of the acute hypoxic response by halothane, we suggest that this depressant effect may be caused by reactive species produced by a reductive metabolism of halothane during hypoxia or that a change in redox state of carotid body cells by the antioxidants prevented or changed the binding of halothane to its effect site. Our findings may also suggest that reactive species have an inhibiting effect on the acute hypoxic ventilatory response. PMID:12411535

Ventilatory Responses to Exercise While Eliciting the Relaxation Response,

DTIC Science & Technology

1982-04-16

Kent B. Pandolf, Bruce Cadarette, Leslie Levine, Ralph F. Goldman, and Herbert Benson. From the Division of Behavioral Medicine, Department of...been observed with the elicitation of the relaxation response at rest differ from those that occur during sleep or hypnosis (14). The relaxation response...alterations which were observed in our experimental group during the intervention period were not similar to those found with combined hypnosis and

Dynamic Characteristics of Ventilatory and Gas Exchange during Sinusoidal Walking in Humans.

PubMed

Fukuoka, Yoshiyuki; Iihoshi, Masaaki; Nazunin, Juhelee Tuba; Abe, Daijiro; Fukuba, Yoshiyuki

2017-01-01

Our present study investigated whether the ventilatory and gas exchange responses show different dynamics in response to sinusoidal change in cycle work rate or walking speed even if the metabolic demand was equivalent in both types of exercise. Locomotive parameters (stride length and step frequency), breath-by-breath ventilation (V̇E) and gas exchange (CO2 output (V̇CO2) and O2 uptake (V̇O2)) responses were measured in 10 healthy young participants. The speed of the treadmill was sinusoidally changed between 3 km·h-1 and 6 km·h-1 with various periods (from 10 to 1 min). The amplitude of locomotive parameters against sinusoidal variation showed a constant gain with a small phase shift, being independent of the oscillation periods. In marked contrast, when the periods of the speed oscillations were shortened, the amplitude of V̇E decreased sharply whereas the phase shift of V̇E increased. In comparing walking and cycling at the equivalent metabolic demand, the amplitude of V̇E during sinusoidal walking (SW) was significantly greater than that during sinusoidal cycling (SC), and the phase shift became smaller. The steeper slope of linear regression for the V̇E amplitude ratio to V̇CO2 amplitude ratio was observed during SW than SC. These findings suggested that the greater amplitude and smaller phase shift of ventilatory dynamics were not equivalent between SW and SC even if the metabolic demand was equivalent between both exercises. Such phenomenon would be derived from central command in proportion to locomotor muscle recruitment (feedforward) and muscle afferent feedback.

Unconstrained and Noninvasive Measurement of Swimming Behavior of Small Fish Based on Ventilatory Signals

NASA Astrophysics Data System (ADS)

Kitayama, Shigehisa; Soh, Zu; Hirano, Akira; Tsuji, Toshio; Takiguchi, Noboru; Ohtake, Hisao

Ventilatory signal is a kind of bioelectric signals reflecting the ventilatory conditions of fish, and has received recent attention as an indicator for assessment of water quality, since breathing is adjusted by the respiratory center according to changes in the underwater environment surrounding the fish. The signals are thus beginning to be used in bioassay systems for water examination. Other than ventilatory conditions, swimming behavior also contains important information for water examination. The conventional bioassay systems, however, only measure either ventilatory signals or swimming behavior. This paper proposes a new unconstrained and noninvasive measurement method that is capable of conducting ventilatory signal measurement and behavioral analysis of fish at the same time. The proposed method estimates the position and the velocity of a fish in free-swimming conditions using power spectrum distribution of measured ventilatory signals from multiple electrodes. This allowed the system to avoid using a camera system which requires light sources. In order to validate estimation accuracy, the position and the velocity estimated by the proposed method were compared to those obtained from video analysis. The results confirmed that the estimated error of the fish positions was within the size of fish, and the correlation coefficient between the velocities was 0.906. The proposed method thus not only can measure the ventilatory signals, but also performs behavioral analysis as accurate as using a video camera.

Response of Preterm Infants to 2 Noninvasive Ventilatory Support Systems: Nasal CPAP and Nasal Intermittent Positive-Pressure Ventilation.

PubMed

Silveira, Carmen Salum Thomé; Leonardi, Kamila Maia; Melo, Ana Paula Carvalho Freire; Zaia, José Eduardo; Brunherotti, Marisa Afonso Andrade

2015-12-01

Noninvasive ventilation (NIV) in preterm infants is currently applied using intermittent positive pressure (2 positive-pressure levels) or in a conventional manner (one pressure level). However, there are no studies in the literature comparing the chances of failure of these NIV methods. The aim of this study was to evaluate the occurrence of failure of 2 noninvasive ventilatory support systems in preterm neonates over a period of 48 h. A randomized, prospective, clinical study was conducted on 80 newborns (gestational age < 37 weeks, birthweight < 2,500 g). The infants were randomized into 2 groups: 40 infants were treated with nasal CPAP and 40 infants with nasal intermittent positive-pressure ventilation (NIPPV). The occurrence of apnea, progression of respiratory distress, nose bleeding, and agitation was defined as ventilation failure. The need for intubation and re-intubation after failure was also observed. There were no significant differences in birth characteristics between groups. Ventilatory support failure was observed in 25 (62.5%) newborns treated with nasal CPAP and in 12 (30%) newborns treated with NIPPV, indicating an association between NIV failure and the absence of intermittent positive pressure (odds ratio [OR] 1.22, P < .05). Apnea (32.5%) was the main reason for nasal CPAP failure. After failure, 25% (OR 0.33) of the newborns receiving nasal CPAP and 12.5% (OR 0.14) receiving NIPPV required invasive mechanical ventilation. Ventilatory support failure was significantly more frequent when nasal CPAP was used. Copyright © 2015 by Daedalus Enterprises.

Substance P-induced respiratory excitation is blunted by delta-receptor specific opioids in the rat medulla oblongata.

PubMed

Chen, Z; Hedner, J; Hedner, T

1996-06-01

The effects of substance P (SP) and the naturally occurring met-enkephalin and the synthetic mu-specific opioid agonist, DAGO (Tyr-D-Ala-Gly-N-Methy-Phe-Gly-ol) and the delta-specific opioid agonist DADL (Tyr-D-Ala-Gly-Phe-D-Leu) on basal ventilation were investigated in halothane-anaesthetized rats. Local injections of SP (0.75-1.5 nmol) in the ventrolateral medulla oblongata (VLM), e.g. nucleus paragigantocellularis, and nucleus reticularis lateralis increased ventilation because of an elevation of tidal volume. Met-enkephalin induced a short-lasting ventilatory depression mainly because of a depression of tidal volume. Activation of delta- and mu-opioid receptors in the VLM by local application of DADL and DAGO, respectively, induced ventilatory depression, which was later in onset and more long-lasting. Local administration of met-enkephalin into the VLM also produced a long-lasting inhibition of the SP-induced ventilatory excitation. A similar blockade of the SP-induced excitatory ventilatory response could be elicited by DADL but not by DAGO. This antagonistic effect was attenuated by local application of the delta-opioid receptor antagonist ICI 154. 129. We conclude that the naturally occurring met-enkephalin as well as synthetic mu- and delta-specific enkephalin analogues (DAGO and DADL, respectively) in VLM depress basal ventilation by an effect on inspiratory drive. There is a functional antagonism between activation of delta-opioid receptors and SP receptors into the VLM in respect to respiratory regulation.

Acute Toxicity, Respiratory Reaction, and Sensitivity of Three Cyprinid Fish Species Caused by Exposure to Four Heavy Metals

PubMed Central

Wang, Hongjun; Liang, Youguang; Li, Sixin; Chang, Jianbo

2013-01-01

Using 3 cyprinid fish species zebra fish, rare minnow, and juvenile grass carp, we conducted assays of lethal reaction and ventilatory response to analyze sensitivity of the fish to 4 heavy metals. Our results showed that the 96 h LC50 of Hg2+ to zebra fish, juvenile grass carp, and rare minnow were 0.14 mg L−1, 0.23 mg L−1, and 0.10 mg L−1, respectively; of Cu2+0.17 mg L−1, 0.09 mg L−1, and 0.12 mg L−1 respectively; of Cd2+6.5 mg L−1, 18.47 mg L−1, 5.36 mg L−1, respectively; and of Zn2+44.48 mg L−1, 31.37 mg L−1, and 12.74 mg L−1, respectively. Under a 1-h exposure, the ventilatory response to the different heavy metals varied. Ventilatory frequency (Vf) and amplitude (Va) increased in zebra fish, juvenile grass carp, and rare minnows exposed to Hg2+ and Cu2+ (P<0.05), and the Vf and Va of the 3 species rose initially and then declined when exposed to Cd2+. Zn2+ had markedly different toxic effects than the other heavy metals, whose Vf and Va gradually decreased with increasing exposure concentration (P<0.05). The rare minnow was the most highly susceptible of the 3 fish species to the heavy metals, with threshold effect concentrations (TEC) of 0.019 mg L−1, 0.046 mg L−1, 2.142 mg L−1, and 0.633 mg L−1 for Hg2+, Cu2+, Cd2+, and Zn2+, respectively. Therefore, it is feasible to use ventilatory parameters as a biomarker for evaluating the pollution toxicity of metals and to recognize early warning signs by using rare minnows as a sensor. PMID:23755209

Flexible bronchoscopy during non-invasive positive pressure mechanical ventilation: are two better than one?

PubMed

Scala, Raffaele

2016-09-01

Flexible bronchoscopy (FBO) and non-invasive positive pressure ventilation (NIPPV) are largely applied in respiratory and general intensive care units. FBO plays a crucial role for the diagnosis of lung infiltrates of unknown origin and for the treatment of airways obstruction due to bronchial mucous plugging and hemoptysis in critical patients. NIPPV is the first-choice ventilatory strategy for acute respiratory failure (ARF) of different causes as it could be used as prevention or as alternative to the conventional mechanical ventilation (CMV) via endotracheal intubation (ETI). Some clinical scenarios represent contraindications for these techniques such as severe ARF in spontaneous breathing patients for FBO and accumulated tracheo-bronchial secretions in patients with depressed cough for NIPPV. In these contexts, the decision of performing ETI should carefully consider the risk of CMV-correlated complications. An increasing amount of published data suggested the use of FBO during NIPPV in ARF in order to avoid/reduce the need of ETI. Despite a strong rationale for the combined use of the two techniques, there is not still enough evidence for a large-scale application of this strategy in all different clinical scenarios. The majority of the available data are in favor of the "help" given by NIPPV to diagnostic FBO in high-risk spontaneously breathing patients with severe hypoxemia. Preliminary findings report the successful "help" given by early FBO to NIPPV in patients with hypoxemic-hypercapnic ARF who are likely to fail because of hypersecretion. Synergy of FBO and NIPPV application is emerging also to perform ETI in challenging situations, such as predicted difficult laringoscopy and NPPV failure in severely hypoxemic patients. This combined approach should be performed only in centers showing a wide experience with both NIPPV and FBO, where close monitoring and ETI facilities are promptly available.

Clinical impact of leak compensation during non-invasive ventilation.

PubMed

Storre, Jan Hendrik; Bohm, Philipp; Dreher, Michael; Windisch, Wolfram

2009-10-01

This study aimed to assess the impact of leak compensation capabilities during pressure- and volume-limited non-invasive positive-pressure ventilation (NPPV) in COPD patients. Fourteen patients with stable hypercapnic COPD who were receiving long-term NPPV were included in the study. For both modes of NPPV, a full face mask and an artificial leak in the ventilatory circuit were used at three different settings, and applied during daytime NPPV, either without leakage (setting I), with leakage during inspiration only (setting II), and with leakage during inspiration and expiration (setting III). Ventilation pattern was pneumotachy-graphically recorded. NPPV was feasible with negligible leak volumes, indicating optimal mask fitting during the daytime (setting I). In the presence of leakage (settings II and III), the attempt to compensate for leak was only evident during pressure-limited NPPV, since inspiratory volumes delivered by the ventilator increased from 726+/-129 (setting I) to 1104+/-164 (setting II), and to 1257+/-166 (setting III) ml during pressure-limited NPPV, respectively (all p<0.001); however, they remained stable during volume-limited NPPV. Leak compensation resulted in a decrease in leakage-induced dyspnea. However, 83%/87% (setting II/III) of the additionally-delivered inspiratory volume during pressure-limited NPPV was also lost via leakage. Expiratory volume was higher in setting II compared to setting III (both p<0.001), indicating the presence of significant expiratory leakage. The attempt at leak compensation largely feeds the leakage itself and only results in a marginal increase of tidal volume. However, pressure-limited--but not volume-limited--NPPV results in a clinically-important leak compensation in vivo. www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html Identifier: UKF001272.

"Optimal" application of ventilatory assist in Cheyne-Stokes respiration: a simulation study.

PubMed

Khoo, M C; Benser, M E

2005-01-01

Although a variety of ventilator therapies have been employed to treat Cheyne-Stokes respiration (CSR), these modalities do not completely eliminate CSR. As well, most current strategies require that ventilatory assist be provided continuously. We used a computer model of the respiratory control system to determine whether a ventilatory assist strategy could be found that would substantially reduce the severity of CSR while minimizing the application of positive airway pressure. We assessed the effects of different levels of ventilatory assist applied during breaths that fell below selected hypopneic thresholds. These could be applied during the descending, ascending, or both phases of the CSR cycle. We found that ventilatory augmentation equal to 30-40% of eupneic drive, applied whenever ventilation fell below 70% of the eupneic level during the ascending or descending-and-ascending phases of CSR led to the greatest regularization of breathing with minimal ventilator intervention. Application of ventilatory assist during the descending phase produced little effect.

Whole Body Plethysmography Reveals Differential Ventilatory Responses to Ozone in Rat Models of Cardiovascular Disease

EPA Science Inventory

Increasingly, urban air pollution is recognized as an important determinant of cardiovascular disease. Host susceptibility to air pollution can vary due to genetic predisposition and underlying disease. To elucidate key factors of host ...

Combined effects of mild-to-moderate obesity and asthma on physiological and sensory responses to exercise.

PubMed

Cortés-Télles, Arturo; Torre-Bouscoulet, Luis; Silva-Cerón, Monica; Mejía-Alfaro, Roberto; Syed, Nafeez; Zavorsky, Gerald S; Guenette, Jordan A

2015-11-01

Despite the close link between asthma and obesity, there are no studies that have evaluated the sensory and physiological responses to exercise in obese asthmatics. We recently demonstrated that normal weight asthmatics with well controlled disease have preserved cardiorespiratory and sensory responses to exercise relative to non-asthmatic controls. However, these similarities may not hold true in patients with combined obesity and asthma. Accordingly, we sought to determine if combined asthma and obesity was associated with deleterious effects on cardiorespiratory fitness, exercise performance, dyspnoea, and physiological responses to exercise. Fourteen well-controlled obese asthmatics and fourteen age-matched normal weight asthmatics performed routine spirometry and underwent an incremental cardiopulmonary cycle test to assess the ventilatory, pulmonary gas exchange, cardiovascular, and sensory responses to exercise. Groups were well matched for age, height, spirometry, and asthma control. Obese asthmatics had a significantly greater body mass index (33 ± 3 vs. 23 ± 1 kg/m(2), p < 0.001) and lower self-reported activity levels by 47 % relative to normal weight asthmatics (p < 0.05). Obese asthmatics had a significantly lower maximal oxygen uptake (VO(2)) (82 ± 14 vs. 92 ± 10 %predicted) and work rate (75 ± 8 vs. 89 ± 13 %predicted) relative to normal weight asthmatics (p < 0.05). The anaerobic threshold occurred at a lower VO(2) in obese asthmatics vs. normal weight asthmatics (54 ± 15 vs. 66 ± 16 %predicted, p < 0.05). Ventilatory responses were superimposed throughout exercise with no evidence of a ventilatory limitation in either group. Cardiovascular responses were normal in both groups. Dyspnoea responses were similar but the obese asthmatics experienced greater leg fatigue ratings at submaximal work rates. In conclusion, obese individuals with well controlled asthma have reduced cardiorespiratory fitness and greater leg fatigue ratings relative to normal weight asthmatics. The relatively reduced cardiorespiratory fitness and exercise performance in obese compared to normal weight asthmatics is most likely driven by their more sedentary lifestyle and resultant deconditioning rather than due to respiratory factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phase I/II Trial of Adeno-Associated Virus–Mediated Alpha-Glucosidase Gene Therapy to the Diaphragm for Chronic Respiratory Failure in Pompe Disease: Initial Safety and Ventilatory Outcomes

PubMed Central

Smith, Barbara K.; Collins, Shelley W.; Conlon, Thomas J.; Mah, Cathryn S.; Lawson, Lee Ann; Martin, Anatole D.; Fuller, David D.; Cleaver, Brian D.; Clément, Nathalie; Phillips, Dawn; Islam, Saleem; Dobjia, Nicole

2013-01-01

Abstract Pompe disease is an inherited neuromuscular disease caused by deficiency of lysosomal acid alpha-glucosidase (GAA) leading to glycogen accumulation in muscle and motoneurons. Cardiopulmonary failure in infancy leads to early mortality, and GAA enzyme replacement therapy (ERT) results in improved survival, reduction of cardiac hypertrophy, and developmental gains. However, many children have progressive ventilatory insufficiency and need additional support. Preclinical work shows that gene transfer restores phrenic neural activity and corrects ventilatory deficits. Here we present 180-day safety and ventilatory outcomes for five ventilator-dependent children in a phase I/II clinical trial of AAV-mediated GAA gene therapy (rAAV1-hGAA) following intradiaphragmatic delivery. We assessed whether rAAV1-hGAA results in acceptable safety outcomes and detectable functional changes, using general safety measures, immunological studies, and pulmonary functional testing. All subjects required chronic, full-time mechanical ventilation because of respiratory failure that was unresponsive to both ERT and preoperative muscle-conditioning exercises. After receiving a dose of either 1×1012 vg (n=3) or 5×1012 vg (n=2) of rAAV1-hGAA, the subjects' unassisted tidal volume was significantly larger (median [interquartile range] 28.8% increase [15.2–35.2], p<0.05). Further, most patients tolerated appreciably longer periods of unassisted breathing (425% increase [103–851], p=0.08). Gene transfer did not improve maximal inspiratory pressure. Expected levels of circulating antibodies and no T-cell-mediated immune responses to the vector (capsids) were observed. One subject demonstrated a slight increase in anti-GAA antibody that was not considered clinically significant. These results indicate that rAAV1-hGAA was safe and may lead to modest improvements in volitional ventilatory performance measures. Evaluation of the next five patients will determine whether earlier intervention can further enhance the functional benefit. PMID:23570273

Liquid extracorporeal carbon dioxide removal: use of THAM (tris-hydroxymethyl aminomethane) coupled to hemofiltration to control hypercapnic acidosis in a porcine model of protective mechanical ventilation

PubMed Central

Tapia, Pablo; Lillo, Felipe; Soto, Dagoberto; Escobar, Leslie; Simon, Felipe; Hernández, Karina; Alegría, Leyla; Bruhn, Alejandro

2016-01-01

A promising approach to facilitate protective mechanical ventilation is the use of extracorporeal CO2 removal techniques. Several strategies based on membrane gas exchangers have been developed. However, these techniques are still poorly available. The goal of this study was to assess the efficacy and safety of THAM infusion coupled to hemofiltration for the management of hypercapnic acidosis. A severe respiratory acidosis was induced in seven anesthetized pigs. Five of them were treated with THAM 8-mmol·kg-1·h-1 coupled to hemofiltration (THAM+HF group) at 100 mL·kg-1·h-1. After 18-hours of treatment the THAM infusion was stopped but hemofiltration was kept on until 24-hours. The 2 other animals were treated with THAM but without hemofiltration. After 1-hour of treatment in THAM+HF, PaCO2 rapidly decreased from a median of 89.0 (IQR) (80.0, 98.0) to 71.3 (65.8, 82.0) mmHg (P<0.05), while pH increased from 7.12 (7.01, 7.15) to 7.29 (7.27, 7.30) (P<0.05). Thereafter PaCO2 remained stable between 60-70 mmHg, while pH increased above 7.4. After stopping THAM at 18 hours of treatment a profound rebound effect was observed with severe hypercapnic acidosis. The most important side effect we observed was hyperosmolality, which reached a maximum of 330 (328, 332) mOsm·kg H2O-1 at T18. The animals treated only with THAM developed severe hypercapnia, despite the fact that pH returned to normal values, and died after 12 hours. Control-group had an uneven evolution until the end of the experiment. A combined treatment with THAM coupled to hemofiltration may be an effective treatment to control severe hypercapnic acidosis. PMID:27648139

20 CFR 410.430 - Ventilatory studies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Ventilatory studies. 410.430 Section 410.430... studies. Spirometric tests to measure ventilatory function must be expressed in liters or liters per... least 20 millimeters (mm.) per second. The height of the individual must be recorded. Studies should not...

20 CFR 410.430 - Ventilatory studies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Ventilatory studies. 410.430 Section 410.430... studies. Spirometric tests to measure ventilatory function must be expressed in liters or liters per... least 20 millimeters (mm.) per second. The height of the individual must be recorded. Studies should not...

OBESITY: CHALLENGES TO VENTILATORY CONTROL DURING EXERCISE A BRIEF REVIEW

PubMed Central

Babb, Tony G.

2013-01-01

Obesity is a national health issue in the US. Among the many physiological changes induced by obesity, it also presents a unique challenge to ventilatory control during exercise due to increased metabolic demand of moving larger limbs, increased work of breathing due to extra weight on the chest wall, and changes in breathing mechanics. These challenges to ventilatory control in obesity can be inconspicuous or overt among obese adults but for the most part adaptation of ventilatory control during exercise in obesity appears remarkably unnoticed in the majority of obese people. In this brief review, the changes to ventilatory control required for maintaining normal ventilation during exercise will be examined, especially the interaction between respiratory neural drive and ventilation. Also, gaps in our current knowledge will be discussed. PMID:23707540

Respiratory symptoms and ventilatory performance in workers exposed to grain and grain based food dusts.

PubMed

Deacon, S P; Paddle, G M

1998-05-01

A health surveillance study of male grain food manufacturing workers used a respiratory health questionnaire and spirometry to assess the prevalence of work-related respiratory symptoms and impaired ventilatory performance. The prevalence of cough, breathlessness, wheeze and chest tightness was between 8-13% but was 20% for rhinitis. Rhinitis was the most common symptom with 37% of those reporting rhinitis describing this as work-related. A case-control analysis of workers reporting rhinitis did not identify any specific occupational activities associated with increased risk of rhinitis. Smoking habit and all respiratory symptoms apart from rhinitis had a significant effect upon ventilatory performance. Occupational exposure to raw grains, flour, ingredients and finished food was categorized as high, medium or low in either continuous or intermediate patterns. Multiple regression analysis confirmed the effects of height, age and smoking upon ventilatory performance. However, occupational exposure to grain, flour, food ingredients and cooked food dusts had no effect upon ventilatory performance. It is concluded that smoking habit is the major determinant of respiratory symptoms and impaired ventilatory function. The excess complaints of rhinitis warrant further study but it would appear that the current occupational exposure limits for grain, flour, food ingredients and cooked food dusts are adequate to protect workers against impairment of ventilatory performance.

Effects of adrenergic stimulation on ventilation in man

PubMed Central

Heistad, Donald D.; Wheeler, Robert C.; Mark, Allyn L.; Schmid, Phillip G.; Abboud, Francois M.

1972-01-01

The mechanism by which catecholamines affect ventilation in man is not known. Ventilatory responses to catecholamines were observed in normal subjects before and after adrenergic receptor blockade. Intravenous infusions of norepinephrine and isoproterenol caused significant increases in minute volume and decreases in end-tidal PCo2 which were blocked by the administration of propranolol, a beta adrenergic receptor blocker. The hyperventilatory response to hypoxia was not altered by propranolol. Intravenous infusion of phenylephrine caused a small but significant decrease in minute volume which was antagonized by phentolamine, an alpha adrenergic receptor blocker. Angiotensin, a nonadrenergic pressor agent, also decreased minute volume significantly. 100% oxygen was administered to suppress arterial chemoreceptors. Increases in minute volume and decreases in arterial PCo2 in response to norepinephrine and isoproterenol were blocked by breathing 100% oxygen. The decrease in minute volume during phenylephrine was not altered by 100% oxygen. The results indicate that: (a) beta adrenergic receptors mediate the hyperventilatory response to norepinephrine and isoproterenol but not to hypoxia. (b) the pressor agents phenylephrine and angiotensin decrease ventilation, and (c) suppression of chemoreceptors blocks the ventilatory response to norepinephrine and isoproterenol but not to phenylephrine. Implications concerning the interaction of adrenergic receptors and chemoreceptors with respect to the hyperventilatory response to catecholamines are discussed. PMID:4336940

Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia.

PubMed

Lumbroso, Delphine; Joseph, Vincent

2009-08-01

We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O(2); nHx group) in a sealed chamber, or to normoxia (21% O(2); nNx group) from the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 wk to 10% O(2). Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit, and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, VE/VCO(2)) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern and elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats, indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude.

Efficacy of high-flow oxygen by nasal cannula with active humidification in a patient with acute respiratory failure of neuromuscular origin.

PubMed

Díaz-Lobato, Salvador; Folgado, Miguel Angel; Chapa, Angel; Mayoralas Alises, Sagrario

2013-12-01

The treatment of choice for patients with respiratory failure of neuromuscular origin, especially in patients with hypercapnic respiratory acidosis, is noninvasive ventilation (NIV). Endotracheal intubation and invasive ventilation are indicated for patients with severe respiratory compromise or failure of NIV. In recent years, high-flow oxygen therapy and active humidification devices have been introduced, and emerging evidence suggests that high-flow oxygen may be effective in various clinical settings, such as acute respiratory failure, after cardiac surgery, during sedation and analgesia, in acute heart failure, in hypoxemic respiratory distress, in do-not-intubate patients, in patients with chronic cough and copious secretions, pulmonary fibrosis, or cancer, in critical areas and the emergency department. We report on a patient with amyotrophic lateral sclerosis who arrived at the emergency department with acute hypercapnic respiratory failure. She did not tolerate NIV and refused intubation, but was treated successfully with heated, humidified oxygen via high-flow nasal cannula. Arterial blood analysis after an hour on high-flow nasal cannula showed improved pH, P(aCO2), and awareness. The respiratory acidosis was corrected, and she was discharged after 5 days of hospitalization. Her response to high-flow nasal cannula was similar to that expected with NIV. We discuss the mechanisms of action of heated, humidified high-flow oxygen therapy.

Ventilatory Responses During Submaximal Exercise in Children With Prader-Willi Syndrome.

PubMed

Hyde, Adam M; McMurray, Robert G; Chavoya, Frank A; Rubin, Daniela A

2018-02-27

Prader-Willi syndrome (PWS) is a genetic neurobehavioral disorder presenting hypothalamic dysfunction and adiposity. At rest, PWS exhibits hypoventilation with hypercapnia. We characterized ventilatory responses in children with PWS during exercise. Participants were children aged 7-12 years with PWS (n = 8) and without PWS with normal weight (NW; n = 9, body mass index ≤ 85th percentile) or obesity (n = 9, body mass index ≥ 95th percentile). Participants completed three 5-minute ambulatory bouts at 3.2, 4.0, and 4.8 km/h. Oxygen uptake, carbon dioxide output, ventilation, breathing frequency, and tidal volume were recorded. PWS had slightly higher oxygen uptake (L/min) at 3.2 km/h [0.65 (0.46-1.01) vs 0.49 (0.34-0.83)] and at 4.8 km/h [0.89 (0.62-1.20) vs 0.63 (0.45-0.97)] than NW. PWS had higher ventilation (L/min) at 3.2 km/h [16.2 (13.0-26.5) vs 11.5 (8.4-17.5)], at 4.0 km/h [16.4 (13.9-27.9) vs 12.7 (10.3-19.5)], and at 4.8 km/h [19.7 (17.4-31.8) vs 15.2 (9.5-21.6)] than NW. PWS had greater breathing frequency (breaths/min) at 3.2 km/h [38 (29-53) vs 29 (22-35)], at 4.0 km/h [39 (29-58) vs 29 (23-39)], and at 4.8 km/h [39 (33-58) vs 32 (23-42)], but similar tidal volume and ventilation/carbon dioxide output to NW. PWS did not show impaired ventilatory responses to exercise. Hyperventilation in PWS may relate to excessive neural stimulation and metabolic cost.

Noninvasive ventilation in stable hypercapnic COPD: what is the evidence?

PubMed Central

Duiverman, Marieke L.

2018-01-01

Long-term noninvasive ventilation (NIV) to treat chronic hypercapnic respiratory failure is still controversial in severe chronic obstructive pulmonary disease (COPD) patients. However, with the introduction of high-intensity NIV, important benefits from this therapy have also been shown in COPD. In this review, the focus will be on the arguments for long-term NIV at home in patients with COPD. The rise of (high-intensity) NIV in COPD and the randomised controlled trials showing positive effects with this mode of ventilation will be discussed. Finally, the challenges that might be encountered (both in clinical practice and in research) in further optimising this therapy, monitoring and following patients, and selecting the patients who might benefit most will be reviewed. PMID:29637078

Guinea Pig as a Model to Study the Carotid Body Mediated Chronic Intermittent Hypoxia Effects.

PubMed

Docio, Inmaculada; Olea, Elena; Prieto-LLoret, Jesus; Gallego-Martin, Teresa; Obeso, Ana; Gomez-Niño, Angela; Rocher, Asuncion

2018-01-01

Clinical and experimental evidence indicates a positive correlation between chronic intermittent hypoxia (CIH), increased carotid body (CB) chemosensitivity, enhanced sympatho-respiratory coupling and arterial hypertension and cardiovascular disease. Several groups have reported that both the afferent and efferent arms of the CB chemo-reflex are enhanced in CIH animal models through the oscillatory CB activation by recurrent hypoxia/reoxygenation episodes. Accordingly, CB ablation or denervation results in the reduction of these effects. To date, no studies have determined the effects of CIH treatment in chemo-reflex sensitization in guinea pig, a rodent with a hypofunctional CB and lacking ventilatory responses to hypoxia. We hypothesized that the lack of CB hypoxia response in guinea pig would suppress chemo-reflex sensitization and thereby would attenuate or eliminate respiratory, sympathetic and cardiovascular effects of CIH treatment. The main purpose of this study was to assess if guinea pig CB undergoes overactivation by CIH and to correlate CIH effects on CB chemoreceptors with cardiovascular and respiratory responses to hypoxia. We measured CB secretory activity, ventilatory parameters, systemic arterial pressure and sympathetic activity, basal and in response to acute hypoxia in two groups of animals: control and 30 days CIH exposed male guinea pigs. Our results indicated that CIH guinea pig CB lacks activity elicited by acute hypoxia measured as catecholamine (CA) secretory response or intracellular calcium transients. Plethysmography data showed that only severe hypoxia (7% O 2 ) and hypercapnia (5% CO 2 ) induced a significant increased ventilatory response in CIH animals, together with higher oxygen consumption. Therefore, CIH exposure blunted hyperventilation to hypoxia and hypercapnia normalized to oxygen consumption. Increase in plasma CA and superior cervical ganglion CA content was found, implying a CIH induced sympathetic hyperactivity. CIH promoted cardiovascular adjustments by increasing heart rate and mean arterial blood pressure without cardiac ventricle hypertrophy. In conclusion, CIH does not sensitize CB chemoreceptor response to hypoxia but promotes cardiovascular adjustments probably not mediated by the CB. Guinea pigs could represent an interesting model to elucidate the mechanisms that underlie the long-term effects of CIH exposure to provide evidence for the role of the CB mediating pathological effects in sleep apnea diseases.

T3 supplementation affects ventilatory timing & glucose levels in type 2 diabetes mellitus model.

PubMed

Bollinger, Stephen S; Weltman, Nathen Y; Gerdes, A Martin; Schlenker, Evelyn H

2015-01-01

Type II diabetes mellitus (T2DM) can affect ventilation, metabolism, and fasting blood glucose levels. Hypothyroidism may be a comorbidity of T2DM. In this study T2DM was induced in 20 female Sprague Dawley rats using Streptozotocin (STZ) and Nicotinamide (N). One of experimental STZ/N groups (N=10 per group) was treated with a low dose of triiodothyronine (T3). Blood glucose levels, metabolism and ventilation (in air and in response to hypoxia) were measured in the 3 groups. STZ/N-treated rats increased fasting blood glucose compared to control rats eight days and 2 months post-STZ/N injections indicating stable induction of T2DM state. Treatments had no effects on ventilation, metabolism or body weight. After one month of T3 supplementation, there were no physiological indications of hyperthyroidism, but T3 supplementation altered ventilatory timing and decreased blood glucose levels compared to STZ/N rats. These results suggest that low levels of T3 supplementation could offer modest effects on blood glucose and ventilatory timing in this T2M model. Copyright © 2014 Elsevier B.V. All rights reserved.

Stress-induced thermotolerance of ventilatory motor pattern generation in the locust, Locusta migratoria.

PubMed

Newman, Amy E M; Foerster, Melody; Shoemaker, Kelly L; Robertson, R Meldrum

2003-11-01

Ventilation is a crucial motor activity that provides organisms with an adequate circulation of respiratory gases. For animals that exist in harsh environments, an important goal is to protect ventilation under extreme conditions. Heat shock, anoxia, and cold shock are environmental stresses that have previously been shown to trigger protective responses. We used the locust to examine stress-induced thermotolerance by monitoring the ability of the central nervous system to generate ventilatory motor patterns during a subsequent heat exposure. Preparations from pre-stressed animals had an increased incidence of motor pattern recovery following heat-induced failure, however, prior stress did not alter the characteristics of the ventilatory motor pattern. During constant heat exposure at sub-lethal temperatures, we observed a protective effect of heat shock pre-treatment. Serotonin application had similar effects on motor patterns when compared to prior heat shock. These studies are consistent with previous studies that indicate prior exposure to extreme temperatures and hypoxia can protect neural operation against high temperature stress. They further suggest that the protective mechanism is a time-dependent process best revealed during prolonged exposure to extreme temperatures and is mediated by a neuromodulator such as serotonin.

Cardiovascular and ventilatory responses to dorsal, facial, and whole-head water immersion in eupnea.

PubMed

Gagnon, Dominique D; Pretorius, Thea; McDonald, Gerren; Kenny, Glen P; Giesbrecht, Gordon G

2013-06-01

Facial cooling can regulate reflexes of the dive response whereas further body cooling generally induces the cold-shock response. We examined the cardiovascular and ventilatory parameters of these responses during 3-min immersions of the head dorsum, face, and whole head in 17 degrees C water while breathing was maintained. From a horizontal position, the head was inserted into a temperature controlled immersion tank in which the water level could be changed rapidly. On four occasions, either the head dorsum, face or whole head (prone and supine) were exposed to water. Mean decrease in heart rate (14%) and increases in systolic (9%) and diastolic (5%) blood pressures were seen during immersion. Relative mean finger skin blood flow had an early transient decrease (31%) for 90 s and then returned to baseline values. A strong transient increase was seen in minute ventilation (92%) at 20 s of immersion via tidal volume (85%). There were no consistent differences between the head dorsum, face, and whole head for all variables in response to immersion. The cold-shock response (increased minute ventilation and tidal volume) predominated over the dive response in the initial moments of immersion only. The order of emergence of these responses provides further recommendation to avoid head submersion upon cold water entry. It is important to protect the face, with a facemask, and the head dorsum, with an insulative hood, in cold water.

Obesity: challenges to ventilatory control during exercise--a brief review.

PubMed

Babb, Tony G

2013-11-01

Obesity is a national health issue in the US. Among the many physiological changes induced by obesity, it also presents a unique challenge to ventilatory control during exercise due to increased metabolic demand of moving larger limbs, increased work of breathing due to extra weight on the chest wall, and changes in breathing mechanics. These challenges to ventilatory control in obesity can be inconspicuous or overt among obese adults but for the most part adaptation of ventilatory control during exercise in obesity appears remarkably unnoticed in the majority of obese people. In this brief review, the changes to ventilatory control required for maintaining normal ventilation during exercise will be examined, especially the interaction between respiratory neural drive and ventilation. Also, gaps in our current knowledge will be discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

With age a lower individual breathing reserve is associated with a higher maximal heart rate.

PubMed

Burtscher, Martin; Gatterer, Hannes; Faulhaber, Martin; Burtscher, Johannes

2018-01-01

Maximal heart rate (HRmax) is linearly declining with increasing age. Regular exercise training is supposed to partly prevent this decline, whereas sex and habitual physical activity do not. High exercise capacity is associated with a high cardiac output (HR x stroke volume) and high ventilatory requirements. Due to the close cardiorespiratory coupling, we hypothesized that the individual ventilatory response to maximal exercise might be associated with the age-related HRmax. Retrospective analyses have been conducted on the results of 129 consecutively performed routine cardiopulmonary exercise tests. The study sample comprised healthy subjects of both sexes of a broad range of age (20-86 years). Maximal values of power output, minute ventilation, oxygen uptake and heart rate were assessed by the use of incremental cycle spiroergometry. Linear multivariate regression analysis revealed that in addition to age the individual breathing reserve at maximal exercise was independently predictive for HRmax. A lower breathing reserve due to a high ventilatory demand and/or a low ventilatory capacity, which is more pronounced at a higher age, was associated with higher HRmax. Age explained the observed variance in HRmax by 72% and was improved to 83% when the variable "breathing reserve" was entered. The presented findings indicate an independent association between the breathing reserve at maximal exercise and maximal heart rate, i.e. a low individual breathing reserve is associated with a higher age-related HRmax. A deeper understanding of this association has to be investigated in a more physiological scenario. Copyright © 2017 Elsevier B.V. All rights reserved.

Ventilatory and cardiometabolic responses to unilateral sanding in elderly women with ischemic heart disease: a pilot study.

PubMed

Muraki, T; Kujime, K; Kaneko, T; Su, M; Ueba, Y

1991-08-01

This study was undertaken to investigate how 8 elderly women with ischemic heart disease would respond to a unilateral sanding activity. Three ventilatory measures-expiratory tidal volume, respiratory rate, and expiratory volume--and four cardiometabolic measures--metabolic equivalent, systolic blood pressure, heart rate, and pressure rate product--were continuously recorded during the sanding activity. The two independent variables were angle of the sanding board and sanding velocity. The activity was graded to yield five conditions: (a) sitting at rest; (b) 0 degrees at 15 cycles per min (cpm); (c) 0 degrees at 30 cpm; (d) 15 degrees at 15 cpm; and (e) 15 degrees at 30 cpm. The findings indicated that increasing the angle of the board while holding the velocity constant did not always increase the mean values of the ventilatory and cardiometabolic measures. However, increasing the velocity while holding the angle constant always increased the mean values of the dependent variables. The data also indicated that the metabolic equivalent reached during the sanding activity was no greater than 2, which corresponds to a light activity, such as playing a musical instrument. Replication of the study with a larger sample size may further elucidate the behavior of these two functions during a graded sanding activity. In the present study, a unilateral sanding activity by elderly patients with cardiac impairment was shown to provide valuable data on ventilatory and cardiometabolic functions. The study also demonstrated that a unilateral sanding activity can be safely used as a graded activity in occupational therapy for the cardiac rehabilitation of elderly women.

Acrolein inhalation alters myocardial synchrony and performance at and below exposure concentrations that cause ventilatory responses

EPA Science Inventory

Acrolein is an irritating aldehyde generated during combustion of organic compounds. Altered autonomic activity has been documented following acrolein inhalation, possibly impacting myocardial synchrony and function. Given the ubiquitous nature of acrolein in the environment, we ...

Hemodynamic, ventilatory, and biochemical responses of panic patients and normal controls with sodium lactate infusion and spontaneous panic attacks.

PubMed

Gaffney, F A; Fenton, B J; Lane, L D; Lake, C R

1988-01-01

Hemodynamic, ventilatory, and biochemical variables were measured in ten healthy adults and ten panic patients during infusion of 0.5 mol/L of sodium lactate. Physical activity, fitness level, and ambulatory electrocardiograms were also recorded. Lactate infusion doubled cardiac output, increased blood lactate levels by sixfold, and produced hypernatremia, hypocalcemia, and decreased serum bicarbonate levels in both groups but raised arterial pressure only in the patients. The patients hyperventilated before and during the infusion. Physiological responses and somatic complaints with the infusion differed little between the groups, but emotional complaints were six times more frequent among the panic patients. Eight patients but no control subjects interpreted their symptoms as a panic attack. Heart rate increased with only 14 of 31 recorded spontaneous outpatient panic attacks. Sodium lactate infusions appear to produce panic by mimicking the physiology of spontaneous panic. Treatment with cardioactive agents is not indicated in the absence of cardiopulmonary or autonomic nervous system abnormalities.

Sleep and respiration in microgravity

NASA Technical Reports Server (NTRS)

Prisk, G. K.

1998-01-01

Sleep studies conducted during the STS-90 Neurolab mission are explored. The relationship between sleep, melatonin, and circadian phase is reviewed. The study contained both sleep and awake components. The objectives of the sleep component were to test five hypotheses: that circadian rhythms of core body temperature and urinary melatonin are synchronized to required sleep-wake schedules, that spaceflight results in substantial disruption of sleep, that the pattern of chest and abdominal wall motion alters during the different sleep stages in microgravity, that arterial oxygen saturation is reduced during some stages of sleep in microgravity, and that pre-sleep administration of melatonin during microgravity results in improved sleep quality. The awake component tested three hypotheses: that ventilatory response to carbon dioxide is increased during exposure to microgravity and that this exacerbates sleep disruption, that ventilatory response to hypoxia is increased by exposure to microgravity, and that the improved sleep resulting from the pre-sleep administration of melatonin enhances next day cognition when compared to placebo.

Effects of hypoxia on sympathetic neural control in humans

NASA Technical Reports Server (NTRS)

Smith, M. L.; Muenter, N. K.

2000-01-01

This special issue is principally focused on the time domain of the adaptive mechanisms of ventilatory responses to short-term, long-term and intermittent hypoxia. The purpose of this review is to summarize the limited literature on the sympathetic neural responses to sustained or intermittent hypoxia in humans and attempt to discern the time domain of these responses and potential adaptive processes that are evoked during short and long-term exposures to hypoxia.

Cerebrovascular regulation in men and women: stimulus-specific role of cyclooxygenase

PubMed Central

Peltonen, Garrett L; Harrell, John W; Rousseau, Cameron L; Ernst, Brady S; Marino, Mariah L; Crain, Meghan K; Schrage, William G

2015-01-01

Greater cerebral artery vasodilation mediated by cyclooxygenase (COX) in female animals is unexplored in humans. We hypothesized that young, healthy women would exhibit greater basal cerebral blood flow (CBF) and greater vasodilation during hypoxia or hypercapnia compared to men, mediated by a larger contribution of COX. We measured middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) in 42 adults (24 women, 18 men; 24 ± 1 years) during two visits, in a double-blind, placebo-controlled design (COX inhibition, 100 mg oral indomethacin, Indo). Women were studied early in the follicular phase of the menstrual cycle (days 1–5). Two levels of isocapnic hypoxia (SPO2 = 90% and 80%) were induced for 5-min each. Separately, hypercapnia was induced by increasing end-tidal carbon dioxide (PETCO2) 10 mmHg above baseline. A positive change in MCAv (ΔMCAv) reflected vasodilation. Basal MCAv was greater in women compared to men (P < 0.01) across all conditions. Indo decreased baseline MCAv (P < 0.01) similarly between sexes. Hypoxia increased MCAv (P < 0.01), but ΔMCAv was not different between sexes. Indo did not alter hypoxic vasodilation in either sex. Hypercapnia increased MCAv (P < 0.01), but ΔMCAv was not different between sexes. Indo elicited a large decrease in hypercapnic vasodilation (P < 0.01) that was similar between sexes. During the early follicular phase, women exhibit greater basal CBF than men, but similar vasodilatory responses to hypoxia and hypercapnia. Moreover, COX is not obligatory for hypoxic vasodilation, but plays a vital and similar role in the regulation of basal CBF (∼30%) and hypercapnic response (∼55%) between sexes. PMID:26149282

Ultrasonography evaluation during the weaning process: the heart, the diaphragm, the pleura and the lung.

PubMed

Mayo, P; Volpicelli, G; Lerolle, N; Schreiber, A; Doelken, P; Vieillard-Baron, A

2016-07-01

On a regular basis, the intensivist encounters the patient who is difficult to wean from mechanical ventilatory support. The causes for failure to wean from mechanical ventilatory support are often multifactorial and involve a complex interplay between cardiac and pulmonary dysfunction. A potential application of point of care ultrasonography relates to its utility in the process of weaning the patient from mechanical ventilatory support. This article reviews some applications of ultrasonography that may be relevant to the process of weaning from mechanical ventilatory support. The authors have divided these applications of ultrasonography into four separate categories: the assessment of cardiac, diaphragmatic, and lung function; and the identification of pleural effusion; which can all be evaluated with ultrasonography during a dynamic process in which the intensivist is uniquely positioned to use ultrasonography at the point of care. Ultrasonography may have useful application during the weaning process from mechanical ventilatory support.

High fat diet blunts the effects of leptin on ventilation and on carotid body activity.

PubMed

Ribeiro, Maria J; Sacramento, Joana F; Gallego-Martin, Teresa; Olea, Elena; Melo, Bernardete F; Guarino, Maria P; Yubero, Sara; Obeso, Ana; Conde, Silvia V

2017-12-22

Leptin plays a role in the control of breathing, acting mainly on central nervous system; however, leptin receptors have been recently shown to be expressed in the carotid body (CB), and this finding suggests a physiological role for leptin in the regulation of CB function. Leptin increases minute ventilation in both basal and hypoxic conditions in rats. It increases the frequency of carotid sinus nerve discharge in basal conditions, as well as the release of adenosine from the CB. However, in a metabolic syndrome animal model, the effects of leptin in ventilatory control, carotid sinus nerve activity and adenosine release by the CB are blunted. Although leptin may be involved in triggering CB overactivation in initial stages of obesity and dysmetabolism, resistance to leptin signalling and blunting of responses develops in metabolic syndrome animal models. Leptin plays a role in the control of breathing, acting mainly on central nervous system structures. Leptin receptors are expressed in the carotid body (CB) and this finding has been associated with a putative physiological role of leptin in the regulation of CB function. Since, the CBs are implicated in energy metabolism, here we tested the effects of different concentrations of leptin administration on ventilatory parameters and on carotid sinus nerve (CSN) activity in control and high-fat (HF) diet fed rats, in order to clarify the role of leptin in ventilation control in metabolic disease states. We also investigated the expression of leptin receptors and the neurotransmitters involved in leptin signalling in the CBs. We found that in non-disease conditions, leptin increases minute ventilation in both basal and hypoxic conditions. However, in the HF model, the effect of leptin in ventilatory control is blunted. We also observed that HF rats display an increased frequency of CSN discharge in basal conditions that is not altered by leptin, in contrast to what is observed in control animals. Leptin did not modify intracellular Ca 2+ in CB chemoreceptor cells, but it produced an increase in the release of adenosine from the whole CB. We conclude that CBs represent an important target for leptin signalling, not only to coordinate peripheral ventilatory chemoreflexive drive, but probably also to modulate metabolic variables. We also concluded that leptin signalling is mediated by adenosine release and that HF diets blunt leptin responses in the CB, compromising ventilatory adaptation. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Respiratory Failure

MedlinePlus

... of oxygen in the blood, it's called hypoxemic (HI-pok-SE-mik) respiratory failure. When respiratory failure ... carbon dioxide in the blood, it's called hypercapnic (HI-per-KAP-nik) respiratory failure. Causes Diseases and ...

Dexamethasone mimics aspects of physiological acclimatization to 8 hours of hypoxia but suppresses plasma erythropoietin

PubMed Central

Liu, Chun; Croft, Quentin P. P.; Kalidhar, Swati; Brooks, Jerome T.; Herigstad, Mari; Smith, Thomas G.; Dorrington, Keith L.

2013-01-01

Dexamethasone ameliorates the severity of acute mountain sickness (AMS) but it is unknown whether it obtunds normal physiological responses to hypoxia. We studied whether dexamethasone enhanced or inhibited the ventilatory, cardiovascular, and pulmonary vascular responses to sustained (8 h) hypoxia. Eight healthy volunteers were studied, each on four separate occasions, permitting four different protocols. These were: dexamethasone (20 mg orally) beginning 2 h before a control period of 8 h of air breathing; dexamethasone with 8 h of isocapnic hypoxia (end-tidal Po2 = 50 Torr); placebo with 8 h of air breathing; and placebo with 8 h of isocapnic hypoxia. Before and after each protocol, the following were determined under both euoxic and hypoxic conditions: ventilation; pulmonary artery pressure (estimated using echocardiography to assess maximum tricuspid pressure difference); heart rate; and cardiac output. Plasma concentrations of erythropoietin (EPO) were also determined. Dexamethasone had no early (2-h) effect on any variable. Both dexamethasone and 8 h of hypoxia increased euoxic values of ventilation, pulmonary artery pressure, and heart rate, together with the ventilatory sensitivity to acute hypoxia. These effects were independent and additive. Eight hours of hypoxia, but not dexamethasone, increased the sensitivity of pulmonary artery pressure to acute hypoxia. Dexamethasone, but not 8 h of hypoxia, increased both cardiac output and systemic arterial pressure. Dexamethasone abolished the rise in EPO induced by 8 h of hypoxia. In summary, dexamethasone enhances ventilatory acclimatization to hypoxia. Thus, dexamethasone in AMS may improve oxygenation and thereby indirectly lower pulmonary artery pressure. PMID:23393065

The effect of music therapy on physiological signs of anxiety in patients receiving mechanical ventilatory support.

PubMed

Korhan, Esra Akin; Khorshid, Leyla; Uyar, Mehmet

2011-04-01

The aim of this study was to investigate if relaxing music is an effective method of reducing the physiological signs of anxiety in patients receiving mechanical ventilatory support. Few studies have focused on the effect of music on physiological signs of anxiety in patients receiving mechanical ventilatory support. A study-case-control, experimental repeated measures design was used. Sixty patients aged 18-70 years, receiving mechanical ventilatory support and hospitalised in the intensive care unit, were taken as a convenience sample. Participants were randomised to a control group or intervention group, who received 60 minutes of music therapy. Classical music was played to patients using media player (MP3) and headphones. Subjects had physiological signs taken immediately before the intervention and at the 30th, 60th and 90th minutes of the intervention. Physiological signs of anxiety assessed in this study were mean systolic and diastolic blood pressure, pulse rate, respiratory rate and oxygen saturation in blood measured by pulse oxymetry. Data were collected over eight months in 2006-2007. The music group had significantly lower respiratory rates, and systolic and diastolic blood pressure, than the control group. This decrease improved progressively in the 30th, 60th and 90th minutes of the intervention, indicating a cumulative dose effect. Music can provide an effective method of reducing potentially harmful physiological responses arising from anxiety. As indicated by the results of this study, music therapy can be supplied to allay anxiety in patients receiving mechanical ventilation. Nurses may include music therapy in the routine care of patients receiving mechanical ventilation. © 2011 Blackwell Publishing Ltd.

Respiratory Mechanical and Cardiorespiratory Consequences of Cycling with Aerobars.

PubMed

Charlton, Jesse M; Ramsook, Andrew H; Mitchell, Reid A; Hunt, Michael A; Puyat, Joseph H; Guenette, Jordan A

2017-12-01

Aerobars place a cyclist in a position where the trunk is flexed forward and the elbows are close to the midline of the body. This position is known to improve cycling aerodynamics and time trial race performance compared with upright cycling positions. However, the aggressive nature of this position may have important cardiorespiratory and metabolic consequences. The purpose of this investigation was to examine the respiratory mechanical, ventilatory, metabolic, and sensory consequences of cycling while using aerobars during laboratory-based cycling. Eleven endurance-trained male cyclists (age, 26 ± 9 yr; V˙O2peak, 55 ± 5 mL·kg·min) were recruited. Visit 1 consisted of an incremental cycling test to determine peak power output. Visit 2 consisted of 6-min bouts of constant load cycling at 70% of peak incremental power output in the aerobar position, drop position, and upright position while grasping the brake hoods. Metabolic and ventilatory responses were measured using a commercially available metabolic cart, and respiratory pressures were measured using an esophageal catheter. Cycling in the aerobar position significantly increased the work of breathing (Wb), power of breathing (Pb), minute ventilation, ventilatory equivalent for oxygen and carbon dioxide, and transdiaphragmatic pressure compared with the upright position. Increases in the Wb and Pb in the aerobars relative to the upright position were strongly correlated with the degree of thoracic restriction, measured as the shoulder-to-aerobar width ratio (Wb: r = 0.80, P = 0.01; Pb: r = 0.69, P = 0.04). Aerobars significantly increase the mechanical cost of breathing and leads to greater ventilatory inefficiency compared with upright cycling. Future work is needed to optimize aerobar width to minimize the respiratory mechanical consequences while optimizing aerodynamics.

A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting--a prospective, multicenter validation study.

PubMed

Villar, Jesús; Pérez-Méndez, Lina; Blanco, Jesús; Añón, José Manuel; Blanch, Lluís; Belda, Javier; Santos-Bouza, Antonio; Fernández, Rosa Lidia; Kacmarek, Robert M

2013-04-01

The PaO2/FiO2 is an integral part of the assessment of patients with acute respiratory distress syndrome (ARDS). The American-European Consensus Conference definition does not mandate any standardization procedure. We hypothesized that the use of PaO2/FiO2 calculated under a standard ventilatory setting within 24 h of ARDS diagnosis allows a more clinically relevant ARDS classification. We studied 452 ARDS patients enrolled prospectively in two independent, multicenter cohorts treated with protective mechanical ventilation. At the time of ARDS diagnosis, patients had a PaO2/FiO2 ≤ 200. In the derivation cohort (n = 170), we measured PaO2/FiO2 with two levels of positive end-expiratory pressure (PEEP) (≥ 5 and ≥ 10 cmH2O) and two levels of FiO2 (≥ 0.5 and 1.0) at ARDS onset and 24 h later. Dependent upon PaO2 response, patients were reclassified into three groups: mild (PaO2/FiO2 > 200), moderate (PaO2/FiO2 101-200), and severe (PaO2/FiO2 ≤ 100) ARDS. The primary outcome measure was ICU mortality. The standard ventilatory setting that reached the highest significance difference in mortality among these categories was tested in a separate cohort (n = 282). The only standard ventilatory setting that identified the three PaO2/FiO2 risk categories in the derivation cohort was PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 at 24 h after ARDS onset (p = 0.0001). Using this ventilatory setting, patients in the validation cohort were reclassified as having mild ARDS (n = 47, mortality 17 %), moderate ARDS (n = 149, mortality 40.9 %), and severe ARDS (n = 86, mortality 58.1 %) (p = 0.00001). Our method for assessing PaO2/FiO2 greatly improved risk stratification of ARDS and could be used for enrolling appropriate ARDS patients into therapeutic clinical trials.

High pressure versus high intensity noninvasive ventilation in stable hypercapnic chronic obstructive pulmonary disease: a randomized crossover trial.

PubMed

Murphy, Patrick B; Brignall, Kate; Moxham, John; Polkey, Michael I; Davidson, A Craig; Hart, Nicholas

2012-01-01

High-intensity (high-pressure and high backup rate) noninvasive ventilation has recently been advocated for the management of stable hypercapnic chronic obstructive pulmonary disease (COPD). However, the relative contributions of high inspiratory pressure and high backup rate to ventilator adherence and physiological outcome have not been investigated. Patients with stable hypercapnic COPD (daytime PaCO(2) > 6 kPa) and nocturnal hypoventilation were enrolled. Patients were randomly allocated to high-pressure and high backup rate (high-intensity) and high-pressure and low backup rate (high-pressure) for a 6-week period. At the end of the first treatment period, patients were switched to the alternative treatment. The primary outcome measure was mean nightly ventilator usage. Twelve patients were recruited, with seven completing the 12-week trial protocol. The mean patient age was 71 ± 8 years, with a forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) of 50% ± 13% and FEV(1) of 32% ± 12%. The baseline PaCO(2) and PaO(2) were 8.6 ± 1.7 kPa and 7.3 ± 1.4 kPa, respectively. There was no significant difference demonstrated in mean nightly ventilator usage between the high-intensity and high-pressure groups (difference of 4 minutes; 95% confidence interval -45 to 53; P = 0.9). Furthermore, there were no differences in any of the secondary endpoints, with the exception of the respiratory domain of the Severe Respiratory Insufficiency questionnaire, which was lower in the high-intensity arm than in the high-pressure arm (57 ± 11 versus 69 ± 16; P < 0.05). There was no additional benefit, in terms of night-time ventilator adherence or any of the other measured parameters, demonstrated by addition of a high backup rate to high-pressure noninvasive ventilation. These data suggest that it is the high-pressure component of the high-intensity noninvasive ventilation approach that plays the important therapeutic role in the management of hypercapnic respiratory failure in COPD patients.

The influence of chronic hypoxia upon chemoreception

PubMed Central

Powell, Frank L.

2007-01-01

Carotid body chemoreceptors are essential for time-dependent changes in ventilatory control during chronic hypoxia. Early theories of ventilatory acclimatization to hypoxia focused on time-dependent changes in known ventilatory stimuli, such as small changes in arterial pH that may play a significant role in some species. However, plasticity in the cellular and molecular mechanisms of carotid body chemoreception play a major role in ventilatory acclimatization to hypoxia in all species studied. Chronic hypoxia causes changes in (a) ion channels (potassium, sodium, calcium) to increase glomus cell excitability, and (b) neurotransmitters (dopamine, acetylcholine, ATP) and neuromodulators (endothelin-1) to increase carotid body afferent activity for a given PO2 and optimize O2-sensitivity. O2-sensing heme-containing molecules in the carotid body have not been studied in chronic hypoxia. Plasticity in medullary respiratory centers processing carotid body afferent input also contributes to ventilatory acclimatization to hypoxia. It is not known if the same mechanisms occur in patients with chronic hypoxemia from lung disease or high altitude natives. PMID:17291837

Effects of movement and work load in patients with congenital central hypoventilation syndrome.

PubMed

Hager, Alfred; Koch, Walter; Stenzel, Heike; Hess, John; Schöber, Johannes

2007-04-01

Patients with congenital central hypoventilation syndrome lack ventilatory chemosensitivity and depend at least in part on the ergoreceptor function during exercise. In these patients a substantial increase of ventilation has been reported for passive movement during sleep as well as active movement on a treadmill. The aim of the study was to investigate ventilatory response to an increasing work load with constant movement. Eighteen patients and 17 healthy volunteers performed a cardiopulmonary exercise test on a bicycle pedaling at a constant rate of about 60 revolutions per minute throughout the entire test. The patients were able to exercise adequately and showed normal peak oxygen uptake. There was a steep rise in minute ventilation in both groups at the start of exercise, yet there was only a minor increase in both groups during the increase of workload up to the anaerobic threshold. After the anaerobic threshold, there was again an increase in ventilation in both groups, but the increase was less prominent in the patient group. Ventilation in patients with congenital central hypoventilation syndrome is increased during exercise caused both by movement (mechanoreceptors) and by anaerobic workload. This facilitates a normal ventilatory drive up to the anaerobic threshold and a normal exercise capacity in these patients.

Ventilatory Responses at Peak Exercise in Endurance-Trained Obese Adults

PubMed Central

Lorenzo, Santiago

2013-01-01

Background: Alterations in respiratory mechanics predispose healthy obese individuals to low lung volume breathing, which places them at risk of developing expiratory flow limitation (EFL). The high ventilatory demand in endurance-trained obese adults further increases their risk of developing EFL and increases their work of breathing. The objective of this study was to investigate the prevalence and magnitude of EFL in fit obese (FO) adults via measurements of breathing mechanics and ventilatory dynamics during exercise. Methods: Ten (seven women and three men) FO (mean ± SD, 38 ± 5 years, 38% ± 5% body fat) and 10 (seven women and three men) control obese (CO) (38 ± 5 years, 39% ± 5% body fat) subjects underwent hydrostatic weighing, pulmonary function testing, cycle exercise testing, and the determination of the oxygen cost of breathing during eucapnic voluntary hyperpnea. Results: There were no differences in functional residual capacity (43% ± 6% vs 40% ± 9% total lung capacity [TLC]), residual volume (21% ± 4% vs 21% ± 4% TLC), or FVC (111% ± 13% vs 104% ± 15% predicted) between FO and CO subjects, respectively. FO subjects had higher FEV1 (111% ± 13% vs 99% ± 11% predicted), TLC (106% ± 14% vs 94% ± 7% predicted), peak expiratory flow (123% ± 14% vs 106% ± 13% predicted), and maximal voluntary ventilation (128% ± 15% vs 106% ± 13% predicted) than did CO subjects. Peak oxygen uptake (129% ± 16% vs 86% ± 15% predicted), minute ventilation (128 ± 35 L/min vs 92 ± 25 L/min), and work rate (229 ± 54 W vs 166 ± 55 W) were higher in FO subjects. Mean inspiratory (4.65 ± 1.09 L/s vs 3.06 ± 1.21 L/s) and expiratory (4.15 ± 0.95 L/s vs 2.98 ± 0.76L/s) flows were greater in FO subjects, which yielded a greater breathing frequency (51 ± 8 breaths/min vs 41 ± 10 breaths/min) at peak exercise in FO subjects. Mechanical ventilatory constraints in FO subjects were similar to those in CO subjects despite the greater ventilatory demand in FO subjects. Conclusion: FO individuals achieve high ventilations by increasing breathing frequency, matching the elevated metabolic demand associated with high fitness. They do this without developing meaningful ventilatory constraints. Therefore, endurance-trained obese individuals with higher lung function are not limited by breathing mechanics during peak exercise, which may allow healthy obese adults to participate in vigorous exercise training. PMID:23722607

Ventilatory responses at peak exercise in endurance-trained obese adults.

PubMed

Lorenzo, Santiago; Babb, Tony G

2013-10-01

Alterations in respiratory mechanics predispose healthy obese individuals to low lung volume breathing, which places them at risk of developing expiratory flow limitation (EFL). The high ventilatory demand in endurance-trained obese adults further increases their risk of developing EFL and increases their work of breathing. The objective of this study was to investigate the prevalence and magnitude of EFL in fit obese (FO) adults via measurements of breathing mechanics and ventilatory dynamics during exercise. Ten (seven women and three men) FO (mean ± SD, 38 ± 5 years, 38% ± 5% body fat) and 10 (seven women and three men) control obese (CO) (38 ± 5 years, 39% ± 5% body fat) subjects underwent hydrostatic weighing, pulmonary function testing, cycle exercise testing, and the determination of the oxygen cost of breathing during eucapnic voluntary hyperpnea. There were no differences in functional residual capacity (43% ± 6% vs 40% ± 9% total lung capacity [TLC]), residual volume (21% ± 4% vs 21% ± 4% TLC), or FVC (111% ± 13% vs 104% ± 15% predicted) between FO and CO subjects, respectively. FO subjects had higher FEV1 (111% ± 13% vs 99% ± 11% predicted), TLC (106% ± 14% vs 94% ± 7% predicted), peak expiratory flow (123% ± 14% vs 106% ± 13% predicted), and maximal voluntary ventilation (128% ± 15% vs 106% ± 13% predicted) than did CO subjects. Peak oxygen uptake (129% ± 16% vs 86% ± 15% predicted), minute ventilation (128 ± 35 L/min vs 92 ± 25 L/min), and work rate (229 ± 54 W vs 166 ± 55 W) were higher in FO subjects. Mean inspiratory (4.65 ± 1.09 L/s vs 3.06 ± 1.21 L/s) and expiratory (4.15 ± 0.95 L/s vs 2.98 ± 0.76 L/s) flows were greater in FO subjects, which yielded a greater breathing frequency (51 ± 8 breaths/min vs 41 ± 10 breaths/min) at peak exercise in FO subjects. Mechanical ventilatory constraints in FO subjects were similar to those in CO subjects despite the greater ventilatory demand in FO subjects. FO individuals achieve high ventilations by increasing breathing frequency, matching the elevated metabolic demand associated with high fitness. They do this without developing meaningful ventilatory constraints. Therefore, endurance-trained obese individuals with higher lung function are not limited by breathing mechanics during peak exercise, which may allow healthy obese adults to participate in vigorous exercise training.

Comparing cerebrovascular reactivity measured using BOLD and cerebral blood flow MRI: The effect of basal vascular tension on vasodilatory and vasoconstrictive reactivity

PubMed Central

Halani, Sheliza; Kwinta, Jonathan B.; Golestani, Ali M.; Khatamian, Yasha B.; Chen, J. Jean

2016-01-01

Cerebrovascular reactivity (CVR) is an important metric of cerebrovascular health. While the BOLD fMRI method in conjunction with carbon-dioxide (CO2) based vascular manipulation has been the most commonly used, the BOLD signal is not a direct measure of vascular changes, and the use of arterial-spin labeling (ASL) cerebral blood flow (CBF) imaging is increasingly advocated. Nonetheless, given the differing dependencies of BOLD and CBF on vascular baseline conditions and the diverse CO2 manipulation types currently used in the literature, knowledge of potential biases introduced by each technique is critical for the interpretation of CVR measurements. In this work, we use simultaneous BOLD-CBF acquisitions during both vasodilatory (hypercapnic) and vasoconstrictive (hypocapnic) stimuli to measure CVR. We further imposed different levels of baseline vascular tension by inducing hypercapnic and hypocapnic baselines, separately from normocapnia by 4 mm Hg. We saw significant and diverse dependencies on vascular stimulus and baseline condition in both BOLD and CBF CVR measurements: (i) BOLD-based CVR is more sensitive to basal vascular tension than CBF-based CVR; (ii) the use of a combination of vasodilatory and vasoconstrictive stimuli maximizes the sensitivity of CBF-based CVR to vascular tension changes; (iii) the BOLD and CBF vascular response delays are both significantly lengthened at predilated baseline. As vascular tension can often be altered by potential pathology, our findings are important considerations when interpreting CVR measurements in health and disease. PMID:25655446

A historical perspective on ventilator management.

PubMed

Shapiro, B A

1994-02-01

Paralysis via neuromuscular blockade in ICU patients requires mechanical ventilation. This review historically addresses the technological advances and scientific information upon which ventilatory management concepts are based, with special emphasis on the influence such concepts have had on the use of neuromuscular blocking agents. Specific reference is made to the scientific information and technological advances leading to the newer concepts of ventilatory management. Information from > 100 major studies in the peer-reviewed medical literature, along with the author's 25 yrs of clinical experience and academic involvement in acute respiratory care is presented. Nomenclature related to ventilatory management is specifically defined and consistently utilized to present and interpret the data. Pre-1970 ventilatory management is traced from the clinically unacceptable pressure-limited devices to the reliable performance of volume-limited ventilators. The scientific data and rationale that led to the concept of relatively large tidal volume delivery are reviewed in the light of today's concerns regarding alveolar overdistention, control-mode dyssynchrony, and auto-positive end-expiratory pressure. Also presented are the post-1970 scientific rationales for continuous positive airway pressure/positive end-expiratory pressure therapy, avoidance of alveolar hyperxia, and partial ventilatory support techniques (intermittent mandatory ventilation/synchronized intermittent mandatory ventilation). The development of pressure-support devices is discussed and the capability of pressure-control techniques is presented. The rationale for more recent concepts of total ventilatory support to avoid ventilator-induced lung injury is presented. The traditional techniques utilizing volume-preset ventilators with relatively large tidal volumes remain valid and desirable for the vast majority of patients requiring mechanical ventilation. Neuromuscular blockade is best avoided in these patients. However, adequate analgesia, amnesia, and sedation are required. For patients with severe lung disease, alveolar overdistention and hyperoxia should be avoided and may be best accomplished by total ventilatory support techniques, such as pressure control. Total ventilatory support requires neuromuscular blockade and may not provide eucapnic ventilation.

Bicarbonate sensing in mouse cortical astrocytes during extracellular acid/base disturbances.

PubMed

Theparambil, Shefeeq M; Naoshin, Zinnia; Defren, Sabrina; Schmaelzle, Jana; Weber, Tobias; Schneider, Hans-Peter; Deitmer, Joachim W

2017-04-15

The present study suggests that the electrogenic sodium-bicarbonate cotransporter, NBCe1, supported by carbonic anhydrase II, CAII, provides an efficient mechanism of bicarbonate sensing in cortical astrocytes. This mechanism is proposed to play a major role in setting the pH i responses to extracellular acid/base challenges in astrocytes. A decrease in extracellular [HCO 3 - ] during isocapnic acidosis and isohydric hypocapnia, or an increase in intracellular [HCO 3 - ] during hypercapnic acidosis, was effectively sensed by NBCe1, which carried bicarbonate out of the cells under these conditions, and caused an acidification and sodium fall in WT astrocytes, but not in NBCe1-knockout astrocytes. Isocapnic acidosis, hypercapnic acidosis and isohydric hypocapnia evoked inward currents in NBCe1- and CAII-expressing Xenopus laevis oocytes, but not in native oocytes, suggesting that NBCe1 operates in the outwardly directed mode under these conditions consistent with our findings in astrocytes. We propose that bicarbonate sensing of astrocytes may have functional significance during extracellular acid/base disturbances in the brain, as it not only alters intracellular pH/[HCO 3 - ]-dependent functions of astrocytes, but also modulates the extracellular pH/[HCO 3 - ] in brain tissue. Extracellular acid/base status of the mammalian brain undergoes dynamic changes during many physiological and pathological events. Although intracellular pH (pH i ) of astrocytes responds to extracellular acid/base changes, the mechanisms mediating these changes have remained unresolved. We have previously shown that the electrogenic sodium-bicarbonate cotransporter, NBCe1, is a high-affinity bicarbonate carrier in cortical astrocytes. In the present study, we investigated whether NBCe1 plays a role in bicarbonate sensing in astrocytes, and in determining the pH i responses to extracellular acid/base challenges. We measured changes in intracellular H + and Na + in astrocytes from wild-type (WT) and from NBCe1-knockout (KO) mice, using ion-selective dyes, during isocapnic acidosis, hypercapnic acidosis and hypocapnia. We also analysed NBCe1-mediated membrane currents in Xenopus laevis oocytes under similar conditions. Comparing WT and NBCe1-KO astrocytes, we could dissect the contribution of NBCe1, of diffusion of CO 2 across the cell membrane and, after blocking carbonic anhydrase (CA) activity with ethoxyzolamide, of the role of CA, for the amplitude and rate of acid/base fluxes. Our results suggest that NBCe1 transport activity in astrocytes, supported by CA activity, renders astrocytes bicarbonate sensors in the mouse cortex. NBCe1 carried bicarbonate into and out of the cell by sensing the variations of transmembrane [HCO 3 - ], irrespective of the changes in intra- and extracellular pH, and played a major role in setting pH i responses to the extracellular acid/base challenges. We propose that bicarbonate sensing of astrocytes may have potential functional significance during extracellular acid/base alterations in the brain. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Bicarbonate sensing in mouse cortical astrocytes during extracellular acid/base disturbances

PubMed Central

Naoshin, Zinnia; Defren, Sabrina; Schmaelzle, Jana; Weber, Tobias; Schneider, Hans‐Peter

2017-01-01

Key points The present study suggests that the electrogenic sodium–bicarbonate cotransporter, NBCe1, supported by carbonic anhydrase II, CAII, provides an efficient mechanism of bicarbonate sensing in cortical astrocytes. This mechanism is proposed to play a major role in setting the pHi responses to extracellular acid/base challenges in astrocytes.A decrease in extracellular [HCO3 −] during isocapnic acidosis and isohydric hypocapnia, or an increase in intracellular [HCO3 −] during hypercapnic acidosis, was effectively sensed by NBCe1, which carried bicarbonate out of the cells under these conditions, and caused an acidification and sodium fall in WT astrocytes, but not in NBCe1‐knockout astrocytes.Isocapnic acidosis, hypercapnic acidosis and isohydric hypocapnia evoked inward currents in NBCe1‐ and CAII‐expressing Xenopus laevis oocytes, but not in native oocytes, suggesting that NBCe1 operates in the outwardly directed mode under these conditions consistent with our findings in astrocytes.We propose that bicarbonate sensing of astrocytes may have functional significance during extracellular acid/base disturbances in the brain, as it not only alters intracellular pH/[HCO3 −]‐dependent functions of astrocytes, but also modulates the extracellular pH/[HCO3 −] in brain tissue. Abstract Extracellular acid/base status of the mammalian brain undergoes dynamic changes during many physiological and pathological events. Although intracellular pH (pHi) of astrocytes responds to extracellular acid/base changes, the mechanisms mediating these changes have remained unresolved. We have previously shown that the electrogenic sodium–bicarbonate cotransporter, NBCe1, is a high‐affinity bicarbonate carrier in cortical astrocytes. In the present study, we investigated whether NBCe1 plays a role in bicarbonate sensing in astrocytes, and in determining the pHi responses to extracellular acid/base challenges. We measured changes in intracellular H+ and Na+ in astrocytes from wild‐type (WT) and from NBCe1‐knockout (KO) mice, using ion‐selective dyes, during isocapnic acidosis, hypercapnic acidosis and hypocapnia. We also analysed NBCe1‐mediated membrane currents in Xenopus laevis oocytes under similar conditions. Comparing WT and NBCe1‐KO astrocytes, we could dissect the contribution of NBCe1, of diffusion of CO2 across the cell membrane and, after blocking carbonic anhydrase (CA) activity with ethoxyzolamide, of the role of CA, for the amplitude and rate of acid/base fluxes. Our results suggest that NBCe1 transport activity in astrocytes, supported by CA activity, renders astrocytes bicarbonate sensors in the mouse cortex. NBCe1 carried bicarbonate into and out of the cell by sensing the variations of transmembrane [HCO3 −], irrespective of the changes in intra‐ and extracellular pH, and played a major role in setting pHi responses to the extracellular acid/base challenges. We propose that bicarbonate sensing of astrocytes may have potential functional significance during extracellular acid/base alterations in the brain. PMID:27981578

Respiratory disability in coal miners

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morgan, W.K.C.; Lapp, N.L.; Seaton, D.

1980-06-20

It has been suggested that the assessment of ventilatory capacity alone is inadequate for the determination of disabling occupational respiratory impairment in coal miners. The Department of Labor has accepted this view and now routinely requests blood gas analyses in those claimants not meeting the ventilatory criteria. We tested the validity of this contention by selecting two groups of coal miners claiming total disability. The first consisted of 150 claimants who were referred for spirometry, while the second consisted of 50 claimants who had been referred for blood gas studies. Of those in group 1, eight met the extant criteriamore » for disability, while only two of those in group 2 satisfied the criteria, and, in both, cardiac disease was responsible. We conclude that blood gas analyses are unnecessary in the determination of pulmonary disability in coal miners.« less

Anaesthetic management of sleep-disordered breathing in adults.

PubMed

Hillman, David R; Chung, Frances

2017-02-01

Anaesthesia and sleep are different states of unconsciousness with considerable physiological common ground. Because of their shared depressant effects on muscle activation and ventilatory drive, patients with anatomically compromised airways will tend to obstruct in either state and those with impaired ventilatory capacity will tend to hypoventilate. Breathing behaviour in one state is predictive of that in the other. An essential difference is that while arousal responses are preserved during sleep, they are depressed during sedation and abolished by anaesthesia. This renders patients with sleep-related breathing disorders vulnerable to hypoventilation and asphyxia when deeply sedated. Addressing this vulnerability requires a systematic approach to identification of patients and circumstances that magnify this risk, and methods of managing it that seek to reconcile the need for safety with cost-effective use of resources. © 2016 Asian Pacific Society of Respirology.

Cigarette smoke-induced hypercapnic emphysema in C3H mice is associated with increases of macrophage metalloelastase and substance P in the lungs.

PubMed

Xu, J; Xu, F; Wang, R; Seagrave, Jc; Lin, Y; March, T H

2007-01-01

The authors tested whether macrophage metalloelastase (MMP-12) and substance P (SP) were increased in the cigarette smoke (CS)-exposed female C3H/HeN mice with hypercapnic emphysema. The authors found that as compared to control (filtered air), 16 weeks of CS exposure significantly up-regulated mRNA and protein levels of MMP-12, the ratio of MMP-12/tissue inhibitor of matrix metalloproteinase-1, and SP/preprotachykinin-A (a precursor to SP) in the lungs. Importantly, a significant correlation was found between MMP-12 and SP, and between MMP-12/SP and the degrees of hypoxemia/hypercapnia denoted in CS-exposed mice. These data suggest a possible involvement of SP and MMP-12 in the pathogenesis of severe COPD.

[The role of VEGF, HSP-70 and protein S-100B in the potentiation effect of the neuroprotective effect of hypercapnic hypoxia].

PubMed

Bespalov, A G; Tregub, P P; Kulikov, V P; Pijanzin, A I; Belousov, A A

2014-01-01

Studied the role of VEGF, HSP-70 and S-100B in potentiating hypercapnia neuroprotective effect of hypoxia. Demonstrated that neuroprotective effects when exposed hypercapnic hypoxia-mediated protein synthesis increased S-100B, mainly due to the action of carbon dioxide, and not oxygen deficiency. Neuroprotective effects of HSP-70 due to hypoxia, but the combined effect of hypoxia and hypercapnia gives a significant increase in the synthesis of HSP-70 in comparison with the isolated effect of hypoxia. Vascularization activated equally as hypoxia and hypercapnia, without adding significant effects in combination. This suggests dominant effect hypercapnia, hypoxia compared in neuroprotection mechanisms related to protein S-100B, but not the protein VEGF, hypercapnia and potentiate the neuroprotective efficacy of hypoxia-related protein HSP-70.

Periodicity during hypercapnic and hypoxic stimulus is crucial in distinct aspects of phrenic nerve plasticity.

PubMed

Stipica, I; Pavlinac Dodig, I; Pecotic, R; Dogas, Z; Valic, Z; Valic, M

2016-01-01

This study was undertaken to determine pattern sensitivity of phrenic nerve plasticity in respect to different respiratory challenges. We compared long-term effects of intermittent and continuous hypercapnic and hypoxic stimuli, and combined intermittent hypercapnia and hypoxia on phrenic nerve plasticity. Adult, male, urethane-anesthetized, vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats were exposed to: acute intermittent hypercapnia (AIHc or AIHc(O2)), acute intermittent hypoxia (AIH), combined intermittent hypercapnia and hypoxia (AIHcH), continuous hypercapnia (CHc), or continuous hypoxia (CH). Peak phrenic nerve activity (pPNA) and burst frequency were analyzed during baseline (T0), hypercapnia or hypoxia exposures, at 15, 30, and 60 min (T60) after the end of the stimulus. Exposure to acute intermittent hypercapnia elicited decrease of phrenic nerve frequency from 44.25+/-4.06 at T0 to 35.29+/-5.21 at T60, (P=0.038, AIHc) and from 45.5+/-2.62 to 37.17+/-3.68 breaths/min (P=0.049, AIHc(O2)), i.e. frequency phrenic long term depression was induced. Exposure to AIH elicited increase of pPNA at T60 by 141.0+/-28.2 % compared to baseline (P=0.015), i.e. phrenic long-term facilitation was induced. Exposure to AIHcH, CHc, or CH protocols failed to induce long-term plasticity of the phrenic nerve. Thus, we conclude that intermittency of the hypercapnic or hypoxic stimuli is needed to evoke phrenic nerve plasticity.

Patient-ventilator asynchrony affects pulse pressure variation prediction of fluid responsiveness.

PubMed

Messina, Antonio; Colombo, Davide; Cammarota, Gianmaria; De Lucia, Marta; Cecconi, Maurizio; Antonelli, Massimo; Corte, Francesco Della; Navalesi, Paolo

2015-10-01

During partial ventilatory support, pulse pressure variation (PPV) fails to adequately predict fluid responsiveness. This prospective study aims to investigate whether patient-ventilator asynchrony affects PPV prediction of fluid responsiveness during pressure support ventilation (PSV). This is an observational physiological study evaluating the response to a 500-mL fluid challenge in 54 patients receiving PSV, 27 without (Synch) and 27 with asynchronies (Asynch), as assessed by visual inspection of ventilator waveforms by 2 skilled blinded physicians. The area under the curve was 0.71 (confidence interval, 0.57-0.83) for the overall population, 0.86 (confidence interval, 0.68-0.96) in the Synch group, and 0.53 (confidence interval, 0.33-0.73) in the Asynch group (P = .018). Sensitivity and specificity of PPV were 78% and 89% in the Synch group and 36% and 46% in the Asynch group. Logistic regression showed that the PPV prediction was influenced by patient-ventilator asynchrony (odds ratio, 8.8 [2.0-38.0]; P < .003). Of the 27 patients without asynchronies, 12 had a tidal volume greater than or equal to 8 mL/kg; in this subgroup, the rate of correct classification was 100%. Patient-ventilator asynchrony affects PPV performance during partial ventilatory support influencing its efficacy in predicting fluid responsiveness. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of pyridostigmine on in vivo and in vitro respiratory muscle of mdx mice.

PubMed

Amancio, Gabriela de Cássia Sousa; Grabe-Guimarães, Andrea; Haikel, Dridi; Moreau, Johan; Barcellos, Neila Marcia Silva; Lacampagne, Alain; Matecki, Stefan; Cazorla, Olivier

2017-09-01

The current work was conducted to verify the contribution of neuromuscular transmission defects at the neuromuscular junction to Duchenne Muscular Dystrophy disease progression and respiratory dysfunction. We tested pyridostigmine and pyridostigmine encapsulated in liposomes (liposomal PYR), an acetylcholinesterase inhibitor to improve muscular contraction on respiratory muscle function in mdx mice at different ages. We evaluated in vivo with the whole-body plethysmography, the ventilatory response to hypercapnia, and measured in vitro diaphragm strength in each group. Compared to C57BL10 mice, only 17 and 22 month-old mdx presented blunted ventilatory response, under normocapnia and hypercapnia. Free pyridostigmine (1mg/kg) was toxic to mdx mice, unlike liposomal PYR, which did not show any side effect, confirming that the encapsulation in liposomes is effective in reducing the toxic effects of this drug. Treatment with liposomal PYR, either acute or chronic, did not show any beneficial effect on respiratory function of this DMD experimental model. The encapsulation in liposomes is effective to abolish toxic effects of drugs. Copyright © 2017. Published by Elsevier B.V.

Ventilatory response to carbon dioxide in young athletes: a family study.

PubMed

Saunders, N A; Leeder, S R; Rebuck, A S

1976-04-01

Ventilatory response to carbon dioxide (deltaVE/deltaPCO2) was measured in 23 teenage swimmers chosen by their coach for their potential for future athletic success. Siblings and parents of these swimmers were also studied. We found a strong relation between siblings' de;taVE/DELTAPCO2, whether or not they were swimmers (r=0.71, P less than 0.01). A weaker relationship was found between mother's and children's deltaVE/DELTAPCO2 (r==0.39, P less than 0.01). No association was found between swimming training and deltaVE/deltaPCO2. One swimmer 12 years of age had an extremely low deltaVE/PCO2 (0.42 liter per min per mm Hg) She was the only swimmer among these 23 potential champions to achieve international success in endurance events in the 2 years after the study. We concluded that family factors are important determinants of a subject's deltaVE/PCO2 and suggest that measurement of this aspect of chemical drive to breathing in young athletes may help identify those most likely to succeed in endurance events.

The individual response to training and competition at altitude.

PubMed

Chapman, Robert F

2013-12-01

Performance in athletic activities that include a significant aerobic component at mild or moderate altitudes shows a large individual variation. Physiologically, a large portion of the negative effect of altitude on exercise performance can be traced to limitations of oxygen diffusion, either at the level of the alveoli or the muscle microvasculature. In the lung, the ability to maintain arterial oxyhaemoglobin saturation (SaO₂) appears to be a primary factor, ultimately influencing oxygen delivery to the periphery. SaO₂ in hypoxia can be defended by increasing ventilatory drive; however, during heavy exercise, many athletes demonstrate limitations to expiratory flow and are unable to increase ventilation in hypoxia. Additionally, increasing ventilatory work in hypoxia may actually be negative for performance, if dyspnoea increases or muscle blood flow is reduced secondary to an increased sympathetic outflow (eg, the muscle metaboreflex response). Taken together, some athletes are clearly more negatively affected during exercise in hypoxia than other athletes. With careful screening, it may be possible to develop a protocol for determining which athletes may be the most negatively affected during competition and/or training at altitude.

Why do nonsurvivors from community-acquired pneumonia not receive ventilatory support?

PubMed

Bauer, Torsten T; Welte, Tobias; Strauss, Richard; Bischoff, Helge; Richter, Klaus; Ewig, Santiago

2013-08-01

We investigated rates and predictors of ventilatory support during hospitalization in seemingly not severely compromised nonsurvivors of community-acquired pneumonia (CAP). We used the database from the German nationwide mandatory quality assurance program including all hospitalized patients with CAP from 2007 to 2011. We selected a population not residing in nursing homes, not bedridden, and not referred from another hospital. Predictors of ventilatory support were identified using a multivariate analysis. Overall, 563,901 patients (62.3% of the whole population) were included. Mean age was 69.4 ± 16.6 years; 329,107 (58.4%) were male. Mortality was 39,895 (7.1%). A total of 28,410 (5.0%) received ventilatory support during the hospital course, and 76.3% of nonsurvivors did not receive ventilatory support (62.6% of those aged <65 years and 78% of those aged ≥65 years). Higher age (relative risk (RR) 0.48, 95% confidence interval (CI) 0.44-0.51), failure to assess gas exchange (RR 0.18, 95% CI 0.14-0.25) and to administer antibiotics within 8 h of hospitalization (RR 0.48, 95% CI 0.39-0.59) were predictors of not receiving ventilatory support during hospitalization. Death from CAP occurred significantly earlier in the nonventilated group (8.2 ± 8.9 vs. 13.1 ± 14.1 days; p < 0.0001). The number of nonsurvivors without obvious reasons for withholding ventilatory support is disturbingly high, particularly in younger patients. Both performance predictors for not being ventilated remain ambiguous, because they may reflect either treatment restrictions or deficient clinical performance. Elucidating this ambiguity will be part of the forthcoming update of the quality assurance program.

Ventilatory and Physiological Responses in Swimmers Below and Above Their Maximal Lactate Steady State.

PubMed

Espada, Mario C; Reis, Joana F; Almeida, Tiago F; Bruno, Paula M; Vleck, Veronica E; Alves, Francisco B

2015-10-01

The purpose of this study was to understand the ventilatory and physiological responses immediately below and above the maximal lactate steady-state (MLSS) velocity and to determine the relationship of oxygen uptake (VO2) kinetics parameters with performance, in swimmers. Competitive athletes (N = 12) completed in random order and on different days a 400-m all-out test, an incremental step test comprising 5 × 250- and 1 × 200-m stages and 30 minutes at a constant swimming velocity (SV) at 87.5, 90, and 92.5% of the maximal aerobic velocity for MLSS velocity (MLSSv) determination. Two square-wave transitions of 500 m, 2.5% above and below the MLSSv were completed to determine VO2 on-kinetics. End-exercise VO2 at 97.5 and 102.5% of MLSSv represented, respectively, 81 and 97% of VO2max; the latter was not significantly different from maximal VO2 (VO2max). The VO2 at MLSSv (49.3 ± 9.2 ml·kg(-1)·min(-1)) was not significantly different from the second ventilatory threshold (VT2) (51.3 ± 7.6 ml·kg(-1)·min(-1)). The velocity associated with MLSS seems to be accurately estimated by the SV at VT2 (vVT2), and vVO2max also seems to be estimated with accuracy from the central 300-m mean velocity of a 400-m trial, indicators that represent a helpful tool for coaches. The 400-m swimming performance (T400) was correlated with the time constant of the primary phase VO2 kinetics (τp) at 97.5% MLSSv, and T800 was correlated with τp in both 97.5 and 102.5% of MLSSv. The assessment of the VO2 kinetics in swimming can help coaches to build training sets according to a swimmer's individual physiological response.

Effect of venous (gut) CO2 loading on intrapulmonary gas fractions and ventilation in the tegu lizard.

PubMed

Ballam, G O; Donaldson, L A

1988-01-01

Studies were conducted to determine regional pulmonary gas concentrations in the tegu lizard lung. Additionally, changes in pulmonary gas concentrations and ventilatory patterns caused by elevating venous levels of CO2 by gut infusion were measured. It was found that significant stratification of lung gases was present in the tegu and that dynamic fluctuations of CO2 concentration varied throughout the length of the lung. Mean FCO2 was greater and FO2 less in the posterior regions of the lung. In the posterior regions gas concentrations remained nearly constant, whereas in the anterior regions large swings were observed with each breath. In the most anterior sections of the lung near the bronchi, CO2 and O2 concentrations approached atmospheric levels during inspiration and posterior lung levels during expiration. During gut loading of CO2, the rate of rise of CO2 during the breathing pause increased. The mean level of CO2 also increased. Breathing rate and tidal volume increased to produce a doubling of VE. These results indicate that the method of introduction of CO2 into the tegu respiratory system determines the ventilatory response. If the CO2 is introduced into the venous blood a dramatic increase in ventilation is observed. If the CO2 is introduced into the inspired air a significant decrease in ventilation is produced. The changes in pulmonary CO2 environment caused by inspiratory CO2 loading are different from those caused by venous CO2 loading. We hypothesize that the differences in pulmonary CO2 environment caused by either inspiratory CO2 loading or fluctuations in venous CO2 concentration act differently on the IPC. The differing response of the IPC to the two methods of CO2 loading is the cause of the opposite ventilatory response seen during either venous or inspiratory loading.

Autonomic, functional, skeletal muscle, and cardiac abnormalities are associated with increased ergoreflex sensitivity in mitochondrial disease.

PubMed

Giannoni, Alberto; Aimo, Alberto; Mancuso, Michelangelo; Piepoli, Massimo Francesco; Orsucci, Daniele; Aquaro, Giovanni Donato; Barison, Andrea; De Marchi, Daniele; Taddei, Claudia; Cameli, Matteo; Raglianti, Valentina; Siciliano, Gabriele; Passino, Claudio; Emdin, Michele

2017-12-01

Mitochondrial disease (MD) is a genetic disorder affecting skeletal muscles, with possible myocardial disease. The ergoreflex, sensitive to skeletal muscle work, regulates ventilatory and autonomic responses to exercise. We hypothesized the presence of an increased ergoreflex sensitivity in MD patients, its association with abnormal ventilatory and autonomic responses, and possibly with subclinical cardiac involvement. Twenty-five MD patients (aged 46 ± 3 years, 32% male) with skeletal myopathy but without known cardiac disease, underwent a thorough evaluation including BNPs, galectin-3, soluble suppression of tumorigenesis 2 (sST2), high sensitivity troponin T/I, catecholamines, ECG, 24-h ECG recording, cardiopulmonary exercise testing, echocardiography, cardiac/muscle magnetic resonance (C/MMR), and ergoreflex assessment. Thirteen age- and sex-matched healthy controls were chosen. Among these myopathic patients, subclinical cardiac damage was detected in up to 80%, with 44% showing fibrosis at CMR. Ergoreflex sensitivity was markedly higher in patients than in controls (64% vs. 37%, P < 0.001), and correlated with muscle fat to water ratio and extracellular volume at MMR (both P < 0.05). Among patients, ergoreflex sensitivity was higher in those with cardiac involvement (P = 0.034). Patients showed a lower peak oxygen consumption (VO 2 /kg) than controls (P < 0.001), as well as ventilatory inefficiency (P = 0.024). Ergoreflex sensitivity correlated with reduced workload and peak VO 2 /kg (both P < 0.001), and several indicators of autonomic imbalance (P < 0.05). Plasma norepinephrine was the unique predictor of myocardial fibrosis at univariate analysis (P < 0.05). Skeletal myopathy in MD is characterized by enhanced ergoreflex sensitivity, which is associated with a higher incidence of cardiac involvement, exercise intolerance, and sympathetic activation. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Lower hypoxic ventilatory response in smokers compared to non-smokers during abstinence from cigarettes.

PubMed

Hildebrandt, Wulf; Sauer, Roland; Koehler, Ulrich; Bärtsch, Peter; Kinscherf, Ralf

2016-11-24

Carotid body O 2 -chemosensitivity determines the hypoxic ventilatory response (HVR) as part of crucial regulatory reflex within oxygen homeostasis. Nicotine has been suggested to attenuate HVR in neonates of smoking mothers. However, whether smoking affects HVR in adulthood has remained unclear and probably blurred by acute ventilatory stimulation through cigarette smoke. We hypothesized that HVR is substantially reduced in smokers when studied after an overnight abstinence from cigarettes i.e. after nicotine elimination. We therefore determined the isocapnic HVR of 23 healthy male smokers (age 33.9 ± 2.0 years, BMI 24.2 ± 0.5 kg m -2 , mean ± SEM) with a smoking history of >8 years after 12 h of abstinence and compared it to that of 23 healthy male non-smokers matched for age and BMI. Smokers and non-smokers were comparable with regard to factors known to affect isocapnic HVR such as plasma levels of glucose and thiols as well as intracellular levels of glutathione in blood mononuclear cells. As a new finding, abstinent smokers had a significantly lower isocapnic HVR (0.024 ± 0.002 vs. 0.037 ± 0.003 l min -1 % -1 BMI -1 , P = 0.002) compared to non-smokers. However, upon re-exposure to cigarettes the smokers' HVR increased immediately to the non-smokers' level. This is the first report of a substantial HVR reduction in abstinent adult smokers which appears to be masked by daily smoking routine and may therefore have been previously overlooked. A low HVR may be suggested as a novel link between smoking and aggravated hypoxemia during sleep especially in relevant clinical conditions such as COPD.

The Gravity-Loading countermeasure Skinsuit (GLCS) and its effect upon aerobic exercise performance

NASA Astrophysics Data System (ADS)

Attias, Julia; Philip, A. T. Carvil; Waldie, James; Russomano, Thais; Simon, N. Evetts; David, A. Green

2017-03-01

The Russian Pingvin suit is employed as a countermeasure to musculoskeletal atrophy in microgravity, though its 2-stage loading regime is poorly tolerated. The Gravity-Loading Countermeasure Skinsuit (GLCS) has been devised to comfortably compress the body via incrementally increasing longitudinal elastic-fibre tensions from the shoulders to the feet. We tested whether the Mk III GLCS was a feasible adjunct to sub-maximal aerobic exercise and resulting VO2Max predictions. Eight healthy subjects (5♂, 28±6 yr) performed cycle ergometry at 75% VO2Max (derived from an Astrand-Rhyming protocol) whilst wearing a GLCS and gym clothing (GYM). Ventilatory parameters, heart rate (HR), core temperature (TC), and blood lactate (BL) were recorded along with subjective perceived exertion, thermal comfort, movement discomfort and body control. Physiological and subjective responses were compared over TIME and between GYM and GLCS (ATTIRE) with 2-way repeated measures ANOVA and Wilcoxon tests respectively. Resultant VO2Max predictions were compared with paired t-tests between ATTIRE. The GLCS induced greater initial exercise ventilatory responses which stabilised by 20 min. HR and TC continued to rise from 5 min irrespective of ATTIRE, whereas BL was greater in the GLCS at 20 min. Predicted V O2Max did not differ with ATTIRE, though some observed differences in HR were noteworthy. All subjective ratings were exacerbated in the GLCS. Despite increased perception of workload and initial ventilatory augmentations, submaximal exercise performance was not impeded. Whilst predicted VO2Max did not differ, determination of actual VO2Max in the GLCS is warranted due to apparent modulation of the linear HR-VO2 relationship. The GLCS may be a feasible adjunct to exercise and potential countermeasure to unloaded-induced physiological deconditioning on Earth or in space.

Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives.

PubMed

Brutsaert, Tom D; Parra, Esteban J; Shriver, Mark D; Gamboa, Alfredo; Rivera-Ch, Maria; León-Velarde, Fabiola

2005-07-01

Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.

[Individual-typological evaluation of cardiorespiratory responses to hypoxia and hypercapnia in young healthy men].

PubMed

Divert, V E; Krivoshchekov, S G; Vodyanitsky, S N

2015-01-01

The aim of the study was the approaches development to a substantiation of recommendations on the persons selection for different types of physical exercise on the basis of individual chemoreflex reactivity of cardiorespiratory system. That's for the ventilatory and cardial responses in tests with increasing inhalation hypoxia and hypercapnia on the group of young healthy man was performed. It was shown that hypoxia induce predominantly cardial response, but hypercapnia--ventilatory response. On that predominantly chemoreflex reactions (respiration system to hypercarbia and cardiac--to hypoxaemia) four types of in parts were defined: small reactions in both parts (type 1), small reaction of cardiac system and strong of respiratory system (type 2), strong for heart response and small for respiration (type 3), and strong for both parts (type 4). Statistical analysis has shown that each type of reactions is specific to certain kind of sports training: 1 type for swimmers, 2 and 3 types for skiers, 4 type for boxers, weight lifters and wrestlers. For skiers group the inverse regression dependence between the growth of heart reactivity to hypoxaemia and depression of the pulmonary ventilation reactivity to hypercarbia is revealed at joint rising of the oxygen consumption per unit body weight. High quality skiers are distinguished by relative balance of chemoreflex responses of respiration and heart. It was found that physically untrained persons have pronounced individual variability of cardiorespiratory system chemoreflex reactions, what can be used for personal recommendations for choosing the kind of sports to employment.

[The changes of physiological reactivity of cardiorespiratory system to respiratory homeostasis with the use of complex stimulation of special work capacity].

PubMed

Lysenko, O M

2012-01-01

We present the influence of the program of special additional stimulation of work capacity of high-performance athletes on the sensitivity of cardiorespiratory system to hypercapnic and hypoxic shifts in respiratory homeostasis. We found that under the influence of the pre-start complex a decrease in the sensitivity of ventilator responses to CO2-H+ stimuli in combination with a reduction in the thresholds of the reaction take place. This creates conditions for increased mobilization properties of the cardiorespiratory system and economization of its reaction under conditions of changes of respiratory homeostasis characteristic of intense training and competitive loads in the sport.

Spirometric evaluation of ventilatory function in adult male cigarette smokers in Sokoto metropolis.

PubMed

Isah, Muhammad D; Makusidi, Muhammad A; Abbas, Aminu; Okpapi, Juliana U; Njoku, Chibueze H; Abba, Abdullahi A

2017-01-01

Cigarette smoking is a widespread social habit in Nigeria with extensive deleterious multisystemic effect. Ventilatory dysfunction is one of the cigarette smoking-related illnesses that affect the respiratory system. Spirometry is an investigative method that can be used for the early detection of ventilatory dysfunction even before the onset of the symptoms. A questionnaire adapted from the European Community Respiratory Health Survey was administered to collect demographic, clinical, and cigarette smoking data. Ventilatory function test was conducted using Clement Clarke (One Flow) Spirometer, version 1.3. The highest value of each ventilatory function index was chosen for analysis, and individual(s) with ventilatory dysfunction were subjected to post bronchodilator spirometry. For the purpose of this research, 150 participants who were currently cigarette smokers were enrolled, and 50 apparently healthy, age-matched individuals who were never smokers served as controls in the ratio of 3:1. Eighty percent of participants and 68% of controls were aged 40 years or below. The mean age of participants (34.27 ± 8.91 years) and the controls (35.08 ± 10.35 years) was not significantly different (P = 0.592). Similarly, there were no statistically significant differences between the mean anthropometric indices (weight: P = 0.663, height: P = 0.084, and body mass index: P = 0.099) of both participants and controls. The mean values of FEV1 (forced expiratory flow in one second) and FEV1/FVC (FVC=forced vital capacity) were lower in the participants compared to the controls, and this difference was statistically significant (P < 0.001). There was a weak negative correlation between pack-years of cigarette smoking and FEV1 (r = -0.237 and P = 0.004). Obstructive ventilatory defect was found among six study participants (4%) and two controls (4%). Cigarette smoking is associated with decline in ventilatory function test indices (FEV1 and FEV1/FVC) in adult males. Decline in FEV1 is directly related to pack-years of cigarette smoking.

Anterior cerebral blood velocity and end-tidal CO2 responses to exercise differ in children and adults.

PubMed

Ellis, Lindsay A; Ainslie, Philip N; Armstrong, Victoria A; Morris, Laura E; Simair, Ryan G; Sletten, Nathan R; Tallon, Christine M; McManus, Ali M

2017-06-01

Little is known about the response of the cerebrovasculature to acute exercise in children and how these responses might differ with adults. Therefore, we compared changes in middle cerebral artery blood velocity (MCAV mean ), end-tidal Pco 2 ([Formula: see text]), blood pressure, and minute ventilation (V̇e) in response to incremental exercise between children and adults. Thirteen children [age: 9 ± 1 (SD) yr] and thirteen sex-matched adults (age: 25 ± 4 yr) completed a maximal exercise test, during which MCAV mean , [Formula: see text], and V̇e were measured continuously. These variables were measured at rest, at exercise intensities specific to individual ventilatory thresholds, and at maximum. Although MCAV mean was higher at rest in children compared with adults, there were smaller increases in children (1-12%) compared with adults (12-25%) at all exercise intensities. There were alterations in [Formula: see text] with exercise intensity in an age-dependent manner [ F (2.5,54.5) = 7.983, P < 0.001; η 2 = 0.266], remaining stable in children with increasing exercise intensity (37-39 mmHg; P > 0.05) until hyperventilation-induced reductions following the respiratory compensation point. In adults, [Formula: see text] increased with exercise intensity (36-45 mmHg, P < 0.05) until the ventilatory threshold. From the ventilatory threshold to maximum, adults showed a greater hyperventilation-induced hypocapnia than children. These findings show that the relative increase in MCAV mean during exercise was attenuated in children compared with adults. There was also a weaker relationship between MCAV mean and [Formula: see text] during exercise in children, suggesting that cerebral perfusion may be regulated by different mechanisms during exercise in the child. NEW & NOTEWORTHY These findings provide the first direct evidence that exercise increases cerebral blood flow in children to a lesser extent than in adults. Changes in end-tidal CO 2 parallel changes in cerebral perfusion in adults but not in children, suggesting age-dependent regulatory mechanisms of cerebral blood flow during exercise. Copyright © 2017 the American Physiological Society.

Effects of Pregnancy on Responses to Exercise Above and Below the Ventilatory Anaerobic THreshold

DTIC Science & Technology

1999-10-01

815-827, 1998. Chapers in Books Wolfe, L.A. and M.F. Mottola. Chapter on Pregnacy In: (D. Kumbhare and J.V Basmajian, Eds.). Clinical Decision Makinq...effects of All and AVP may be more easily identified in early pregnacy when progesterone levels are relatively low. Further study is recommended to

CO[subscript 2] Rebreathing: An Undergraduate Laboratory to Study the Chemical Control of Breathing

ERIC Educational Resources Information Center

Domnik, N. J.; Turcotte, S. E.; Yuen, N. Y.; Iscoe, S.; Fisher, J. T.

2013-01-01

The Read CO[subscript]2 rebreathing method (Read DJ. "A clinical method for assessing the ventilatory response to carbon dioxide." "Australas Ann Med" 16: 20-32, 1967) provides a simple and reproducible approach for studying the chemical control of breathing. It has been widely used since the modifications made by Duffin and…

Optimization behavior of brainstem respiratory neurons. A cerebral neural network model.

PubMed

Poon, C S

1991-01-01

A recent model of respiratory control suggested that the steady-state respiratory responses to CO2 and exercise may be governed by an optimal control law in the brainstem respiratory neurons. It was not certain, however, whether such complex optimization behavior could be accomplished by a realistic biological neural network. To test this hypothesis, we developed a hybrid computer-neural model in which the dynamics of the lung, brain and other tissue compartments were simulated on a digital computer. Mimicking the "controller" was a human subject who pedalled on a bicycle with varying speed (analog of ventilatory output) with a view to minimize an analog signal of the total cost of breathing (chemical and mechanical) which was computed interactively and displayed on an oscilloscope. In this manner, the visuomotor cortex served as a proxy (homolog) of the brainstem respiratory neurons in the model. Results in 4 subjects showed a linear steady-state ventilatory CO2 response to arterial PCO2 during simulated CO2 inhalation and a nearly isocapnic steady-state response during simulated exercise. Thus, neural optimization is a plausible mechanism for respiratory control during exercise and can be achieved by a neural network with cognitive computational ability without the need for an exercise stimulus.

[Hemoglobin and testosterone: importance on high altitude acclimatization and adaptation].

PubMed

Gonzales, Gustavo F

2011-03-01

The different types of response mechanisms that the organism uses when exposed to hypoxia include accommodation, acclimatization and adaptation. Accommodation is the initial response to acute exposure to high altitude hypoxia and is characterized by an increase in ventilation and heart rate. Acclimatization is observed in individuals temporarily exposed to high altitude, and to some extent, it enables them to tolerate the high altitudes. In this phase, erythropoiesis is increased, resulting in higher hemoglobin and hematocrit levels to improve oxygen delivery capacity. Adaptation is the process of natural acclimatization where genetical variations and acclimatization play a role in allowing subjects to live without any difficulties at high altitudes. Testosterone is a hormone that regulates erythropoiesis and ventilation and could be associated to the processes of acclimatization and adaptation to high altitude. Excessive erythrocytosis, which leads to chronic mountain sickness, is caused by low arterial oxygen saturation, ventilatory inefficiency and reduced ventilatory response to hypoxia. Testosterone increases during acute exposure to high altitude and also in natives at high altitude with excessive erythrocytosis. Results of current research allow us to conclude that increase in serum testosterone and hemoglobin is adequate for acclimatization, as they improve oxygen transport, but not for high altitude adaptation, since high serum testosterone levels are associated to excessive erythrocytosis.

Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats.

PubMed

Hodges, Matthew R; Echert, Ashley E; Puissant, Madeleine M; Mouradian, Gary C

2013-04-01

The Brown Norway (BN; BN/NHsdMcwi) rat exhibits a deficit in ventilatory CO2 sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO2 sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7% CO2 exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10mg/(kgday)) in adult male BN and SD rats. Fluoxetine had minimal effects on room air breathing in BN and SD rats (p>0.05), although tidal volume (VT) was reduced in BN rats (p<0.05). There were also minimal effects of fluoxetine on CO2 sensitivity in SD rats, but fluoxetine increased minute ventilation, breathing frequency and VT during hypercapnia in BN rats (p<0.05). The augmented CO2 response was reversible upon withdrawal of fluoxetine. Brain levels of biogenic amines were largely unaffected, but 5-HIAA and the ratio of 5-HIAA/5-HT were reduced (p<0.05) consistent with selective and effective 5-HT reuptake inhibition. Thus, fluoxetine increases ventilatory CO2 sensitivity in BN but not SD rats, further suggesting altered 5-HT system function may contribute to the inherently low CO2 sensitivity in the BN rat. Copyright © 2013 Elsevier B.V. All rights reserved.

Hypopnea consequent to reduced pulmonary blood flow in the dog.

PubMed

Stremel, R W; Whipp, B J; Casaburi, R; Huntsman, D J; Wasserman, K

1979-06-01

The ventilatory responses to diminished pulmonary blood flow (Qc), as a result of partial cardiopulmonary bypass (PCB), were studied in chloralose-urethan-anesthetized dogs. Qc was reduced by diverting vena caval blood through a membrane gas exchanger and returning it to the ascending aorta. PCB flows of 400--1,600 ml/min were utilized for durations of 2--3 min. Decreasing Qc, while maintaining systemic arterial blood gases and perfusion, results in a significant (P less than 0.05) decrease in expiratory ventilation (VE) (15.9%) and alveolar ventilation (VA) (31.0%). The ventilatory decreases demonstrated for this intact group persist after bilateral cervical vagotomy (Vx), carotid body and carotid sinus denervation (Cx), and combined Vx and Cx. The changes in VE and VA were significantly (P less than 0.001) correlated with VCO2 changes, r = 0.80 and r = 0.93, respectively. These ventilatory changes were associated with an overall average decrease in left ventricular PCO2 of 2.1 Torr; this decrease was significant (P less than 0.05) only in the intact and Cx groups. Decreasing pulmonary blood flow results in a decrease in ventilation that may be CO2 related; however, the exact mechanism remains obscure but must have a component that is independent of vagally mediated cardiac and pulmonary afferents and peripheral baroreceptor and chemoreceptor afferents.

Ventilatory parameters and maximal respiratory pressure changes with age in Duchenne muscular dystrophy patients.

PubMed

Gayraud, Jerome; Ramonatxo, Michele; Rivier, François; Humberclaude, Véronique; Petrof, Basil; Matecki, Stefan

2010-06-01

The aim of this longitudinal study was to precise, in children with Duchenne muscular dystrophy, the respective functional interest of ventilatory parameters (Vital capacity, total lung capacity and forced expiratory volume in one second [FEV(1)]) in comparison to maximal inspiratory pressure (Pimax) during growth. In ten boys the mean age of 9.1 +/- 1 years) to mean age of 16 +/- 1.4 years followed over a period of 7 years, we found that: (1) ventilatory parameters expressed in percentage of predicted value, after a normal ascending phase, start to decrease between 11 and 12 years, (2) Pimax presented only a decreasing phase since the beginning of the study and thus was already at 67% of predicted value at 12 years while ventilatory parameters was still normal, (3) after 12 years the mean slopes of decrease per year of vital capacity and FEV1 were higher (10.7 and 10.4%) than that of Pimax (6.9%), (4) at 15 years mean values of vital capacity and FEV1 (53.3 and 49.5% of predicted values) was simlar to that of Pimax (48.3%). In conclusion, if at early stages of the disease, Pimax is a more reliable index of respiratory impaiment than ventilatory parameters, the follow-up of ventilatory parameters, when they start to decrease, is a better indicator of disease progression and, at advanced stages they provided same information about the functional impact of disease.

Gas exchange and ventilation during dormancy in the tegu lizard tupinambis merianae

PubMed

de Andrade DV; Abe

1999-12-01

The tegu lizard Tupinambis merianae exhibits an episodic ventilatory pattern when dormant at 17 degrees C but a uniform ventilatory pattern when dormant at 25 degrees C. At 17 degrees C, ventilatory episodes were composed of 1-22 breaths interspaced by non-ventilatory periods lasting 1.8-26 min. Dormancy at the higher body temperature was accompanied by higher rates of O(2) consumption and ventilation. The increase in ventilation was due only to increases in breathing frequency with no change observed in tidal volume. The air convection requirement for O(2) did not differ at the two body temperatures. The respiratory quotient was 0.8 at 17 degrees C and 1.0 at 25 degrees C. We found no consistent relationship between expired gas composition and the start/end of the ventilatory period during episodic breathing at 17 degrees C. However, following non-ventilatory periods of increasing duration, there was an increase in the pulmonary O(2) extraction that was not coupled to an equivalent increase in elimination of CO(2) from the lungs. None of the changes in the variables studied could alone explain the initiation/termination of episodic ventilation in the tegus, suggesting that breathing episodes are shaped by a complex interaction between many variables. The estimated oxidative cost of breathing in dormant tegus at 17 degrees C was equivalent to 52.3 % of the total metabolic rate, indicating that breathing is the most costly activity during dormancy.

[Relation between ultrasound-measured diaphragm movement and partial pressure of carbon dioxide in blood from patients with acute hypercapnic respiratory failure after the start of noninvasive ventilation in an emergency department].

PubMed

Sánchez-Nicolás, José Andrés; Cinesi-Gómez, César; Villén-Villegas, Tomás; Piñera-Salmerón, Pascual; García-Pérez, Bartolo

2016-10-01

To evaluate the correlation between variations in ultrasound-measured diaphragm movement and changes in the arterial partial pressure of carbon dioxide (PCO2) after the start of noninvasive ventilation (NIV). RDescriptive study of a prospective case series comprised of nonconsecutive patients aged 18 years or older with hypercapnic respiratory failure who were placed on NIV in an emergency department. We recorded clinical data, blood gas measurements, and ultrasound measurements of diaphragm movement. Twenty-one patients with a mean (SD) age of 83 (13) years were studied; 11 (52.4%) were women. The mean (SD) range of diaphragm movement and PCO2 values at 4 moments were as follows: 1) at baseline: diaphragm movement, 13.90 (7.7) mm and PCO2, 71.75 (11.4) mm Hg; 2) after 15 minutes on NIV: diaphragm movement, 17.10 (9.1) mm; 3) at 1 hour: diaphragm movement, 22.40 (10.4) mm and PCO2, 63.45 (16.0) mm Hg; and 4) at 3 hours: diaphragm movement, 26.60 (19.5) mm and PCO2, 61.85 (13.0) mm Hg. We detected a statistically significant correlation between the difference in range of diaphragm movement at baseline and at 15 minutes and the decrease in PCO2 after 1 hour of NIV (r=-0.489, P=.035). In patients with hypercapnic respiratory failure, the increase in range of diaphragm movement 15 minutes after starting NIV is associated with a decrease in PCO2 after 1 hour.

The Chinese version of the Severe Respiratory Insufficiency questionnaire for patients with chronic hypercapnic chronic obstructive pulmonary disease receiving non-invasive positive pressure ventilation.

PubMed

Chen, Rongchang; Guan, Lili; Wu, Weiliang; Yang, Zhicong; Li, Xiaoying; Luo, Qun; Liang, Zhenyu; Wang, Fengyan; Guo, Bingpeng; Huo, Yating; Yang, Yuqiong; Zhou, Luqian

2017-08-28

The Severe Respiratory Insufficiency (SRI) questionnaire is the best assessment tool for health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) receiving non-invasive positive pressure ventilation (NIPPV). This study aimed to translate the SRI Questionnaire into Chinese and to validate it. Prospective validation study. A total of 149 participants with chronic hypercapnic COPD receiving NIPPV completed the study. The SRI questionnaire was translated into Chinese using translation and back-translation. Reliability was gauged using Cronbach's α coefficient. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess construct validity. Content validity was confirmed by evaluating the relationship between the score of each item and the total score of the relevant subscale. Cronbach's α coefficients for each subscale and summary scale were above 0.7. Using EFA, one factor was extracted from the anxiety and summary scales and two factors were extracted from the remaining six subscales. Based on the EFA results, subsequent CFA revealed a good model fit for each subscale, but the extracted factors of each subscale were correlated. Content validity was confirmed by the good relationship between the score of each item and the total score of the relevant subscale. The Chinese version of the SRI questionnaire is valid and reliable for patients with chronic hypercapnic COPD receiving NIPPV in China. NCT02499718. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Home noninvasive positive pressure ventilation with built-in software in stable hypercapnic COPD: a short-term prospective, multicenter, randomized, controlled trial.

PubMed

Zhou, Luqian; Li, Xiaoying; Guan, Lili; Chen, Jianhua; Guo, Bingpeng; Wu, Weiliang; Huo, Yating; Zhou, Ziqing; Liang, Zhenyu; Zhou, Yuqi; Tan, Jie; Chen, Xin; Song, Yuanlin; Chen, Rongchang

2017-01-01

The benefits of noninvasive positive pressure ventilation (NPPV) in patients with hypercapnic COPD are controversial. It is presumed that methodology and appropriate use of NIV ventilator might be crucial for the outcomes. With the new built-in software, the performance of NIV can be monitored at home, which can guarantee the compliance and appropriate use. This study investigated effects of home use of NIV in hypercapnia in COPD patients using the NIV ventilator with built-in software for monitoring. The current multicenter prospective, randomized, controlled trial enrolled patients with stable GOLD stages III and IV hypercapnic COPD. Patients were randomly assigned via a computer-generated randomization sequence, with a block size of four patients, to continue optimized treatment (control group) or to receive additional NPPV (intervention group) for 3 months. The primary outcome was arterial carbon dioxide pressure (PaCO 2 ). Data were derived from built-in software and analyzed every 4 weeks. Analysis was carried out with the intention to treat. This study is registered with ClinicalTrials.gov, number NCT02499718. Patients were recruited from 20 respiratory units in China from October 1, 2015, and recruitment was terminated with a record of the vital statistics on May 31, 2016. A total of 115 patients were randomly assigned to the NPPV group (n=57) or the control group (n=58). Patients complied well with NPPV therapy (mean [± standard deviation] day use 5.6±1.4 h). The mean estimation of leaks was 37.99±13.71 L/min. The changes in PaCO 2 (-10.41±0.97 vs -4.32±0.68 mmHg, P =0.03) and 6-min walk distance (6MWD) (38.2% vs 18.2%, P =0.02) were statistically significant in the NPPV group versus the control group. COPD assessment test (CAT) showed a positive trend ( P =0.06) in favor of the NPPV group. Pulmonary function and dyspnea were not different between groups. Ventilators equipped with built-in software provided methodology for monitoring NIV use at home, which could facilitate the improvement of compliance and quality control of NIV use. It was shown that three months use of NIV at home could reduce the PaCO 2 and improve exercise tolerance (6MWD) in chronic hypercapnic COPD patients.

Treatment of obesity hypoventilation syndrome and serum leptin.

PubMed

Yee, Brendon J; Cheung, Jane; Phipps, Paul; Banerjee, Dev; Piper, Amanda J; Grunstein, Ronald R

2006-01-01

Leptin is a protein produced by adipose tissue that circulates to the brain and interacts with receptors in the hypothalamus to inhibit eating. In obese humans, serum leptin is up to four times higher than in lean subjects, indicating that human obesity is associated with a central resistance to the weight-lowering effects of leptin. Although the leptin-deficient mouse (ob/ob) develops obesity hypoventilation syndrome (OHS), in humans with OHS, serum leptin is a better predictor of awake hypercapnia in obesity than the body mass index (BMI). This suggests that central leptin resistance may promote the development of OHS in humans. We speculated that the reversal of OHS by regular non-invasive ventilation (NIV) therapy decreases leptin levels. The aim of this study was to investigate whether ventilatory treatment of OHS would alter circulating leptin concentrations. We measured fasting serum leptin levels, BMI, spirometry and arterial blood gases in 14 obese hypercapnic subjects undergoing a diagnostic sleep study. The average age of the subjects was (mean +/- SE) 62 +/- 13 years, BMI 40.9 +/- 2.2 kg/m(2), PaCO(2) 6.7 +/- 0.2 kPa, PaO(2 )8.9 +/- 0.4 kPa and total respiratory disturbance index 44 +/- 35 events/hour. Subjects were clinically reviewed after a median of 2.3 years (range 1.6-3) with repeat investigations. Nine patients were regular NIV users and 5 were non-users. NIV users had a significant reduction in serum leptin levels (p = 0.001), without a change in BMI. In these patients, there was a trend towards an improved daytime hypercapnia and hypoxemia, while in the 5 non-users, no changes in serum leptin, BMI or arterial blood gases occurred. Regular NIV use reduces serum leptin in OHS. Leptin may be a modulator of respiratory drive in patients with OHS.

NIV by an interdisciplinary respiratory care team in severe respiratory failure in the emergency department limited to day time hours.

PubMed

Horvath, Christian Michael; Brutsche, Martin Hugo; Schoch, Otto Dagobert; Schillig, Bernarde; Baty, Florent; vonOw, Dieter; Rüdiger, Jochen Julius

2017-12-01

Non-invasive ventilatory support is frequently used in patients with severe respiratory failure (SRF), but is often limited to intensive care units (ICU). We hypothesized that an instantaneous short course of NIV (up to 2 h), limited to regular working hours as an additional therapy on the emergency department (ED) would be feasible and could improve patient´s dyspnoea measured by respiratory rate and Borg visual dyspnea scale. NIV was set up by an interdisciplinary respiratory care team. Outside these predefined hours NIV was performed in the ICU. This is an observational cohort study over 1 year in the ED in a non-university hospital. Fifty-one % of medical emergencies arrived during regular working hours (5475 of 10,718 patients). In total, 63 patients were treated with instantaneous NIV. Door to NIV in the ED was 56 (31-97) min, door to ICU outside regular working hours was 84 (57-166) min. Within 1 h of NIV, the respiratory rate decreased from 30/min (25-35) to 19/min (14-24, p < 0.001), the Borg dyspnoea scale improved from 7 (5-8) to 2 (0-3, p < 0.001). In hypercapnic patients, the blood-pH increased from 7.29 (7.24-7.33) to 7.35 (7.29-7.40) and the pCO 2 dropped from 8.82 (8.13-10.15) to 7.45 (6.60-8.75) kPa. In patients with SRF of varying origin, instantaneous NIV in the ED during regular working hours was feasible in a non-university hospital setting, and rapidly and significantly alleviated dyspnoea and reduced respiratory rate. This approach proved to be useful as a bridge to the ICU as well as an efficient palliative dyspnoea treatment.

Cerebrovascular reactivity is increased with acclimatization to 3,454 m altitude.

PubMed

Flück, Daniela; Siebenmann, Christoph; Keiser, Stefanie; Cathomen, Adrian; Lundby, Carsten

2015-08-01

Controversy exists regarding the effect of high-altitude exposure on cerebrovascular CO2 reactivity (CVR). Confounding factors in previous studies include the use of different experimental approaches, ascent profiles, duration and severity of exposure and plausibly environmental factors associated with altitude exposure. One aim of the present study was to determine CVR throughout acclimatization to high altitude when controlling for these. Middle cerebral artery mean velocity (MCAv mean) CVR was assessed during hyperventilation (hypocapnia) and CO2 administration (hypercapnia) with background normoxia (sea level (SL)) and hypoxia (3,454 m) in nine healthy volunteers (26 ± 4 years (mean ± s.d.)) at SL, and after 30 minutes (HA0), 3 (HA3) and 22 (HA22) days of high-altitude (3,454 m) exposure. At altitude, ventilation was increased whereas MCAv mean was not altered. Hypercapnic CVR was decreased at HA0 (1.16% ± 0.16%/mm Hg, mean ± s.e.m.), whereas both hyper- and hypocapnic CVR were increased at HA3 (3.13% ± 0.18% and 2.96% ± 0.10%/mm Hg) and HA22 (3.32% ± 0.12% and 3.24% ± 0.14%/mm Hg) compared with SL (1.98% ± 0.22% and 2.38% ± 0.10%/mm Hg; P < 0.01) regardless of background oxygenation. Cerebrovascular conductance (MCAv mean/mean arterial pressure) CVR was determined to account for blood pressure changes and revealed an attenuated response. Collectively our results show that hypocapnic and hypercapnic CVR are both elevated with acclimatization to high altitude.

Cerebrovascular reactivity is increased with acclimatization to 3,454 m altitude

PubMed Central

Flück, Daniela; Siebenmann, Christoph; Keiser, Stefanie; Cathomen, Adrian; Lundby, Carsten

2015-01-01

Controversy exists regarding the effect of high-altitude exposure on cerebrovascular CO2 reactivity (CVR). Confounding factors in previous studies include the use of different experimental approaches, ascent profiles, duration and severity of exposure and plausibly environmental factors associated with altitude exposure. One aim of the present study was to determine CVR throughout acclimatization to high altitude when controlling for these. Middle cerebral artery mean velocity (MCAvmean) CVR was assessed during hyperventilation (hypocapnia) and CO2 administration (hypercapnia) with background normoxia (sea level (SL)) and hypoxia (3,454 m) in nine healthy volunteers (26±4 years (mean±s.d.)) at SL, and after 30 minutes (HA0), 3 (HA3) and 22 (HA22) days of high-altitude (3,454 m) exposure. At altitude, ventilation was increased whereas MCAvmean was not altered. Hypercapnic CVR was decreased at HA0 (1.16%±0.16%/mm Hg, mean±s.e.m.), whereas both hyper- and hypocapnic CVR were increased at HA3 (3.13%±0.18% and 2.96%±0.10%/mm Hg) and HA22 (3.32%±0.12% and 3.24%±0.14%/mm Hg) compared with SL (1.98%±0.22% and 2.38%±0.10%/mm Hg; P<0.01) regardless of background oxygenation. Cerebrovascular conductance (MCAvmean/mean arterial pressure) CVR was determined to account for blood pressure changes and revealed an attenuated response. Collectively our results show that hypocapnic and hypercapnic CVR are both elevated with acclimatization to high altitude. PMID:25806704

Delayed but successful response to noninvasive ventilation in COPD patients with acute hypercapnic respiratory failure.

PubMed

Lemyze, Malcolm; Bury, Quentin; Guiot, Aurélie; Jonard, Marie; Mohammad, Usman; Van Grunderbeeck, Nicolas; Gasan, Gaelle; Thevenin, Didier; Mallat, Jihad

2017-01-01

We evaluated a new noninvasive ventilation (NIV) protocol that allows the pursuit of NIV in the case of persistent severe respiratory acidosis despite a first NIV challenge in COPD patients with acute hypercapnic respiratory failure (AHRF). A prospective observational multicentric pilot study was conducted in three tertiary hospitals over a 12-month study period. A total of 155 consecutive COPD patients who were admitted for AHRF and treated by NIV were enrolled. Delayed response to NIV was defined as a significant clinical improvement in the first 48 h following NIV initiation despite a persistent severe respiratory acidosis (pH <7.30) after the first 2 h of NIV trial. NIV failed in only 10 patients (6.5%). Delayed responders to NIV (n=83, 53%) exhibited similar nutritional status, comorbidities, functional status, frailty score, dyspnea score, and severity score at admission, compared with early responders (n=62, 40%). Only age (66 vs 70 years in early responders; P =0.03) and encephalopathy score (3 [2-4] vs 3 [2-4] in early responders; P =0.015) were different among the responders. Inhospital mortality did not differ between responders to NIV (n=10, 12% for delayed responders vs n=10, 16% for early responders, P =0.49). A second episode of AHRF occurred in 20 responders (14%), equally distributed among early and delayed responders to NIV (n=9, 14.5% in early responders vs n=11, 13% in delayed responders; P =0.83), with a poor survival rate (n=1, 5%). Most of the COPD patients with AHRF have a successful outcome when NIV is pursued despite a persistent severe respiratory acidosis after the first NIV trial. The outcome of delayed responders is similar to the one of the early responders. On the contrary, the second episode of AHRF during the hospital stay carries a poor prognosis.

Cerebrovascular regulation in men and women: stimulus-specific role of cyclooxygenase.

PubMed

Peltonen, Garrett L; Harrell, John W; Rousseau, Cameron L; Ernst, Brady S; Marino, Mariah L; Crain, Meghan K; Schrage, William G

2015-07-01

Greater cerebral artery vasodilation mediated by cyclooxygenase (COX) in female animals is unexplored in humans. We hypothesized that young, healthy women would exhibit greater basal cerebral blood flow (CBF) and greater vasodilation during hypoxia or hypercapnia compared to men, mediated by a larger contribution of COX. We measured middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) in 42 adults (24 women, 18 men; 24 ± 1 years) during two visits, in a double-blind, placebo-controlled design (COX inhibition, 100 mg oral indomethacin, Indo). Women were studied early in the follicular phase of the menstrual cycle (days 1-5). Two levels of isocapnic hypoxia (SPO2 = 90% and 80%) were induced for 5-min each. Separately, hypercapnia was induced by increasing end-tidal carbon dioxide (PETCO 2) 10 mmHg above baseline. A positive change in MCAv (ΔMCAv) reflected vasodilation. Basal MCAv was greater in women compared to men (P < 0.01) across all conditions. Indo decreased baseline MCAv (P < 0.01) similarly between sexes. Hypoxia increased MCAv (P < 0.01), but ΔMCAv was not different between sexes. Indo did not alter hypoxic vasodilation in either sex. Hypercapnia increased MCAv (P < 0.01), but ΔMCAv was not different between sexes. Indo elicited a large decrease in hypercapnic vasodilation (P < 0.01) that was similar between sexes. During the early follicular phase, women exhibit greater basal CBF than men, but similar vasodilatory responses to hypoxia and hypercapnia. Moreover, COX is not obligatory for hypoxic vasodilation, but plays a vital and similar role in the regulation of basal CBF (~30%) and hypercapnic response (~55%) between sexes. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Understanding nurses' decision-making when managing weaning from mechanical ventilation: a study of novice and experienced critical care nurses in Scotland and Greece.

PubMed

Kydonaki, Kalliopi; Huby, Guro; Tocher, Jennifer; Aitken, Leanne M

2016-02-01

To examine how nurses collect and use cues from respiratory assessment to inform their decisions as they wean patients from ventilatory support. Prompt and accurate identification of the patient's ability to sustain reduction of ventilatory support has the potential to increase the likelihood of successful weaning. Nurses' information processing during the weaning from mechanical ventilation has not been well-described. A descriptive ethnographic study exploring critical care nurses' decision-making processes when weaning mechanically ventilated patients from ventilatory support in the real setting. Novice and expert Scottish and Greek nurses from two tertiary intensive care units were observed in real practice of weaning mechanical ventilation and were invited to participate in reflective interviews near the end of their shift. Data were analysed thematically using concept maps based on information processing theory. Ethics approval and informed consent were obtained. Scottish and Greek critical care nurses acquired patient-centred objective physiological and subjective information from respiratory assessment and previous knowledge of the patient, which they clustered around seven concepts descriptive of the patient's ability to wean. Less experienced nurses required more encounters of cues to attain the concepts with certainty. Subjective criteria were intuitively derived from previous knowledge of patients' responses to changes of ventilatory support. All nurses used focusing decision-making strategies to select and group cues in order to categorise information with certainty and reduce the mental strain of the decision task. Nurses used patient-centred information to make a judgment about the patients' ability to wean. Decision-making strategies that involve categorisation of patient-centred information can be taught in bespoke educational programmes for mechanical ventilation and weaning. Advanced clinical reasoning skills and accurate detection of cues in respiratory assessment by critical care nurses will ensure optimum patient management in weaning mechanical ventilation. © 2016 John Wiley & Sons Ltd.

Adaptation of exercise ventilation during an actively-induced hyperthermia following passive heat acclimation.

PubMed

Beaudin, Andrew E; Clegg, Miriam E; Walsh, Michael L; White, Matthew D

2009-09-01

Hyperthermia-induced hyperventilation has been proposed to be a human thermolytic thermoregulatory response and to contribute to the disproportionate increase in exercise ventilation (VE) relative to metabolic needs during high-intensity exercise. In this study it was hypothesized that VE would adapt similar to human eccrine sweating (E(SW)) following a passive heat acclimation (HA). All participants performed an incremental exercise test on a cycle ergometer from rest to exhaustion before and after a 10-day passive exposure for 2 h/day to either 50 degrees C and 20% relative humidity (RH) (n = 8, Acclimation group) or 24 degrees C and 32% RH (n = 4, Control group). Attainment of HA was confirmed by a significant decrease (P = 0.025) of the esophageal temperature (T(es)) threshold for the onset of E(SW) and a significantly elevated E(SW) (P < or = 0.040) during the post-HA exercise tests. HA also gave a significant decrease in resting T(es) (P = 0.006) and a significant increase in plasma volume (P = 0.005). Ventilatory adaptations during exercise tests following HA included significantly decreased T(es) thresholds (P < or = 0.005) for the onset of increases in the ventilatory equivalents for O(2) (VE/VO(2)) and CO(2) (VE/VCO(2)) and a significantly increased VE (P < or = 0.017) at all levels of T(es). Elevated VE was a function of a significantly greater tidal volume (P = 0.003) at lower T(es) and of breathing frequency (P < or = 0.005) at higher T(es). Following HA, the ventilatory threshold was uninfluenced and the relationships between VO(2) and either VE/VO(2) or VE/VCO(2) did not explain the resulting hyperventilation. In conclusion, the results support that exercise VE following passive HA responds similarly to E(SW), and the mechanism accounting for this adaptation is independent of changes of the ventilatory threshold or relationships between VO(2) with each of VE/VO(2) and VE/VCO(2).

Ventilatory oscillations at exercise: effects of hyperoxia, hypercapnia, and acetazolamide.

PubMed

Hermand, Eric; Lhuissier, François J; Larribaut, Julie; Pichon, Aurélien; Richalet, Jean-Paul

2015-06-01

Periodic breathing has been found in patients with heart failure and sleep apneas, and in healthy subjects in hypoxia, during sleep and wakefulness, at rest and, recently, at exercise. To unravel the cardiorespiratory parameters liable to modulate the amplitude and period of ventilatory oscillations, 26 healthy subjects were tested under physiological (exercise) and environmental (hypoxia, hyperoxia, hyperoxic hypercapnia) stresses, and under acetazolamide (ACZ) treatment. A fast Fourier transform spectral analysis of breath-by-breath ventilation (V˙E) evidenced an increase in V˙E peak power under hypercapnia (vs. normoxia and hyperoxia, P < 0.001) and a decrease under ACZ (vs. placebo, P < 0.001), whereas it was not modified in hyperoxia. V˙E period was shortened by exercise in all conditions (vs. rest, P < 0.01) and by hypercapnia (vs. normoxia, P < 0.05) but remained unchanged under ACZ (vs. placebo). V˙E peak power was positively related to cardiac output (Q˙c) and V˙E in hyperoxia (P < 0.01), in hypercapnia (P < 0.001) and under ACZ (P < 0.001). V˙E period was negatively related to Q˙c and V˙E in hyperoxia (P < 0.01 and P < 0.001, respectively), in hypercapnia (P < 0.05 and P < 0.01, respectively) and under ACZ (P < 0.05 and P < 0.01, respectively). Total respiratory cycle time was the main factor responsible for changes in V˙E period. In conclusion, exercise, hypoxia, and hypercapnia increase ventilatory oscillations by increasing Q˙c and V˙E, whereas ACZ decreases ventilatory instability in part by a contrasting action on O2 and CO2 sensing. An intrinsic oscillator might modulate ventilation through a complex system where peripheral chemoreflex would play a key role. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Effects of intracerebroventricular administered fluoxetine on cardio-ventilatory functions in rainbow trout (Oncorhynchus mykiss).

PubMed

Kermorgant, Marc; Lancien, Frédéric; Mimassi, Nagi; Tyler, Charles R; Le Mével, Jean-Claude

2014-09-01

Fluoxetine (FLX) is a selective serotonin (5-HT) reuptake inhibitor present in the aquatic environment which is known to bioconcentrate in the brains of exposed fish. FLX acts as a disruptor of various neuroendocrine functions in the brain, but nothing is known about the possible consequence of FLX exposure on the cardio-ventilatory system in fish. Here we undertook to investigate the central actions of FLX on ventilatory and cardiovascular function in unanesthetized rainbow trout (Oncorhynchus mykiss). Intracerebroventricular (ICV) injection of FLX (dosed between 5 and 25 μg) resulted in a significantly elevated total ventilation (VTOT), with a maximum hyperventilation of +176% (at a dose of 25μg) compared with vehicle injected controls. This increase was due to an increase in ventilatory amplitude (VAMP: +126%) with minor effects on ventilatory frequency. The highest dose of FLX (25 μg) produced a significant increase in mean dorsal aortic blood pressure (PDA: +20%) without effects on heart rate (ƒH). In comparison, intra-arterial injections of FLX (500-2,500 μg) had no effect on ventilation but the highest doses increased both PDA and ƒH. The ICV and IA cardio-ventilatory effects of FLX were very similar to those previously observed following injections of 5-HT, indicating that FLX probably acts via stimulating endogenous 5-HT activity through inhibition of 5-HT transporter(s). Our results demonstrate for the first time in fish that FLX administered within the brain exerts potent stimulatory effects on ventilation and blood pressure increase. The doses of FLX given to fish in our study are higher than the brain concentrations of FLX in fish that result from acute exposure to FLX through the water. Nonetheless, our results indicate possible disrupting action of long term exposure to FLX discharged into the environment on central target sites sensitive to 5-HT involved in cardio-ventilatory control. Copyright © 2013 Elsevier Inc. All rights reserved.

Cerebrovascular and ventilatory responses to acute normobaric hypoxia in girls and women.

PubMed

Morris, Laura E; Flück, Daniela; Ainslie, Philip N; McManus, Ali M

2017-08-01

Physiological responses to hypoxia in children are incompletely understood. We aimed to characterize cerebrovascular and ventilatory responses to normobaric hypoxia in girls and women. Ten healthy girls (9.9 ± 1.7 years; mean ± SD; Tanner stage 1 and 2) and their mothers (43.9 ± 3.5 years) participated. Internal carotid (ICA) and vertebral artery (VA) velocity, diameter and flow (Duplex ultrasound) was recorded pre- and post-1 h of hypoxic exposure (FIO 2  = 0.126;~4000 m) in a normobaric chamber. Ventilation (V˙E) and respiratory drive ( V T / T I ) expressed as delta change from baseline (∆%), and end-tidal carbon-dioxide (P ET CO 2 ) were collected at baseline (BL) and 5, 30 and 60 min of hypoxia (5/30/60 HYP). Heart rate (HR) and oxygen saturation (SpO 2 ) were also collected at these time-points. SpO 2 declined similarly in girls (BL-97%; 60HYP-80%, P  <   0.05) and women (BL-97%; 60HYP-83%, P  <   0.05). Global cerebral blood flow (gCBF) increased in both girls (BL-687; 60HYP-912 mL·min -1 , P  <   0.05) and women (BL-472; 60HYP-651 mL·min -1 , P  <   0.01), though the ratio of ICA:VA (%) contribution to gCBF differed significantly (girls, 75:25%; women, 61:39%). The relative increase in V˙E peaked at 30HYP in both girls (27%, P  <   0.05) and women (19%, P  <   0.05), as did ∆% V T / T I (girls, 41%; women, 27%, P 's < 0.05). Tidal volume ( V T ) increased in both girls and women at 5HYP, remaining elevated above baseline in girls at 30 and 60 HYP, but declined back toward baseline in women. Girls elicit similar increases in gCBF and ventilatory parameters in response to acute hypoxia as women, though the pattern and contributions mediating these responses appear developmentally divergent. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Annual Progress Report, FY 1980, 1 October 1979 - 30 September 1980,

DTIC Science & Technology

1980-10-01

coordinating an integrated pest management program, and constructing initial pilot prototypes, test models, and pro- ducing limited quantities of medical...Screening Test Based on the Ventilatory Responses of Fish . . . . . . . a & a . . . . 25 Chemistry and Molecular Biology of the Disinfection Process...Sink Unit, Surgical, Field (NSN 6545-00-935-4056), Engineering Evaluation of . . . . . . . . . . . . . . . . . . 69 Technical Feasibility Testing (TFT

Intermittent hypoxia, respiratory plasticity and sleep apnea in humans: present knowledge and future investigations.

PubMed

Mateika, Jason H; Syed, Ziauddin

2013-09-15

This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea. Published by Elsevier B.V.

Ventilatory inhomogeneity determined from multiple-breath washouts during sustained microgravity on Spacelab SLS-1.

PubMed

Prisk, G K; Guy, H J; Elliott, A R; Paiva, M; West, J B

1995-02-01

We used multiple-breath N2 washouts (MBNW) to study the inhomogeneity of ventilation in four normal humans (mean age 42.5 yr) before, during, and after 9 days of exposure to microgravity on Spacelab Life Sciences-1. Subjects performed 20-breath MBNW at tidal volumes of approximately 700 ml and 12-breath MBNW at tidal volumes of approximately 1,250 ml. Six indexes of ventilatory inhomogeneity were derived from data from 1) distribution of specific ventilation (SV) from mixed-expired and 2) end-tidal N2, 3) change of slope of N2 washout (semilog plot) with time, 4) change of slope of normalized phase III of successive breaths, 5) anatomic dead space, and 6) Bohr dead space. Significant ventilatory inhomogeneity was seen in the standing position at normal gravity (1 G). When we compared standing 1 G with microgravity, the distributions of SV became slightly narrower, but the difference was not significant. Also, there were no significant changes in the change of slope of the N2 washout, change of normalized phase III slopes, or the anatomic and Bohr dead spaces. By contrast, transition from the standing to supine position in 1 G resulted in significantly broader distributions of SV (P < 0.05) and significantly greater changes in the changes in slope of the N2 washouts (P < 0.001), indicating more ventilatory inhomogeneity in that posture. Thus these techniques can detect relatively small changes in ventilatory inhomogeneity. We conclude that the primary determinants of ventilatory inhomogeneity during tidal breathing in the upright posture are not gravitational in origin.

Functional significance and control of release of pulmonary surfactant in the lizard lung.

PubMed

Wood, P G; Daniels, C B; Orgeig, S

1995-10-01

The amount of pulmonary surfactant in the lungs of the bearded dragon (Pogona vitticeps) increases with increasing body temperature. This increase coincides with a decrease in lung compliance. The relationship between surfactant and lung compliance and the principal stimuli for surfactant release and composition (temperature, ventilatory pattern, and autonomic neurotransmitters) were investigated. We chose to investigate ventilatory pattern (which causes mechanical deformation of the type II cells) and adrenergic agents, because they are the major stimuli for surfactant release in mammals. To examine the effects of body temperature and ventilatory pattern, isolated lungs were ventilated at either 18 or 37 degrees C at different ventilatory regimens. An isolated perfused lung preparation at 27 degrees C was used to analyze the effects of autonomic neurotransmitters. Ventilatory pattern did not affect surfactant release, composition, or lung compliance at either 18 or 37 degrees C. An increase in temperature increased phospholipid reuptake and disproportionately increased cholesterol degradation/uptake. Epinephrine and acetylcholine stimulated phospholipid but not cholesterol release. Removal of surfactant caused a decrease in compliance, regardless of the experimental temperature. Temperature appears to be the principal determinant of lung compliance in the bearded dragon, acting directly to increase the tone of the smooth muscle. Increasing the ambient temperature may result in greater surfactant turnover by increasing cholesterol reuptake/degradation directly and by increasing circulating epinephrine, thereby indirectly increasing phospholipid secretion. We suggest that changing ventilatory pattern may be inadequate as a mechanism for maintaining surfactant homeostasis, given the discontinuous, highly variable reptilian breathing pattern.

Chest tube drainage of transudative pleural effusions hastens liberation from mechanical ventilation.

PubMed

Kupfer, Yizhak; Seneviratne, Chanaka; Chawla, Kabu; Ramachandran, Kavan; Tessler, Sidney

2011-03-01

Pleural effusions occur frequently in patients requiring mechanical ventilatory support. Treatment of the precipitating cause and resolution of the pleural effusion may take considerable time. We retrospectively studied the effect of chest tube drainage of transudative pleural effusions on the liberation of patients from mechanical ventilatory support. Patients in the medical ICU (MICU) at Maimonides Medical Center between January 1, 2009, and October 31, 2009, requiring mechanical ventilatory support with a transudative pleural effusion, were studied retrospectively. They were divided into two groups: standard care and standard care plus chest tube drainage. Chest tubes were placed under ultrasound guidance by trained intensivists. Duration of mechanical ventilatory support was the primary end point. Secondary end points included measures of oxygenation, amount of fluid drained, and complications associated with the chest tube. A total of 168 patients were studied; 88 were treated with standard care and 80 underwent chest tube drainage. Total duration of mechanical ventilatory support was significantly shorter for patients who had chest tube drainage: 3.8±0.5 days vs 6.5±1.1 days for the standard group (P=.03). No differences in oxygenation were noted between the two groups. The average amount of fluid drained was 1,220 mL. No significant complications were caused by chest tube drainage. Chest tube drainage of transudative pleural effusions resulted in more rapid liberation from mechanical ventilatory support. It is a very safe procedure when performed under ultrasound guidance by experienced personnel. ClinicalTrials.gov; Identifier: NCT0114285; URL: www.clinicaltrials.gov.

Ventilatory inhomogeneity determined from multiple-breath washouts during sustained microgravity on Spacelab SLS-1

NASA Technical Reports Server (NTRS)

Prisk, G. Kim; Guy, Harold J. B.; Elliott, Ann R.; Paiva, Manuel; West, John B.

1995-01-01

We used multiple-breath N2 washouts (MBNW) to study the homogeneity of ventilation in four normal humans (mean age 42.5 yr) before, during, and after 9 days of exposure to microgravity on Spacelab Life Sciences-1. Subjects performed 20-breath MBNW at tidal volumes of approximately 700 ml and 12-breath MBNW at tidal volumes of approximately 1,250 ml. Six indexes of ventilatory inhomogeneity were derived from data from (1) distribution of specific ventilation (SV) from mixed-expired and (2) end-tidal N2, (3) change of slope of N2 washout (semilog plot) with time, (4) change of slope of normalized phase III of successive breaths, (5) anatomic lead dead space, and (6) Bohr dead space. Significant ventilatory inhomogeneity was seen in the standing position at normal gravity (1 G). When we compared standing 1 G with microgravity, the distributions of SV became slightly narrower, but the difference was not significant. Also, there were no significant changes in the change of slope of the N2 washout, change of normalized phase III slopes, or the anatomic and Bohr dead spaces. By contrast, transition from the standing to supine position in 1 G resulted in significantly broader distributions of SV and significantly greater changes in the changes in slope of the N2 washouts, indicating more ventilatory inhomogeneity in that posture. Thus these techniques can detect relatively small changes in ventilatory inhomogeneity. We conclude that the primary determinants of ventilatory inhomogeneity during tidal breathing in the upright posture are not gravitational in origin.

Mechano- and metabosensitive alterations after injection of botulinum toxin into gastrocnemius muscle.

PubMed

Caron, Guillaume; Rouzi, Talifujiang; Grelot, Laurent; Magalon, Guy; Marqueste, Tanguy; Decherchi, Patrick

2014-07-01

This study was designed to investigate effects of motor denervation by Clostridium botulinum toxin serotype A (BoNT/A) on the afferent activity of fibers originating from the gastrocnemius muscle of rats. Animals were randomized in two groups, 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle. Locomotor activity was evaluated once per day during 12 days with a test based on footprint measurements of walking rats (sciatic functional index). At the end of the functional assessment period, electrophysiological tests were used to measure muscle properties, metabosensitive afferent fiber responses to chemical (KCl and lactic acid) injections, electrically induced fatigue (EIF), and mechanosensitive responses to tendon vibrations. Additionally, ventilatory response was recorded during repetitive muscle contractions. Then, rats were sacrificed, and the BoNT/A-injected muscles were weighed. Twelve days postinjection we observed a complete motor denervation associated with a significant muscle atrophy and loss of force to direct muscle stimulation. In the BoNT/A group, the metabosensitive responses to KCl injections were unaltered. However, we observed alterations in responses to EIF and to 1 mM of lactic acid (which induces the greatest activation). The ventilatory adjustments during repetitive muscle activation were abolished, and the mechanosensitive fiber responses to tendon vibrations were reduced. These results indicate that BoNT/A alters the sensorimotor loop and may induce insufficient motor and physiological adjustments in patients in whom a motor denervation with BoNT/A was performed. Copyright © 2014 Wiley Periodicals, Inc.

Sensorimotor control of breathing in the mdx mouse model of Duchenne muscular dystrophy.

PubMed

Burns, David P; Roy, Arijit; Lucking, Eric F; McDonald, Fiona B; Gray, Sam; Wilson, Richard J; Edge, Deirdre; O'Halloran, Ken D

2017-11-01

Respiratory failure is a leading cause of mortality in Duchenne muscular dystrophy (DMD), but little is known about the control of breathing in DMD and animal models. We show that young (8 weeks of age) mdx mice hypoventilate during basal breathing due to reduced tidal volume. Basal CO 2 production is equivalent in wild-type and mdx mice. We show that carotid bodies from mdx mice have blunted responses to hyperoxia, revealing hypoactivity in normoxia. However, carotid body, ventilatory and metabolic responses to hypoxia are equivalent in wild-type and mdx mice. Our study revealed profound muscle weakness and muscle fibre remodelling in young mdx diaphragm, suggesting severe mechanical disadvantage in mdx mice at an early age. Our novel finding of potentiated neural motor drive to breathe in mdx mice during maximal chemoactivation suggests compensatory neuroplasticity enhancing respiratory motor output to the diaphragm and probably other accessory muscles. Patients with Duchenne muscular dystrophy (DMD) hypoventilate with consequential arterial blood gas derangement relevant to disease progression. Whereas deficits in DMD diaphragm are recognized, there is a paucity of knowledge in respect of the neural control of breathing in dystrophinopathies. We sought to perform an analysis of respiratory control in a model of DMD, the mdx mouse. In 8-week-old male wild-type and mdx mice, ventilation and metabolism, carotid body afferent activity, diaphragm muscle force-generating capacity, and muscle fibre size, distribution and centronucleation were determined. Diaphragm EMG activity and responsiveness to chemostimulation was determined. During normoxia, mdx mice hypoventilated, owing to a reduction in tidal volume. Basal CO 2 production was not different between wild-type and mdx mice. Carotid sinus nerve responses to hyperoxia were blunted in mdx, suggesting hypoactivity. However, carotid body, ventilatory and metabolic responses to hypoxia were equivalent in wild-type and mdx mice. Diaphragm force was severely depressed in mdx mice, with evidence of fibre remodelling and damage. Diaphragm EMG responses to chemoactivation were enhanced in mdx mice. We conclude that there is evidence of chronic hypoventilation in young mdx mice. Diaphragm dysfunction confers mechanical deficiency in mdx resulting in impaired capacity to generate normal tidal volume at rest and decreased absolute ventilation during chemoactivation. Enhanced mdx diaphragm EMG responsiveness suggests compensatory neuroplasticity facilitating respiratory motor output, which may extend to accessory muscles of breathing. Our results may have relevance to emerging treatments for human DMD aiming to preserve ventilatory capacity. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Habituation of the metabolic and ventilatory responses to cold-water immersion in humans.

PubMed

Tipton, Michael J; Wakabayashi, Hitoshi; Barwood, Martin J; Eglin, Clare M; Mekjavic, Igor B; Taylor, Nigel A S

2013-01-01

An experiment was undertaken to answer long-standing questions concerning the nature of metabolic habituation in repeatedly cooled humans. It was hypothesised that repeated skin and deep-body cooling would produce such a habituation that would be specific to the magnitude of the cooling experienced, and that skin cooling alone would dampen the cold-shock but not the metabolic response to cold-water immersion. Twenty-one male participants were divided into three groups, each of which completed two experimental immersions in 12°C water, lasting until either rectal temperature fell to 35°C or 90min had elapsed. Between these two immersions, the control group avoided cold exposures, whilst two experimental groups completed five additional immersions (12°C). One experimental group repeatedly immersed for 45min in average, resulting in deep-body (1.18°C) and skin temperature reductions. The immersions in the second experimental group were designed to result only in skin temperature reductions, and lasted only 5min. Only the deep-body cooling group displayed a significantly blunted metabolic response during the second experimental immersion until rectal temperature decreased by 1.18°C, but no habituation was observed when they were cooled further. The skin cooling group showed a significant habituation in the ventilatory response during the initial 5min of the second experimental immersion, but no alteration in the metabolic response. It is concluded that repeated falls of skin and deep-body temperature can habituate the metabolic response, which shows tissue temperature specificity. However, skin temperature cooling only will lower the cold-shock response, but appears not to elicit an alteration in the metabolic response. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ventilatory Function in Relation to Mining Experience and Smoking in a Random Sample of Miners and Non-miners in a Witwatersrand Town1

PubMed Central

Sluis-Cremer, G. K.; Walters, L. G.; Sichel, H. S.

1967-01-01

The ventilatory capacity of a random sample of men over the age of 35 years in the town of Carletonville was estimated by the forced expiratory volume and the peak expiratory flow rate. Five hundred and sixty-two persons were working or had worked in gold-mines and 265 had never worked in gold-mines. No difference in ventilatory function was found between the miners and non-miners other than that due to the excess of chronic bronchitis in miners. PMID:6017134

Acidosis slows electrical conduction through the atrio-ventricular node

PubMed Central

Nisbet, Ashley M.; Burton, Francis L.; Walker, Nicola L.; Craig, Margaret A.; Cheng, Hongwei; Hancox, Jules C.; Orchard, Clive H.; Smith, Godfrey L.

2014-01-01

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis. PMID:25009505

Acidosis slows electrical conduction through the atrio-ventricular node.

PubMed

Nisbet, Ashley M; Burton, Francis L; Walker, Nicola L; Craig, Margaret A; Cheng, Hongwei; Hancox, Jules C; Orchard, Clive H; Smith, Godfrey L

2014-01-01

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis.

The effect of endurance training on the ventilatory response to exercise in elite cyclists.

PubMed

Hoogeveen, A R

2000-05-01

The purpose of this study was to investigate the effects of endurance training on the ventilatory response to acute incremental exercise in elite cyclists. Fifteen male elite cyclists [mean (SD) age 24.3 (3.3) years, height 179 (6) cm, body mass 71.1 (7.6) kg, maximal oxygen consumption (VO2max) 69 (7) ml x min(-1) x kg(-1)] underwent two exercise tests on a cycle ergometer. The first test was assessed in December, 6 weeks before the beginning of the cycling season. The second test was performed in June, in the middle of the season. During this period the subjects were expected to be in a highly endurance-trained state. The ventilatory response was assessed during an incremental exercise test (20 W x min(-1)). Oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE), and heart rate (HR) were assessed at the following points during the test: at workloads of 200 W, 250 W, 300 W, 350 W, 400 W and at the subject's maximal workload, at a respiratory exchange ratio (R) of 1, and at the ventilatory threshold (Th(vent)) determined using the V-slope-method. Post-training, the mean (SD) VO2max was increased from the pre-training level of 69 (7) ml x min(-1) x kg(-1) (range 61.4-78.6) to 78 (6) ml x min(-1) x kg(-1) (range 70.5-86.3). The mean post-training VO2 was significantly higher than the pre training value (P < 0.01) at all work rates, at Th(vent) and at R = 1. VO2 was also higher at all work rates except for 200 W and 250 W. VE was significantly higher at Th(vent) and R = 1. Training had no effect on HR at all workloads examined. An explanation for the higher VO2 cost for the same work rate may be that in the endurance-trained state, the adaptation to an exercise stimulus with higher intensity is faster than for the less-trained state. Another explanation may be that at the same work rate, in the less-endurance-trained state power is generated using a significantly higher anaerobic input. The results of this study suggest the following practical recommendations for training management in elite cyclists: (1) the VO2 for a subject at the same work rate may be an indicator of the endurance-trained state (i.e., the higher the VO2, the higher the endurance-trained capacity), and (2) the need for multiple exercise tests for determining the HR at Th(vent) during a cycling season is doubtful since at Th(vent) this parameter does not differ much following endurance training.

Resolution of exercise oscillatory ventilation with adaptive servoventilation in patients with chronic heart failure and Cheyne-Stokes respiration: preliminary study.

PubMed

Kazimierczak, Anna; Krzyżanowski, Krystian; Wierzbowski, Robert; Ryczek, Robert; Smurzyński, Paweł; Michałkiewicz, Dariusz; Orski, Zbigniew; Gielerak, Grzegorz

2011-01-01

Exercise oscillatory ventilation (EOV) is a common pattern of breathing in heart failure (HF) patients, and indicates a poor prognosis. To investigate the effects of adaptive servoventilation (ASV) on ventilatory response during exercise. We studied 39 HF patients with left ventricular ejection fraction (LVEF) £ 45. Cardiorespiratory polygraphy, cardiopulmonary exercise testing (CPET), echocardiography, and measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration were performed. Twenty patients with Cheyne-Stokes respiration and apnoea-hypopnoea index (AHI) ≥ 15/h were identified. Of these, 11 patients were successfully titrated on ASV and continued therapy. In the third month of ASV treatment, polygraphy, CPET, echocardiography, and measurement of NT-proBNP concentration were performed again. The EOV was detected at baseline in 12 (31%) HF patients, including eight (67%) who underwent ASV. The EOV was associated with significantly lower LVEF, peak oxygen uptake (VO(2)), and ventilatory anaerobic threshold (VAT), and a significantly higher left ventricular diastolic diameter (LVDD), slope of ventilatory equivalent for carbon dioxide (VE/VCO(2)), AHI, central AHI and NT-proBNP concentration. In seven patients with EOV, reversal of EOV in the third month of ASV therapy was observed; only in one patient did EOV persist (p = 0.0156). The EOV can be reversed with ASV therapy. The EOV in association with central sleep apnoea and Cheyne- -Stokes respiration (CSA/CSR) is prevalent in HF patients and correlates with severity of the disease.

New perspectives concerning feedback influences on cardiorespiratory control during rhythmic exercise and on exercise performance.

PubMed

Dempsey, Jerome A

2012-09-01

The cardioaccelerator and ventilatory responses to rhythmic exercise in the human are commonly viewed as being mediated predominantly via feedforward 'central command' mechanisms, with contributions from locomotor muscle afferents to the sympathetically mediated pressor response. We have assessed the relative contributions of three types of feedback afferents on the cardiorespiratory response to voluntary, rhythmic exercise by inhibiting their normal 'tonic' activity in healthy animals and humans and in chronic heart failure. Transient inhibition of the carotid chemoreceptors during moderate intensity exercise reduced muscle sympathetic nerve activity (MSNA) and increased limb vascular conductance and blood flow; and reducing the normal level of respiratory muscle work during heavier intensity exercise increased limb vascular conductance and blood flow. These cardiorespiratory effects were prevented via ganglionic blockade and were enhanced in chronic heart failure and in hypoxia. Blockade of μ opioid sensitive locomotor muscle afferents, with preservation of central motor output via intrathecal fentanyl: (a) reduced the mean arterial blood pressure (MAP), heart rate and ventilatory responses to all steady state exercise intensities; and (b) during sustained high intensity exercise, reduced O(2) transport, increased central motor output and end-exercise muscle fatigue and reduced endurance performance. We propose that these three afferent reflexes - probably acting in concert with feedforward central command - contribute significantly to preserving O(2) transport to locomotor and to respiratory muscles during exercise. Locomotor muscle afferents also appear to provide feedback concerning the metabolic state of the muscle to influence central motor output, thereby limiting peripheral fatigue development.

Cardiopulmonary Responses to Supine Cycling during Short-Arm Centrifugation

NASA Technical Reports Server (NTRS)

Vener, J. M.; Simonson, S. R.; Stocks, J.; Evettes, S.; Bailey, K.; Biagini, H.; Jackson, C. G. R.; Greenleaf, J. E.; Dalton, Bonnie P. (Technical Monitor)

2001-01-01

The purpose of this study was to investigate cardiopulmonary responses to supine cycling with concomitant +G(sub z) acceleration using the NASA/Ames Human Powered Short-Arm Centrifuge (HPC). Subjects were eight consenting males (32+/-5 yrs, 178+/-5 cm, 86.1+/- 6.2 kg). All subjects completed two maximal exercise tests on the HPC (with and without acceleration) within a three-day period. A two tailed t-test with statistical significance set at p less than or equal to 0.05 was used to compare treatments. Peak acceleration was 3.4+/-0.1 G(sub z), (head to foot acceleration). Peak oxygen uptake (VO2(sub peak) was not different between treatment groups (3.1+/-0.1 Lmin(exp -1) vs. 3.2+/-0.1 Lmin(exp -1) for stationary and acceleration trials, respectively). Peak HR and pulmonary minute ventilation (V(sub E(sub BTPS))) were significantly elevated (p less than or equal to 0.05) for the acceleration trial (182+/-3 BPM (Beats per Minute); 132.0+/-9.0 Lmin(exp -1)) when compared to the stationary trial (175+/-3 BPM; 115.5+/-8.5 Lmin(exp -1)). Ventilatory threshold expressed as a percent of VO2(sub peak) was not different for acceleration and stationary trials (72+/-2% vs. 68+/-2% respectively). Results suggest that 3.4 G(sub z) acceleration does not alter VO2(sub peak) response to supine cycling. However, peak HR and V(sub E(sub BTPS)) response may be increased while ventilatory threshold response expressed as a function of percent VO2(sub peak) is relatively unaffected. Thus, traditional exercise prescription based on VO2 response would be appropriate for this mode of exercise. Prescriptions based on HR response may require modification.

Antenatal substance misuse and smoking and newborn hypoxic challenge response.

PubMed

Ali, Kamal; Rossor, Thomas; Bhat, Ravindra; Wolff, Kim; Hannam, Simon; Rafferty, Gerrard F; Peacock, Janet L; Greenough, Anne

2016-03-01

Infants of smoking (S) and substance misusing (SM) mothers have an increased risk of sudden infant death syndrome. The aim of this study was to test the hypothesis that infants of SM or S mothers compared with infants of non-SM, non-smoking mothers (controls) would have a poorer ventilatory response to hypoxia, which was particularly marked in the SM infants. Physiological study. Tertiary perinatal centre. 21 SM; 21 S and 19 control infants. Infants were assessed before maternity/neonatal unit discharge. Maternal and infant urine samples were tested for cotinine, cannabinoids, opiates, amphetamines, methadone, cocaine and benzodiazepines. During quiet sleep, the infants were switched from breathing room air to 15% oxygen and changes in minute volume were assessed. The SM infants had a greater mean increase (p=0.028, p=0.034, respectively) and a greater magnitude of decline (p<0.001, p=0.018, respectively) in minute volume than the S infants and the controls. The rate of decline in minute volume was greater in the SM infants (p=0.008) and the S infants (p=0.011) compared with the controls. Antenatal substance misuse and smoking affect the infant's ventilatory response to a hypoxic challenge. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease.

PubMed

Wallen, M P; Hall, A; Dias, K A; Ramos, J S; Keating, S E; Woodward, A J; Skinner, T L; Macdonald, G A; Arena, R; Coombes, J S

2017-10-01

Patients with advanced liver disease may develop portal hypertension that can result in variceal haemorrhage. Beta-blockers reduce portal pressure and minimise haemorrhage risk. These medications may attenuate measures of cardiopulmonary performance, such as the ventilatory threshold and peak oxygen uptake measured via cardiopulmonary exercise testing. To determine the effect of beta-blockers on cardiopulmonary exercise testing variables in patients with advanced liver disease. This was a cross-sectional analysis of 72 participants who completed a cardiopulmonary exercise test before liver transplantation. All participants remained on their usual beta-blocker dose and timing prior to the test. Variables measured during cardiopulmonary exercise testing included the ventilatory threshold, peak oxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and the ventilatory equivalents for carbon dioxide slope. Participants taking beta-blockers (n = 28) had a lower ventilatory threshold (P <.01) and peak oxygen uptake (P = .02), compared to participants not taking beta-blockers. After adjusting for age, the model of end-stage liver-disease score, liver-disease aetiology, presence of refractory ascites and ventilatory threshold remained significantly lower in the beta-blocker group (P = .04). The oxygen uptake efficiency slope was not impacted by beta-blocker use. Ventilatory threshold is reduced in patients with advanced liver disease taking beta-blockers compared to those not taking the medication. This may incorrectly risk stratify patients on beta-blockers and has implications for patient management before and after liver transplantation. The oxygen uptake efficiency slope was not influenced by beta-blockers and may therefore be a better measure of cardiopulmonary performance in this patient population. © 2017 John Wiley & Sons Ltd.

Increased ventilatory variability and complexity in patients with hyperventilation disorder.

PubMed

Bokov, Plamen; Fiamma, Marie-Noëlle; Chevalier-Bidaud, Brigitte; Chenivesse, Cécile; Straus, Christian; Similowski, Thomas; Delclaux, Christophe

2016-05-15

It has been hypothesized that hyperventilation disorders could be characterized by an abnormal ventilatory control leading to enhanced variability of resting ventilation. The variability of tidal volume (VT) often depicts a nonnormal distribution that can be described by the negative slope characterizing augmented breaths formed by the relationship between the probability density distribution of VT and VT on a log-log scale. The objectives of this study were to describe the variability of resting ventilation [coefficient of variation (CV) of VT and slope], the stability in respiratory control (loop, controller and plant gains characterizing ventilatory-chemoresponsiveness interactions) and the chaotic-like dynamics (embedding dimension, Kappa values characterizing complexity) of resting ventilation in patients with a well-defined dysfunctional breathing pattern characterized by air hunger and constantly decreased PaCO2 during a cardiopulmonary exercise test. Compared with 14 healthy subjects with similar anthropometrics, 23 patients with hyperventilation were characterized by increased variability of resting tidal ventilation (CV of VT median [interquartile]: 26% [19-35] vs. 36% [28-48], P = 0.020; slope: -6.63 [-7.65; -5.36] vs. -3.88 [-5.91; -2.66], P = 0.004) that was not related to increased chemical drive (loop gain: 0.051 [0.039-0.221] vs. 0.044 [0.012-0.087], P = 0.149) but that was related to an increased ventilatory complexity (Kappa values, P < 0.05). Plant gain was decreased in patients and correlated with complexity (with Kappa 5 - degree 5: Rho = -0.48, P = 0.006). In conclusion, well-defined patients suffering from hyperventilation disorder are characterized by increased variability of their resting ventilation due to increased ventilatory complexity with stable ventilatory-chemoresponsiveness interactions. Copyright © 2016 the American Physiological Society.

Participation of the dorsal periaqueductal grey matter in the hypoxic ventilatory response in unanaesthetized rats.

PubMed

Lopes, L T; Biancardi, V; Vieira, E B; Leite-Panissi, C; Bícego, K C; Gargaglioni, L H

2014-07-01

Although periaqueductal grey matter activation is known to elicit respiratory and cardiovascular responses, the role of this midbrain area in the compensatory responses to hypoxia is still unknown. To test the participation of the periaqueductal grey matter in cardiorespiratory and thermal responses to hypoxia in adult male Wistar rats, we performed a chemical lesion of the dorsolateral/dorsomedial or the ventrolateral/lateral periaqueductal grey matter using ibotenic acid. Pulmonary ventilation, mean arterial pressure, heart rate and body temperature were measured in unanaesthetized rats during normoxic and hypoxic exposure (5, 15, 30 min, 7% O2). An ibotenic acid lesion of the dorsolateral/dorsomedial periaqueductal grey matter caused a higher increase in pulmonary ventilation (67.1%, 1730±282.5 mL kg(-1) min(-1)) compared to the Sham group (991.4±194 mL kg(-1) min(-1)) after 15 min in hypoxia, whereas for the ventrolateral/Lateral periaqueductal grey matter lesion, no differences were observed between groups. Mean arterial pressure, heart rate and body temperature were not affected by a dorsolateral/dorsomedial or ventrolateral/lateral periaqueductal grey matter lesion. Middle to caudal portions of the dorsolateral/dorsomedial periaqueductal grey matter neurones modulate the hypoxic ventilatory response, exerting an inhibitory modulation during low O2 situations. In addition, the middle to caudal portions of the dorsolateral/dorsomedial or ventrolateral/lateral periaqueductal grey matter do not appear to exert a tonic role on cardiovascular or thermal parameters during normoxic and hypoxic conditions. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Cost containment and mechanical ventilation in the United States.

PubMed

Cohen, I L; Booth, F V

1994-08-01

In many ICUs, admission and discharge hinge on the need for intubation and ventilatory support. As few as 5% to 10% of ICU patients require prolonged mechanical ventilation, and this patient group consumes > or = 50% of ICU patient days and ICU resources. Prolonged ventilatory support and chronic ventilator dependency, both in the ICU and non-ICU settings, have a significant and growing impact on healthcare economics. In the United States, the need for prolonged mechanical ventilation is increasingly recognized as separate and distinct from the initial diagnosis and/or procedure that leads to hospitalization. This distinction has led to improved reimbursement under the prospective diagnosis-related group (DRG) system, and demands more precise accounting from healthcare providers responsible for these patients. Using both published and theoretical examples, mechanical ventilation in the United States is discussed, with a focus on cost containment. Included in the discussion are ventilator teams, standards of care, management protocols, stepdown units, rehabilitation units, and home care. The expanding role of total quality management (TQM) is also presented.

[Diaphragm pacing for the ventilatory support of the quadriplegic patients with respiratory paralysis].

PubMed

Cheng, H; Wang, L S; Pan, H C; Shoung, H M; Lee, L S

1992-02-01

Electrical stimulation of the phrenic nerve to pace the diaphragm in patients with chronic ventilatory insufficiency has been an established therapeutic modality since William W.L. Glenn first described using radiofrequency signals in 1978 to stimulate the phrenic nerves. Before this event, patients who were ventilator-dependent and thus bedridden because of respiratory paralysis associated with quadriplegia usually anticipated little chance for physical or psychosocial rehabilitation. Two cases of C1-C2 subluxtion with cord injury and chronic ventilatory insufficiency were implanted at VGH-Taipei with diaphragm pacemaker in 1988. Postoperative phrenic nerve stimulation was given according to individual training schedule. One case with total phrenic paralysis received bilateral phrenic nerve stimulation and became weaned from the ventilator 6 months later. The other case with partially active ventilatory function received unilateral phrenic nerve stimulation to compensate the ventilation. However, its final outcome still showed the necessity of a bilateral mode to achieve adequate ventilation irrespective of strenuous training for 2 years.

Effects of Hypoxia and Hypercapnic Hypoxia on Oxygen Transport and Acid-Base Status in the Atlantic Blue Crab, Callinectes sapidus, During Exercise.

PubMed

Lehtonen, Mark P; Burnett, Louis E

2016-11-01

The responses of estuarine invertebrates to hypoxic conditions are well established. However, many studies have investigated hypoxia as an isolated condition despite its frequent co-occurrence with hypercapnia (elevated CO 2 ). Although many studies suggest deleterious effects, hypercapnia has been observed to improve blue crab walking performance in hypoxia. To investigate the physiological effects of combined hypercapnic hypoxia, we measured Po 2 , pH, [l-lactate], Pco 2 , and total O 2 in pre- and postbranchial hemolymph sampled from blue crabs during walking exercise. Crabs walked at 8 m min -1 on an aquatic treadmill in normoxic (100% air saturation), moderately hypoxic (50%), and severely hypoxic (20%) seawater with and without the addition of hypercapnia (about 2% CO 2 ). Respiration was almost completely aerobic in normoxic conditions, with little buildup of lactate. During exercise under severe hypoxia, lactate increased from 1.4 to 11.0 mM, indicating a heavy reliance on anaerobic respiration. The O 2 saturation of arterial hemocyanin was 47% in severe hypoxia after 120 min, significantly lower than in normoxia (80%). However, the addition of hypercapnia significantly increased the percentage saturation of arterial hemocyanin in severe hypoxia to 92% after 120 min of exercise, equivalent to normoxic levels. Hypercapnia in severe hypoxia also caused a marked increase in hemolymph Pco 2 (around 1.1 kPa), but caused only a minor decrease in pH of 0.1 units. We suggest that the improved O 2 saturation at the gills results from a specific effect of molecular CO 2 on hemocyanin oxygen binding affinity, which works independently of and counter to the effects of decreased pH. © 2016 Wiley Periodicals, Inc.

A decrease in nasal CO2 stimulates breathing in the tegu lizard.

PubMed

Coates, E L; Furilla, R A; Ballam, G O; Bartlett, D

1991-10-01

Tegu lizards decrease ventilatory frequency (f) when constant CO2, as low as 0.4%, is delivered to the nasal cavities. In contrast, CO2, as high as 6%, pulsed into the nasal cavities during the expiratory phase of the breathing cycle does not alter f. The purpose of the present study was to investigate further the effect of nasal CO2 pattern on f in tegu lizards. Specifically, we tested: (1) whether f was affected by CO2 delivered to the nasal cavities during the inspiratory phase of the breathing cycle, and (2) whether pulsed decreases in nasal CO2 from 4% to 2% and from 4% to 0% would remove the f inhibition caused by constant nasal CO2. Ventilation was measured using a pneumotachograph and pressure transducer in-line with an endotracheal T-tube inserted through the glottis. CO2 was delivered to the nasal cavities through small tubes inserted into the external nares. Ventilatory frequency was not significantly altered when 4% CO2 was pulsed into the nasal cavities during inspiration. Dropping the CO2 in the nasal cavities from 4% to 0% at either 15 cycles/min (0.25 Hz) or for one cycle stimulated breathing. There was no significant difference between the f response to a drop in CO2 from 4% to 0% and that to a drop in CO2 from 4% to 2%. The failure to link the phasic CO2 ventilatory response to a phase in the respiratory cycle indicates that the nasal CO2 receptors do not participate in the breath-by-breath regulation of breathing in these lizards. The observation that small decreases in nasal CO2 abolished the f inhibition caused by constant nasal CO2 provides further evidence for the ability of the nasal CO2 receptors to distinguish between pulsed and constant CO2.

Comparison of the metabolic and ventilatory response to hypoxia and H2S in unsedated mice and rats.

PubMed

Haouzi, Philippe; Bell, Harold J; Notet, Veronique; Bihain, Bernard

2009-07-31

Hypoxia alters the control of breathing and metabolism by increasing ventilation through the arterial chemoreflex, an effect which, in small-sized animals, is offset by a centrally mediated reduction in metabolism and respiration. We tested the hypothesis that hydrogen sulfide (H(2)S) is involved in transducing these effects in mammals. The rationale for this hypothesis is twofold. Firstly, inhalation of a 20-80 ppm H(2)S reduces metabolism in small mammals and this effect is analogous to that of hypoxia. Secondly, endogenous H(2)S appears to mediate some of the cardio-vascular effects of hypoxia in non-mammalian species. We, therefore, compared the ventilatory and metabolic effects of exposure to 60 ppm H(2)S and to 10% O(2) in small and large rodents (20g mice and 700g rats) wherein the metabolic response to hypoxia has been shown to differ according to body mass. H(2)S and hypoxia produced profound depression in metabolic rate in the mice, but not in the large rats. The depression was much faster with H(2)S than with hypoxia. The relative hyperventilation produced by hypoxia in the mice was replaced by a depression with H(2)S, which paralleled the drop in metabolic rate. In the larger rats, ventilation was stimulated in hypoxia, with no change in metabolism, while H(2)S affected neither breathing nor metabolism. When mice were simultaneously exposed to H(2)S and hypoxia, the stimulatory effects of hypoxia on breathing were abolished, and a much larger respiratory and metabolic depression was observed than with H(2)S alone. H(2)S had, therefore, no stimulatory effect on the arterial chemoreflex. The ventilatory depression during hypoxia and H(2)S in small mammals appears to be dependent upon the ability to decrease metabolism.

Coupling of EIT with computational lung modeling for predicting patient-specific ventilatory responses.

PubMed

Roth, Christian J; Becher, Tobias; Frerichs, Inéz; Weiler, Norbert; Wall, Wolfgang A

2017-04-01

Providing optimal personalized mechanical ventilation for patients with acute or chronic respiratory failure is still a challenge within a clinical setting for each case anew. In this article, we integrate electrical impedance tomography (EIT) monitoring into a powerful patient-specific computational lung model to create an approach for personalizing protective ventilatory treatment. The underlying computational lung model is based on a single computed tomography scan and able to predict global airflow quantities, as well as local tissue aeration and strains for any ventilation maneuver. For validation, a novel "virtual EIT" module is added to our computational lung model, allowing to simulate EIT images based on the patient's thorax geometry and the results of our numerically predicted tissue aeration. Clinically measured EIT images are not used to calibrate the computational model. Thus they provide an independent method to validate the computational predictions at high temporal resolution. The performance of this coupling approach has been tested in an example patient with acute respiratory distress syndrome. The method shows good agreement between computationally predicted and clinically measured airflow data and EIT images. These results imply that the proposed framework can be used for numerical prediction of patient-specific responses to certain therapeutic measures before applying them to an actual patient. In the long run, definition of patient-specific optimal ventilation protocols might be assisted by computational modeling. NEW & NOTEWORTHY In this work, we present a patient-specific computational lung model that is able to predict global and local ventilatory quantities for a given patient and any selected ventilation protocol. For the first time, such a predictive lung model is equipped with a virtual electrical impedance tomography module allowing real-time validation of the computed results with the patient measurements. First promising results obtained in an acute respiratory distress syndrome patient show the potential of this approach for personalized computationally guided optimization of mechanical ventilation in future. Copyright © 2017 the American Physiological Society.

Respiration and the generation of rhythmic outputs in insects.

PubMed

Kammer, A E

1976-07-01

In insects gas exchange may be: 1) entirely passive, when metabolic rate is low; 2) enhanced automatically by muscle contractions that produce movements, e.g., wing movements in flight; or 3) produced by ventilatory movements, particularly of the abdomen. In terrestrial insects such as locusts and cockroaches ventilatory movements are governed by a dominant oscillator in the metathoracic or anterior abdominal ganglion. The dominant oscillator overrides local oscillators in the abdominal ganglia and thus sets the rhythm for the entire abdomen, and it also controls spiracle opening and closing in several thoracic and abdominal segments. This ventilatory control mechanism appears to be different from that generating metachronal rhythms such as occur in the ventilatory and locomotory movements of aquatic arthropods. There are now several examples of rhythms, both ventilatory and locomotory, that can be generated by the central nervous system in the absence of phasic sensory feedback, but the mechanism of rhythm production is not known. Studies of ganglionic output suggest that neuronal oscillators can produce a range of frequencies and that some oscillators may be employed in more than one function or behavior. The mechanisms by which central oscillators are coupled to the output motorneurons are also not known; large phase changes suggest that in some cases different coupling interneurons are active. Intracellular recordings from identified neurons have begun to clarify the important roles of interneurons in the production of motor patterns.

Impact of backpack load on ventilatory function among 9-12 year old Saudi girls.

PubMed

Al-Katheri, Abeer E

2013-12-01

To explore the backpack load as a percentile of body weight (BW) and its impact on ventilatory function including tidal volume (Vt), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, peak expiratory flow (PEF), and maximum voluntary ventilation (MVV) among 9-12 year old Saudi girls. This is a prospective, experimental study of 91 Saudi girls aged between 9-12 years from primary schools in Riyadh, Saudi Arabia. The study took place in King Saud University, Riyadh, Saudi Arabia between April 2012 and May 2012. Ventilatory function was measured under 2 conditions: a free standing position without carrying a backpack, and while carrying a backpack. The backpack load observed was 13.8% of the BW, which is greater than the recommended limit (10% BW). All values of ventilatory function were significantly reduced after carrying the backpack (p<0.001) with the exception of FEV1/FVC (p>0.178). The reduction was observed even with the lowest backpack load (7.4% BW). A significant reduction was reported for most of the ventilatory function parameters while carrying the backpack. This reduction was apparent even with the least backpack load (7.4% BW) carried by the participants. This study recommends that the upper safe limit of backpack load carried by Saudi girls aged 9-12 years should be less than 7.4% of BW.

Benefits of Manometer in Non-Invasive Ventilatory Support.

PubMed

Lacerda, Rodrigo Silva; de Lima, Fernando Cesar Anastácio; Bastos, Leonardo Pereira; Fardin Vinco, Anderson; Schneider, Felipe Britto Azevedo; Luduvico Coelho, Yves; Fernandes, Heitor Gomes Costa; Bacalhau, João Marcus Ramos; Bermudes, Igor Matheus Simonelli; da Silva, Claudinei Ferreira; da Silva, Luiza Paterlini; Pezato, Rogério

2017-12-01

Introduction Effective ventilation during cardiopulmonary resuscitation (CPR) is essential to reduce morbidity and mortality rates in cardiac arrest. Hyperventilation during CPR reduces the efficiency of compressions and coronary perfusion. Problem How could ventilation in CPR be optimized? The objective of this study was to evaluate non-invasive ventilator support using different devices. The study compares the regularity and intensity of non-invasive ventilation during simulated, conventional CPR and ventilatory support using three distinct ventilation devices: a standard manual resuscitator, with and without airway pressure manometer, and an automatic transport ventilator. Student's t-test was used to evaluate statistical differences between groups. P values <.05 were regarded as significant. Peak inspiratory pressure during ventilatory support and CPR was significantly increased in the group with manual resuscitator without manometer when compared with the manual resuscitator with manometer support (MS) group or automatic ventilator (AV) group. The study recommends for ventilatory support the use of a manual resuscitator equipped with MS or AVs, due to the risk of reduction in coronary perfusion pressure and iatrogenic thoracic injury during hyperventilation found using manual resuscitator without manometer. Lacerda RS , de Lima FCA , Bastos LP , Vinco AF , Schneider FBA , Coelho YL , Fernandes HGC , Bacalhau JMR , Bermudes IMS , da Silva CF , da Silva LP , Pezato R . Benefits of manometer in non-invasive ventilatory support. Prehosp Disaster Med. 2017;32(6):615-620.

Eszopiclone and Dexmedetomidine Depress Ventilation in Obese Rats with Features of Metabolic Syndrome

PubMed Central

Filbey, William A.; Sanford, David T.; Baghdoyan, Helen A.; Koch, Lauren G.; Britton, Steven L.; Lydic, Ralph

2014-01-01

Study Objectives: Obesity alters the therapeutic window of sedative/hypnotic drugs and increases the probability of respiratory complications. The current experiments used an established rodent model of obesity to test the hypothesis that the sedative/hypnotic drugs eszopiclone and dexmedetomidine alter ventilation differentially in obese rats compared with lean/fit rats. Design: This study used a within-groups/between-groups experimental design. Setting: University of Michigan. Participants: Experiments were conducted using lean/fit rats (n = 21) and obese rats (n = 21) that have features of metabolic syndrome. Interventions: Breathing was measured with whole-body plethysmography after systemic administration of vehicle (control), the nonbenzodiazepine, benzodiazepine site agonist eszopiclone, or the alpha-2 adrenergic receptor agonist dexmedetomidine. Measurements and Results: Data were analyzed using two-way analysis of variance and appropriate post hoc comparisons. At baseline, the obese/metabolic syndrome rats had increased respiratory rates (21.6%), lower tidal volumes/body weight (-24.1%), and no differences in minute ventilation compared to lean/fit rats. In the obese rats, respiratory rate was decreased by dexmedetomidine (-29%), but not eszopiclone. In the lean and the obese rats, eszopiclone decreased tidal volume (-12%). Both sedative/hypnotic drugs caused a greater decrease in minute ventilation in the obese (-26.3%) than lean (-18%) rats. Inspiratory flow rate (VT / TI) of the obese rats was decreased by dexmedetomidine (-10.6%) and eszopiclone (-18%). Duty cycle (TI / TTOT) in both rat lines was decreased by dexmedetomidine (-16.5%) but not by eszopiclone. Conclusions: Dexmedetomidine, in contrast to eszopiclone, decreased minute ventilation in the obese/metabolic syndrome rats by depressing both duty cycle and inspiratory flow rate. The results show for the first time that the obese phenotype differentially modulates the respiratory effects of eszopiclone and dexmedetomidine. These differences in breathing are consistent with previously documented differences in sleep between lean/fit and obese rats. These findings also encourage future studies of obese/metabolic syndrome rats that quantify the effect of sedative/hypnotic drugs on respiratory mechanics as well as hypoxic and hypercapnic ventilatory responses. Continued findings of favorable homology between obese humans and rodents will support the interpretation that these obese rats offer a unique animal model for mechanistic studies. Citation: Filbey WA, Sanford DT, Baghdoyan HA, Koch LG, Britton SL, Lydic R. Eszopiclone and dexmedetomidine depress ventilation in obese rats with features of metabolic syndrome. SLEEP 2014;37(5):871-880. PMID:24790265

Effects of a helium/oxygen mixture on individuals' lung function and metabolic cost during submaximal exercise for participants with obstructive lung diseases.

PubMed

Häussermann, Sabine; Schulze, Anja; Katz, Ira M; Martin, Andrew R; Herpich, Christiane; Hunger, Theresa; Texereau, Joëlle

2015-01-01

Helium/oxygen therapies have been studied as a means to reduce the symptoms of obstructive lung diseases with inconclusive results in clinical trials. To better understand this variability in results, an exploratory physiological study was performed comparing the effects of helium/oxygen mixture (78%/22%) to that of medical air. The gas mixtures were administered to healthy, asthmatic, and chronic obstructive pulmonary disease (COPD) participants, both moderate and severe (6 participants in each disease group, a total of 30); at rest and during submaximal cycling exercise with equivalent work rates. Measurements of ventilatory parameters, forced spirometry, and ergospirometry were obtained. There was no statistical difference in ventilatory and cardiac responses to breathing helium/oxygen during submaximal exercise. For asthmatics, but not for the COPD participants, there was a statistically significant benefit in reduced metabolic cost, determined through measurement of oxygen uptake, for the same exercise work rate. However, the individual data show that there were a mixture of responders and nonresponders to helium/oxygen in all of the groups. The inconsistent response to helium/oxygen between individuals is perhaps the key drawback to the more effective and widespread use of helium/oxygen to increase exercise capacity and for other therapeutic applications.

A field study of the ventilatory response to ambient temperature and pressure in sport diving.

PubMed Central

Muller, F L

1995-01-01

This study reports on the relationship between minute ventilation (VE) and environmental variables of temperature (T) and pressure (P) during open water diving. The author conducted a total of 38 dives involving either a light (20 dives) or a moderate (18 dives) level of physical activity. Within each of these groups, P and T taken together accounted for about two thirds of the variance in the VE data. A very significant increase in VE was observed as T decreased (1 < T(degrees C) < 22), and the magnitude of this increase at a given pressure level was similar in the 'light' and the 'moderate' data sets. A second order observation, particularly notable at lower temperature, was the decrease in VE with increasing pressure under conditions of light work. Empirical functions of the from VE = A+B/P n[1 + exp(T - 8)/10], where A, B, and n are adjustable variables, could accommodate both data sets over the whole range of T and P. These results are the first obtained under actual diving conditions to provide evidence for interactions between P, T, and VE. Understanding the physiological mechanisms by which these interactions occur would assist in appreciation of the limitations imposed on scuba divers by the environmental conditions as they affect their ventilatory responses. PMID:8800853

Proportional mechanical ventilation through PWM driven on/off solenoid valve.

PubMed

Sardellitti, I; Cecchini, S; Silvestri, S; Caldwell, D G

2010-01-01

Proportional strategies for artificial ventilation are the most recent form of synchronized partial ventilatory assistance and intra-breath control techniques available in clinical practice. Currently, the majority of commercial ventilators allowing proportional ventilation uses proportional valves to generate the flow rate pattern. This paper proposes on-off solenoid valves for proportional ventilation given their small size, low cost and short switching time, useful for supplying high frequency ventilation. A new system based on a novel fast switching driver circuit combined with on/off solenoid valve is developed. The average short response time typical of onoff solenoid valves was further reduced through the driving circuit for the implementation of PWM control. Experimental trials were conducted for identifying the dynamic response of the PWM driven on/off valve and for verifying its effectiveness in generating variable-shaped ventilatory flow rate patterns. The system was able to smoothly follow the reference flow rate patterns also changing in time intervals as short as 20 ms, achieving a flow rate resolution up to 1 L/min and repeatability in the order of 0.5 L/min. Preliminary results showed the feasibility of developing a stand alone portable device able to generate both proportional and high frequency ventilation by only using on-off solenoid valves.

In vivo microscopy of the mouse brain using multiphoton laser scanning techniques

NASA Astrophysics Data System (ADS)

Yoder, Elizabeth J.

2002-06-01

The use of multiphoton microscopy for imaging mouse brain in vivo offers several advantages and poses several challenges. This tutorial begins by briefly comparing multiphoton microscopy with other imaging modalities used to visualize the brain and its activity. Next, an overview of the techniques for introducing fluorescence into whole animals to generate contrast for in vivo microscopy using two-photon excitation is presented. Two different schemes of surgically preparing mice for brain imaging with multiphoton microscopy are reviewed. Then, several issues and problems with in vivo microscopy - including motion artifact, respiratory and cardiac rhythms, maintenance of animal health, anesthesia, and the use of fiducial markers - are discussed. Finally, examples of how these techniques have been applied to visualize the cerebral vasculature and its response to hypercapnic stimulation are provided.

[Lung protective ventilation. Ventilatory modes and ventilator parameters].

PubMed

Schädler, Dirk; Weiler, Norbert

2008-06-01

Mechanical ventilation has a considerable potential for injuring the lung tissue. Therefore, attention has to be paid to the proper choice of ventilatory mode and settings to secure lung-protective ventilation whenever possible. Such ventilator strategy should account for low tidal volume ventilation (6 ml/kg PBW), limited plateau pressure (30 to 35 cm H2O) and positive end-expiratory pressure (PEEP). It is unclear whether pressure controlled or volume controlled ventilation with square flow profile is beneficial. The adjustment of inspiration and expiration time should consider the actual breathing mechanics and anticipate the generation of intrinsic PEEP. Ventilatory modes with the possibility of supporting spontaneous breathing should be used as soon as possible.

PDGF-beta receptor expression and ventilatory acclimatization to hypoxia in the rat.

PubMed

Alea, O A; Czapla, M A; Lasky, J A; Simakajornboon, N; Gozal, E; Gozal, D

2000-11-01

Activation of platelet-derived growth factor-beta (PDGF-beta) receptors in the nucleus of the solitary tract (nTS) modulates the late phase of the acute hypoxic ventilatory response (HVR) in the rat. We hypothesized that temporal changes in PDGF-beta receptor expression could underlie the ventilatory acclimatization to hypoxia (VAH). Normoxic ventilation was examined in adult Sprague-Dawley rats chronically exposed to 10% O(2), and at 0, 1, 2, 7, and 14 days, Northern and Western blots of the dorsocaudal brain stem were performed for assessment of PDGF-beta receptor expression. Although no significant changes in PDGF-beta receptor mRNA occurred over time, marked attenuation of PDGF-beta receptor protein became apparent after day 7 of hypoxic exposure. Such changes were significantly correlated with concomitant increases in normoxic ventilation, i.e., with VAH (r: -0.56, P < 0.005). In addition, long-term administration of PDGF-BB in the nTS via osmotic pumps loaded with either PDGF-BB (n = 8) or vehicle (Veh; n = 8) showed that although no significant changes in the magnitude of acute HVR occurred in Veh over time, the typical attenuation of HVR by PDGF-BB decreased over time. Furthermore, PDGF-BB microinjections did not attenuate HVR in acclimatized rats at 7 and 14 days of hypoxia (n = 10). We conclude that decreased expression of PDGF-beta receptors in the dorsocaudal brain stem correlates with the magnitude of VAH. We speculate that the decreased expression of PDGF-beta receptors is mediated via internalization and degradation of the receptor rather than by transcriptional regulation.

Fluctuations of the fractal dimension of the electroencephalogram during periodic breathing in heart failure patients.

PubMed

Maestri, Roberto; La Rovere, Maria Teresa; Robbi, Elena; Pinna, Gian Domenico

2010-06-01

The physiological mechanisms responsible for periodic breathing (PB) in heart failure (HF) patients are still debated. A role for rhythmic shifts in the level of wakefulness has been suggested, but their existence has never been proven. In this study we investigated the existence of an oscillation in EEG activity during PB in these patients and assessed its relationship with the ventilatory oscillation. EEG activity was measured by the fractal dimension (FD) and by a spectral technique (weighted mean frequency, WMF) in 17 stable HF patients (mean age +/- SD: 57+/-10 yrs, NYHA class: 2.6 +/- 0.4, LVEF: 24 +/- 6%), with sustained PB during supine rest. The relationship between minute ventilation (MV) signal and FD and WMF was assessed by coherence analysis. Most patients (10/17) showed a well defined oscillation in FD and WMF at the frequency of PB closely linked (coherence > 0.7) with the oscillation of MV. In the remaining patients, neither FD nor WMF showed a clear oscillatory pattern synchronous with MV. Overall, the two EEG-derived parameters showed the same coherence with the ventilatory oscillation (mean coherence +/- SD: 0.65 +/- 0.25 vs 0.66 +/- 0.23, for FD and WMF respectively, p = 0.44). Our results provide evidence that during PB in HF patients, EEG activity often, but not always, fluctuates synchronously with the ventilatory oscillation. These fluctuations can be effectively detected by the fractal dimension, but classical spectral methods provide substantially the same information. Other mechanisms, particularly chemical instability in the respiratory control system, are likely to play a role in the genesis of PB.

Tetrodotoxin as a Tool to Elucidate Sensory Transduction Mechanisms: The Case for the Arterial Chemoreceptors of the Carotid Body

PubMed Central

Rocher, Asuncion; Caceres, Ana Isabel; Obeso, Ana; Gonzalez, Constancio

2011-01-01

Carotid bodies (CBs) are secondary sensory receptors in which the sensing elements, chemoreceptor cells, are activated by decreases in arterial PO2 (hypoxic hypoxia). Upon activation, chemoreceptor cells (also known as Type I and glomus cells) increase their rate of release of neurotransmitters that drive the sensory activity in the carotid sinus nerve (CSN) which ends in the brain stem where reflex responses are coordinated. When challenged with hypoxic hypoxia, the physiopathologically most relevant stimulus to the CBs, they are activated and initiate ventilatory and cardiocirculatory reflexes. Reflex increase in minute volume ventilation promotes CO2 removal from alveoli and a decrease in alveolar PCO2 ensues. Reduced alveolar PCO2 makes possible alveolar and arterial PO2 to increase minimizing the intensity of hypoxia. The ventilatory effect, in conjunction the cardiocirculatory components of the CB chemoreflex, tend to maintain an adequate supply of oxygen to the tissues. The CB has been the focus of attention since the discovery of its nature as a sensory organ by de Castro (1928) and the discovery of its function as the origin of ventilatory reflexes by Heymans group (1930). A great deal of effort has been focused on the study of the mechanisms involved in O2 detection. This review is devoted to this topic, mechanisms of oxygen sensing. Starting from a summary of the main theories evolving through the years, we will emphasize the nature and significance of the findings obtained with veratridine and tetrodotoxin (TTX) in the genesis of current models of O2-sensing. PMID:22363245

Hyperventilation and blood acid-base balance in hypercapnia exposed red drum (Sciaenops ocellatus).

PubMed

Ern, Rasmus; Esbaugh, Andrew J

2016-05-01

Hyperventilation is a common response in fish exposed to elevated water CO2. It is believed to lessen the respiratory acidosis associated with hypercapnia by lowering arterial PCO2, but the contribution of hyperventilation to blood acid-base compensation has yet to be quantified. Hyperventilation may also increase the flux of irons across the gill epithelium and the cost of osmoregulation, owing to the osmo-respiratory compromise. Therefore, hypercapnia exposed fish may increase standard metabolic rate (SMR) leaving less energy for physiological functions such as foraging, migration, growth and reproduction. Here we show that gill ventilation, blood PCO2 and total blood [CO2] increased in red drum (Sciaenops ocellatus) exposed to 1000 and 5000 µatm water CO2, and that blood PCO2 and total blood [CO2] decrease in fish during hypoxia induced hyperventilation. Based on these results we estimate the ventilatory contributions to total acid-base compensation in 1000 and 5000 µatm water CO2. We find that S. ocellatus only utilize a portion of its ventilatory capacity to reduce the acid-base disturbance in 1000 µatm water CO2. SMR was unaffected by both salinity and hypercapnia exposure indicating that the cost of osmoregulation is small relative to SMR, and that the lack of increased ventilation in 1000 µatm water CO2 despite the capacity to do so is not due to an energetic tradeoff between acid-base balance and osmoregulation. Therefore, while ocean acidification may impact ventilatory parameters, there will be little impact on the overall energy budget of S. ocellatus.

Effect of Same-day Sequential Exposure to Nitrogen Dioxide and Ozone on Cardiac and Ventilatory Function in Mice

EPA Science Inventory

This study examines the cardiac and ventilatory effects of sequential exposure to nitrogen dioxide and then ozone. The data show that mice exposed to both gases have increased arrhythmia and breathing changes not observed in the other groups. Although the mechanisms underlying ai...

Pulmonary rehabilitation improves cardiovascular response to exercise in COPD.

PubMed

Ramponi, Sara; Tzani, Panagiota; Aiello, Marina; Marangio, Emilio; Clini, Enrico; Chetta, Alfredo

2013-01-01

Pulmonary rehabilitation (PR) has emerged as a recommended standard of care in symptomatic COPD. We now studied whether PR may affect cardiovascular response to exercise in these patients. Twenty-seven patients (9 females aged 69 ± 8 years) with moderate-to-severe airflow obstruction admitted to a 9-week PR course performed a pre-to-post evaluation of lung function test and symptom-limited cardiopulmonary exercise test (CPET). Oxygen uptake (VO2), tidal volume (V(T)), dyspnea and leg fatigue scores were measured during CPET. Cardiovas-cular response was assessed by means of oxygen pulse (O2Pulse), the oxygen uptake efficiency slope and heart rate recovery at the 1st min. A significant increase in peak VO2 and in all cardiovascular parameters (p < 0.05) was found following PR when compared to baseline. Leg fatigue (p < 0.05), but not dyspnea, was significantly reduced after PR. When assessed at metabolic and ventilatory iso levels [% VCO2max and % minute ventilation (VEmax)], O2Pulse and V(T) were significantly higher (p < 0.05) at submaximal exercise (75 and 50% of VCO2max and VEmax) after PR when compared to baseline. V(T) percent changes at 75% VCO2max and 75% VEmax after PR significantly correlated with corresponding changes in O2Pulse (p < 0.01). In COPD patients, a PR training program improved the cardiovascular response during exercise at submaximal exercise independent of the external workload. This change was associated with an enhanced ventilatory function during exercise. Copyright © 2013 S. Karger AG, Basel.

New perspectives concerning feedback influences on cardiorespiratory control during rhythmic exercise and on exercise performance

PubMed Central

Dempsey, Jerome A

2012-01-01

The cardioaccelerator and ventilatory responses to rhythmic exercise in the human are commonly viewed as being mediated predominantly via feedforward ‘central command’ mechanisms, with contributions from locomotor muscle afferents to the sympathetically mediated pressor response. We have assessed the relative contributions of three types of feedback afferents on the cardiorespiratory response to voluntary, rhythmic exercise by inhibiting their normal ‘tonic’ activity in healthy animals and humans and in chronic heart failure. Transient inhibition of the carotid chemoreceptors during moderate intensity exercise reduced muscle sympathetic nerve activity (MSNA) and increased limb vascular conductance and blood flow; and reducing the normal level of respiratory muscle work during heavier intensity exercise increased limb vascular conductance and blood flow. These cardiorespiratory effects were prevented via ganglionic blockade and were enhanced in chronic heart failure and in hypoxia. Blockade of μ opioid sensitive locomotor muscle afferents, with preservation of central motor output via intrathecal fentanyl: (a) reduced the mean arterial blood pressure (MAP), heart rate and ventilatory responses to all steady state exercise intensities; and (b) during sustained high intensity exercise, reduced O2 transport, increased central motor output and end-exercise muscle fatigue and reduced endurance performance. We propose that these three afferent reflexes – probably acting in concert with feedforward central command – contribute significantly to preserving O2 transport to locomotor and to respiratory muscles during exercise. Locomotor muscle afferents also appear to provide feedback concerning the metabolic state of the muscle to influence central motor output, thereby limiting peripheral fatigue development. PMID:22826128

Postural control after a prolonged treadmill run at individual ventilatory and anaerobic threshold.

PubMed

Guidetti, Laura; Franciosi, Emanuele; Gallotta, Maria Chiara; Emerenziani, Gian Pietro; Baldari, Carlo

2011-01-01

The objective of the study was to verify whether young males' balance was affected by 30min prolonged treadmill running (TR) at individual ventilatory (IVT) and anaerobic (IAT) thresholds in recovery time. The VO2max, IAT and IVT during an incremental TR were determined. Mean displacement amplitude (Acp) and velocity (Vcp) of center of pressure were recorded before (pre) and after (0min post; 5min post; and 10min post) prolonged TR at IAT and IVT, through posturographic trials performed with eyes open (EO) and closed (EC). Significant differences between IVT and IAT for Vcp, between EO and EC for Acp and Vcp, were observed. The IAT induced higher destabilizing effect when postural trials were performed with EC. The IVT intensity produced also a destabilizing effect on postural control immediately after exercise. An impairment of postural control after prolonged treadmill running exercise at IVT and IAT intensity was showed. However, destabilizing effect on postural control disappeared within 10min after IAT intensity and within 5min after IVT intensity. Key pointsTo verify whether young males' balance was affected by 30min prolonged treadmill running at individual ventilatory and anaerobic thresholds in recovery time.Mean displacement amplitude and velocity of foot pressure center were recorded before and after prolonged treadmill running at individual ventilatory and anaerobic thresholds, through posturographic trials performed with eyes open and closed.Destabilizing effect on postural control disappeared within 10min post individual anaerobic threshold, and within 5min post individual ventilatory threshold.

α4-Containing nicotinic receptors contribute to the effects of perinatal nicotine on ventilatory and metabolic responses of neonatal mice to ambient cooling.

PubMed

Avraam, Joanne; Cummings, Kevin J; Frappell, Peter B

2016-10-01

Among numerous studies, perinatal nicotine exposure (PN) has had variable effects on respiratory control in the neonatal period. The effects of acute nicotine exposure on breathing are largely mediated by α4-containing nicotine acetylcholine receptors (nAChRs). These receptors are also involved in thermoregulatory responses induced by both acetylcholine and nicotine. We therefore hypothesized that α4-containing nAChRs would mediate the effects of PN on the metabolic and ventilatory responses of neonates to modest cold exposure. Wild-type (WT) and α4 knockout (KO) mice were exposed to 6 mg·kg -1 ·day -1 nicotine or vehicle from embryonic day 14 At postnatal day (P) 7 mice were cooled from an ambient temperature (T A ) of 32 to 20°C. Body temperature (T B ), rate of O 2 consumption (V̇o 2 ), ventilation (V̇e), respiratory frequency (F B ), and tidal volume (V T ) were continually monitored. An absence of α4 had no effect on the metabolic response to ambient cooling. Surprisingly, PN selectively increased the metabolic response of KO pups to cooling. Regardless, KO pups became hypothermic to the same degree as WT pups, and for both genotypes the drop in T B was exacerbated by PN. PN led to hyperventilation in WT pups caused by an increase in V T , an effect that was absent in α4 KO littermates. We show that PN interacts with α4-containing nAChRs in unique ways to modulate the control of breathing and thermoregulation in the early postnatal period. Copyright © 2016 the American Physiological Society.

Measuring Ventilatory Activity with Structured Light Plethysmography (SLP) Reduces Instrumental Observer Effect and Preserves Tidal Breathing Variability in Healthy and COPD

PubMed Central

Niérat, Marie-Cécile; Dubé, Bruno-Pierre; Llontop, Claudia; Bellocq, Agnès; Layachi Ben Mohamed, Lila; Rivals, Isabelle; Straus, Christian; Similowski, Thomas; Laveneziana, Pierantonio

2017-01-01

The use of a mouthpiece to measure ventilatory flow with a pneumotachograph (PNT) introduces a major perturbation to breathing (“instrumental/observer effect”) and suffices to modify the respiratory behavior. Structured light plethysmography (SLP) is a non-contact method of assessment of breathing pattern during tidal breathing. Firstly, we validated the SLP measurements by comparing timing components of the ventilatory pattern obtained by SLP vs. PNT under the same condition; secondly, we compared SLP to SLP+PNT measurements of breathing pattern to evaluate the disruption of breathing pattern and breathing variability in healthy and COPD subjects. Measurements were taken during tidal breathing with SLP alone and SLP+PNT recording in 30 COPD and healthy subjects. Measurements included: respiratory frequency (Rf), inspiratory, expiratory, and total breath time/duration (Ti, Te, and Tt). Passing-Bablok regression analysis was used to evaluate the interchangeability of timing components of the ventilatory pattern (Rf, Ti, Te, and Tt) between measurements performed under the following experimental conditions: SLP vs. PNT, SLP+PNT vs. SLP, and SLP+PNT vs. PNT. The variability of different ventilatory variables was assessed through their coefficients of variation (CVs). In healthy: according to Passing-Bablok regression, Rf, TI, TE and TT were interchangeable between measurements obtained under the three experimental conditions (SLP vs. PNT, SLP+PNT vs. SLP, and SLP+PNT vs. PNT). All the CVs describing “traditional” ventilatory variables (Rf, Ti, Te, Ti/Te, and Ti/Tt) were significantly smaller in SLP+PNT condition. This was not the case for more “specific” SLP-derived variables. In COPD: according to Passing-Bablok regression, Rf, TI, TE, and TT were interchangeable between measurements obtained under SLP vs. PNT and SLP+PNT vs. PNT, whereas only Rf, TE, and TT were interchangeable between measurements obtained under SLP+PNT vs. SLP. However, most discrete variables were significantly different between the SLP and SLP+PNT conditions and CVs were significantly lower when COPD patients were assessed in the SLP+PNT condition. Measuring ventilatory activity with SLP preserves resting tidal breathing variability, reduces instrumental observer effect and avoids any disruptions in breathing pattern induced by the use of PNT-mouthpiece-nose-clip combination. PMID:28572773

Measuring Ventilatory Activity with Structured Light Plethysmography (SLP) Reduces Instrumental Observer Effect and Preserves Tidal Breathing Variability in Healthy and COPD.

PubMed

Niérat, Marie-Cécile; Dubé, Bruno-Pierre; Llontop, Claudia; Bellocq, Agnès; Layachi Ben Mohamed, Lila; Rivals, Isabelle; Straus, Christian; Similowski, Thomas; Laveneziana, Pierantonio

2017-01-01

The use of a mouthpiece to measure ventilatory flow with a pneumotachograph (PNT) introduces a major perturbation to breathing ("instrumental/observer effect") and suffices to modify the respiratory behavior. Structured light plethysmography (SLP) is a non-contact method of assessment of breathing pattern during tidal breathing. Firstly, we validated the SLP measurements by comparing timing components of the ventilatory pattern obtained by SLP vs. PNT under the same condition; secondly, we compared SLP to SLP+PNT measurements of breathing pattern to evaluate the disruption of breathing pattern and breathing variability in healthy and COPD subjects. Measurements were taken during tidal breathing with SLP alone and SLP+PNT recording in 30 COPD and healthy subjects. Measurements included: respiratory frequency (R f ), inspiratory, expiratory, and total breath time/duration (Ti, Te, and Tt). Passing-Bablok regression analysis was used to evaluate the interchangeability of timing components of the ventilatory pattern (R f , Ti, Te, and Tt) between measurements performed under the following experimental conditions: SLP vs. PNT, SLP+PNT vs. SLP, and SLP+PNT vs. PNT. The variability of different ventilatory variables was assessed through their coefficients of variation (CVs). In healthy: according to Passing-Bablok regression, Rf, TI, TE and TT were interchangeable between measurements obtained under the three experimental conditions (SLP vs. PNT, SLP+PNT vs. SLP, and SLP+PNT vs. PNT). All the CVs describing "traditional" ventilatory variables (R f , Ti, Te, Ti/Te, and Ti/Tt) were significantly smaller in SLP+PNT condition. This was not the case for more "specific" SLP-derived variables. In COPD: according to Passing-Bablok regression, Rf, TI, TE, and TT were interchangeable between measurements obtained under SLP vs. PNT and SLP+PNT vs. PNT, whereas only Rf, TE, and TT were interchangeable between measurements obtained under SLP+PNT vs. SLP. However, most discrete variables were significantly different between the SLP and SLP+PNT conditions and CVs were significantly lower when COPD patients were assessed in the SLP+PNT condition. Measuring ventilatory activity with SLP preserves resting tidal breathing variability, reduces instrumental observer effect and avoids any disruptions in breathing pattern induced by the use of PNT-mouthpiece-nose-clip combination.

Intermittent hypoxia increases arterial blood pressure in humans through a Renin-Angiotensin system-dependent mechanism.

PubMed

Foster, Glen E; Hanly, Patrick J; Ahmed, Sofia B; Beaudin, Andrew E; Pialoux, Vincent; Poulin, Marc J

2010-09-01

Intermittent hypoxia (IH) is believed to contribute to the pathogenesis of hypertension in obstructive sleep apnea through mechanisms that include activation of the renin-angiotensin system. The objective of this study was to assess the role of the type I angiotensin II receptor in mediating an increase in arterial pressure associated with a single 6-hour IH exposure. Using a double-blind, placebo-controlled, randomized, crossover study design, we exposed 9 healthy male subjects to sham IH, IH with placebo medication, and IH with the type I angiotensin II receptor antagonist losartan. We measured blood pressure, cerebral blood flow, and ventilation at baseline and after exposure to 6 hours of IH. An acute isocapnic hypoxia experimental protocol was conducted immediately before and after exposure to IH. IH with placebo increased resting mean arterial pressure by 7.9+/-1.6 mm Hg, but mean arterial pressure did not increase with sham IH (1.9+/-1.5 mm Hg) or with losartan IH (-0.2+/-2.4 mm Hg; P<0.05). Exposure to IH prevented the diurnal decrease in the cerebral blood flow response to hypoxia, independently of the renin-angiotensin system. Finally, in contrast to other models of IH, the acute hypoxic ventilatory response did not change throughout the protocol. IH increases arterial blood pressure through activation of the type I angiotensin II receptor, without a demonstrable impact on the cerebrovascular or ventilatory response to acute hypoxia.

Postdoctoral Fellowship for Dr. Lindholm, Underwater Physiology and Medicine

DTIC Science & Technology

2008-05-01

St Croix 2000) and/or an increased reliance on fast twitch muscle fibers that are dependent on glycogen and produce La. The changes in muscle and...resistance protocol ( isometric ) increases respiratory muscle strength but not endurance, while, a protocol designed to increase respiratory muscle endurance... muscles (RMT). RMT minimized respiratory muscle fatigue and normalized the ventilatory response to increasing C02 (C02 sensitivity) and blood C02 in C02

Differential impacts of ocean acidification and warming on winter and summer progeny of a coastal squid (Loligo vulgaris).

PubMed

Rosa, Rui; Trübenbach, Katja; Pimentel, Marta S; Boavida-Portugal, Joana; Faleiro, Filipa; Baptista, Miguel; Dionísio, Gisela; Calado, Ricardo; Pörtner, Hans O; Repolho, Tiago

2014-02-15

Little is known about the capacity of early life stages to undergo hypercapnic and thermal acclimation under the future scenarios of ocean acidification and warming. Here, we investigated a comprehensive set of biological responses to these climate change-related variables (2°C above winter and summer average spawning temperatures and ΔpH=0.5 units) during the early ontogeny of the squid Loligo vulgaris. Embryo survival rates ranged from 92% to 96% under present-day temperature (13-17°C) and pH (8.0) scenarios. Yet, ocean acidification (pH 7.5) and summer warming (19°C) led to a significant drop in the survival rates of summer embryos (47%, P<0.05). The embryonic period was shortened by increasing temperature in both pH treatments (P<0.05). Embryo growth rates increased significantly with temperature under present-day scenarios, but there was a significant trend reversal under future summer warming conditions (P<0.05). Besides pronounced premature hatching, a higher percentage of abnormalities was found in summer embryos exposed to future warming and lower pH (P<0.05). Under the hypercapnic scenario, oxygen consumption rates decreased significantly in late embryos and newly hatched paralarvae, especially in the summer period (P<0.05). Concomitantly, there was a significant enhancement of the heat shock response (HSP70/HSC70) with warming in both pH treatments and developmental stages. Upper thermal tolerance limits were positively influenced by acclimation temperature, and such thresholds were significantly higher in late embryos than in hatchlings under present-day conditions (P<0.05). In contrast, the upper thermal tolerance limits under hypercapnia were higher in hatchlings than in embryos. Thus, we show that the stressful abiotic conditions inside the embryo's capsules will be exacerbated under near-future ocean acidification and summer warming scenarios. The occurrence of prolonged embryogenesis along with lowered thermal tolerance limits under such conditions is expected to negatively affect the survival success of squid early life stages during the summer spawning period, but not winter spawning.

Acid-base balance and changes in haemolymph properties of the South African rock lobsters, Jasus lalandii, a palinurid decapod, during chronic hypercapnia.

PubMed

Knapp, Jarred L; Bridges, Christopher R; Krohn, Janina; Hoffman, Louwrens C; Auerswald, Lutz

2015-06-05

Few studies exist reporting on long-term exposure of crustaceans to hypercapnia. We exposed juvenile South African rock lobsters, Jasus lalandii, to hypercapnic conditions of pH 7.3 for 28 weeks and subsequently analysed changes in the extracellular fluid (haemolymph). Results revealed, for the first time, adjustments in the haemolymph of a palinurid crustacean during chronic hypercapnic exposure: 1) acid-base balance was adjusted and sustained by increased bicarbonate and 2) quantity and oxygen binding properties of haemocyanin changed. Compared with lobsters kept under normocapnic conditions (pH 8.0), during prolonged hypercapnia, juvenile lobsters increased bicarbonate buffering of haemolymph. This is necessary to provide optimum pH conditions for oxygen binding of haemocyanin and functioning of respiration in the presence of a strong Bohr Effect. Furthermore, modification of the intrinsic structure of the haemocyanin molecule, and not the presence of molecular modulators, seems to improve oxygen affinity under conditions of elevated pCO2. Copyright © 2015 Elsevier Inc. All rights reserved.

Intertidal pool fish Girella laevifrons (Kyphosidae) shown strong physiological homeostasis but shy personality: The cost of living in hypercapnic habitats.

PubMed

Benítez, S; Duarte, C; Opitz, T; Lagos, N A; Pulgar, J M; Vargas, C A; Lardies, M A

2017-05-15

Tide pools habitats are naturally exposed to a high degree of environmental variability. The consequences of living in these extreme habitats are not well established. In particular, little it is known about of the effects of hypercanic seawater (i.e. high pCO 2 levels) on marine vertebrates such as intertidal pool fish. The aim of this study was to evaluate the effects of increased pCO 2 on the physiology and behavior in juveniles of the intertidal pool fish Girella laevifrons. Two nominal pCO 2 concentrations (400 and 1600μatm) were used. We found that exposure to hypercapnic conditions did not affect oxygen consumption and absorption efficiency. However, the lateralization and boldness behavior was significantly disrupted in high pCO 2 conditions. In general, a predator-risk cost of boldness is assumed, thus the increased occurrence of shy personality in juvenile fishes may result in a change in the balance of this biological interaction, with significant ecological consequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of cycling history on the ventilatory response to cycle-ergometry in humans: a role for respiratory memory?

PubMed

Cathcart, Andrew J; Whipp, Brian J; Turner, Anthony P; Wilson, John; Ward, Susan A

2010-01-01

The ventilatory (V' E) mechanisms subserving stability of alveolar and arterial PCO2 (PACO2, PaCO2) during moderate exercise (< lactate threshold, thetaL) remain controversial. As long-term modulation has been argued to be an important contributor to this control process, we proposed that subjects with no experience of cycling (NEx) might provide insight into this issue. With no exercise familiarization, 9 sedentary NEx subjects and 9 age-, sex-, and activity-matched controls (C) who had cycled regularly for recreational purposes since childhood completed a square-wave (6-min stage) cycle-ergometry test: 10 W-WR1-WR2-WR1-10 W; WR1 range 25-45 W, WR2 range 50-90 W. WRs were subsequently confirmed to

Hypercapnia-Induced Amelioration of the Intestinal Microvascular Oxygenation in Sepsis is Independent of the Endogenous Sympathetic Nervous System.

PubMed

Schulz, Jan; Schöneborn, Sabrina; Vollmer, Christian; Truse, Richard; Herminghaus, Anna; Bauer, Inge; Beck, Christopher; Picker, Olaf

2018-03-01

Insufficient microvascular oxygenation (μHBO2) of the intestinal mucosa worsens outcome of septic patients. Hypercapnia ameliorates μHBO2, mediated via endogenous vasopressin release. Under physiological conditions, blockade of the endogenous sympathetic nervous system abolishes this protective effect of hypercapnia. The aim of our study was therefore to evaluate the role of the endogenous sympathetic nervous system during hypercapnia on intestinal μHBO2 under septic conditions. We randomized 80 male Wistar rats into eight groups. Sepsis was induced via colon ascendens stent peritonitis. The animals were subjected to 120 min of normocapnic (pCO2 35 mm Hg-45 mm Hg) or moderate hypercapnic (pCO2 65 mm Hg-75 mm Hg) ventilation 24 h after surgery. Animals received sympathetic blockade (hexamethonium 15 mg · kg (bolus) followed by 15 mg · kg · h (infusion) intravenously) or the same volume as vehicle (NaCl 0.9%). Microcirculatory oxygenation (μHBO2) and perfusion (μflow) were recorded using tissue reflectance spectrophotometry and laser Doppler. In septic animals, μHBO2 decreased during normocapnia (-8.9 ± 4%) and increased during hypercapnia (+7.8 ± 7.5%). The additional application of hexamethonium did not influence these effects. μHBO2 declined in normocapnic septic animals treated with hexamethonium similar to normocapnia alone (-6.1 ± 5.4%) and increased in hypercapnic animals treated with hexamethonium similar to hypercapnia alone (+7.9 ± 11.7%). Furthermore, hypercapnic ventilation ameliorated microcirculatory perfusion (μflow) irrespective of whether animals received hexamethonium (from 113 ± 54 [AU] to 206 ± 87 [AU]) or vehicle (from 97 ± 37 [AU]-169 ± 52 [AU]). The amelioration of the intestinal microcirculation during hypercapnia in sepsis is independent of the endogenous sympathetic nervous system.

Non-Invasive Ventilation (NIV) and Homeostatic Model Assessment (HOMA) Index in Stable Chronic Obstructive Pulmonary Disease (COPD) Patients with Chronic Hypercapnic Respiratory Failure: A Pilot Study.

PubMed

Dimoulis, Andreas; Pastaka, Chaido; Tsolaki, Vasiliki; Tsilioni, Irini; Pournaras, Spyridon; Liakos, Nikolaos; Georgoulias, Panagiotis; Gourgoulianis, Konstantinos

2015-08-01

The effects of Non-invasive Ventilation (NIV) on Insulin Resistance (IR) in stable Chronic Obstructive Pulmonary Disease (COPD) patients have not been fully explored. The aim of this study was to assess the effects of NIV on IR and adiponectin levels during one year application of NIV in stable COPD patients with Chronic Hypercapnic Respiratory Failure. Twenty-five (25) stable COPD patients with Chronic Hypercapnic Respiratory Failure and with no self-reported comorbidities completed the study. NIV was administered in the spontaneous/timed mode via a full face mask using a bi-level positive airway pressure system. Spirometry, blood pressure, arterial blood gases, dyspnea, daytime sleepiness, serum fasting glucose and insulin levels were assessed. IR was assessed with the calculation of the Homeostatic Model Assessment (HOMA) index. Adiponectin was measured with radioimmunoassay. Study participants were re-evaluated on the first, third, sixth, ninth and twelfth month after the initial evaluation. There was a significant improvement in FEV1 values from the first month (34.1 ± 11.6% vs 37 ± 12.3%, p = 0.05). There was a significant decrease in IR by the ninth month of NIV use (3.4 ± 2.3 vs 2.2 ± 1.4, p < 0.0001), while adiponectin levels significantly improved from the first month of NIV use. Stepwise regression analysis revealed that baseline HOMA index was associated with paCO2 (β = 0.07 ± 0.02, p = 0.001), while baseline adiponectin levels were associated with FVC (β = 0.05 ± 0.02, p = 0.035) and the concentration of serum bicarbonate (HCO3-) (-β = 0.18 ± 0.06, p = 0.002). Insulin sensitivity and glucose metabolism as well as adiponectin levels improved along with the improvements in respiratory failure.

EFFECTS OF INDUCED RESPIRATORY CHANGES ON CARDIAC, VENTILATORY, AND THERMOREGULATORY PARAMETERS IN HEALTHY SPRAGUE-DAWLEY RATS

EPA Science Inventory

EFFECTS OF INDUCED RESPIRATORY CHANGES ON CARDIAC, VENTILATORY, AND THERMOREGULATORY PARAMETERS IN HEALTHY SPRAGUE-DAWLEY RATS. LB Wichers1, WH Rowan2, DL Costa2, MJ Campen3 and WP Watkinson2 1UNC SPH, Chapel Hill, NC, USA; 2USEPA, ORD/NHEERL/ETD/PTB, RTP, NC, USA; 3LRRI, A...

Muscular, cardiac, ventilatory and metabolic dysfunction in patients with multiple sclerosis: Implications for screening, clinical care and endurance and resistance exercise therapy, a scoping review.

PubMed

Wens, Inez; Eijnde, Bert O; Hansen, Dominique

2016-08-15

In the treatment of multiple sclerosis (MS), exercise training is now considered a cornerstone. However, most clinicians tend to focus on neurologic deficits only, and thus prefer to prescribe rehabilitation programs specifically to counteract these deficits. However, the present comprehensive review shows that patients with MS (pwMS) also experience significant muscular, cardiac, ventilatory and metabolic dysfunction, which significantly contribute, next to neurologic deficits, to exercise intolerance. In addition, these anomalies also might increase the risk for frequent hospitalization and morbidity and can reduce life expectancy. Unfortunately, the impact of exercise intervention on these anomalies in pwMS are mostly unknown. Therefore, it is suggested that pwMS should be screened systematically for muscular, cardiac, ventilatory and metabolic function during exercise testing. The detection of such anomalies should lead to adaptations and optimisation of exercise training prescription and clinical care/medical treatment of pwMS. In addition, future studies should focus on the impact of exercise intervention on muscular, cardiac, ventilatory and metabolic (dys)function in pwMS, to contribute to improved treatment and care. Copyright © 2016. Published by Elsevier B.V.

Anaerobic threshold determination through ventilatory and electromyographics parameters.

PubMed

Gassi, E R; Bankoff, A D P

2010-01-01

The aim of present study was to compare the alterations in electromyography signs with Ventilatory Threshold (VT). Had been part of the study eight men, amateur cyclists and triathletes (25.25 +/- 6.96 years), that they had exercised themselves in a mechanical cicloergometer, a cadence of 80 RPM and with the increased intensity being in 25 W/min until the exhaustion. The VT was determined by a non-linear increase in VE/VO2 without any increase in VE/VCO2 and compared with the intensity corresponding to break point of amplitude EMG sign during the incremental exercise. The EMG--Fatigue Threshold (FT) and Ventilatory Threshold (VT) parameters used were the power, the time, absolute and relative VO2, ventilation (VE), the heart hate (HH) and the subjective perception of the effort. The results had not shown to difference in none of the variable selected for the corresponding intensity to VT and FT--EMG of the muscles lateralis vastus and femoris rectus. The parameters used in the comparison between the electromyographic indicators and ventilatory were the load, the time, absolute VO2 and relative to corporal mass, to ventilation (VE), the heart frequency (HH) and the Subjective Perception of the Effort (SPE).

Adrenaline release evokes hyperpnoea and an increase in ventilatory CO2 sensitivity during hypoglycaemia: a role for the carotid body

PubMed Central

Thompson, Emma L.; Ray, Clare J.; Holmes, Andrew P.; Pye, Richard L.; Wyatt, Christopher N.; Kumar, Prem

2016-01-01

Key points Hypoglycaemia is counteracted by release of hormones and an increase in ventilation and CO2 sensitivity to restore blood glucose levels and prevent a fall in blood pH.The full counter‐regulatory response and an appropriate increase in ventilation is dependent on carotid body stimulation.We show that the hypoglycaemia‐induced increase in ventilation and CO2 sensitivity is abolished by preventing adrenaline release or blocking its receptors.Physiological levels of adrenaline mimicked the effect of hypoglycaemia on ventilation and CO2 sensitivity.These results suggest that adrenaline, rather than low glucose, is an adequate stimulus for the carotid body‐mediated changes in ventilation and CO2 sensitivity during hypoglycaemia to prevent a serious acidosis in poorly controlled diabetes. Abstract Hypoglycaemia in vivo induces a counter‐regulatory response that involves the release of hormones to restore blood glucose levels. Concomitantly, hypoglycaemia evokes a carotid body‐mediated hyperpnoea that maintains arterial CO2 levels and prevents respiratory acidosis in the face of increased metabolism. It is unclear whether the carotid body is directly stimulated by low glucose or by a counter‐regulatory hormone such as adrenaline. Minute ventilation was recorded during infusion of insulin‐induced hypoglycaemia (8–17 mIU kg−1 min−1) in Alfaxan‐anaesthetised male Wistar rats. Hypoglycaemia significantly augmented minute ventilation (123 ± 4 to 143 ± 7 ml min−1) and CO2 sensitivity (3.3 ± 0.3 to 4.4 ± 0.4 ml min−1 mmHg−1). These effects were abolished by either β‐adrenoreceptor blockade with propranolol or adrenalectomy. In this hypermetabolic, hypoglycaemic state, propranolol stimulated a rise in P aC O2, suggestive of a ventilation–metabolism mismatch. Infusion of adrenaline (1 μg kg−1 min−1) increased minute ventilation (145 ± 4 to 173 ± 5 ml min−1) without altering P aC O2 or pH and enhanced ventilatory CO2 sensitivity (3.4 ± 0.4 to 5.1 ± 0.8 ml min−1 mmHg−1). These effects were attenuated by either resection of the carotid sinus nerve or propranolol. Physiological concentrations of adrenaline increased the CO2 sensitivity of freshly dissociated carotid body type I cells in vitro. These findings suggest that adrenaline release can account for the ventilatory hyperpnoea observed during hypoglycaemia by an augmented carotid body and whole body ventilatory CO2 sensitivity. PMID:27027261

Adrenaline release evokes hyperpnoea and an increase in ventilatory CO2 sensitivity during hypoglycaemia: a role for the carotid body.

PubMed

Thompson, Emma L; Ray, Clare J; Holmes, Andrew P; Pye, Richard L; Wyatt, Christopher N; Coney, Andrew M; Kumar, Prem

2016-08-01

Hypoglycaemia is counteracted by release of hormones and an increase in ventilation and CO2 sensitivity to restore blood glucose levels and prevent a fall in blood pH. The full counter-regulatory response and an appropriate increase in ventilation is dependent on carotid body stimulation. We show that the hypoglycaemia-induced increase in ventilation and CO2 sensitivity is abolished by preventing adrenaline release or blocking its receptors. Physiological levels of adrenaline mimicked the effect of hypoglycaemia on ventilation and CO2 sensitivity. These results suggest that adrenaline, rather than low glucose, is an adequate stimulus for the carotid body-mediated changes in ventilation and CO2 sensitivity during hypoglycaemia to prevent a serious acidosis in poorly controlled diabetes. Hypoglycaemia in vivo induces a counter-regulatory response that involves the release of hormones to restore blood glucose levels. Concomitantly, hypoglycaemia evokes a carotid body-mediated hyperpnoea that maintains arterial CO2 levels and prevents respiratory acidosis in the face of increased metabolism. It is unclear whether the carotid body is directly stimulated by low glucose or by a counter-regulatory hormone such as adrenaline. Minute ventilation was recorded during infusion of insulin-induced hypoglycaemia (8-17 mIU kg(-1)  min(-1) ) in Alfaxan-anaesthetised male Wistar rats. Hypoglycaemia significantly augmented minute ventilation (123 ± 4 to 143 ± 7 ml min(-1) ) and CO2 sensitivity (3.3 ± 0.3 to 4.4 ± 0.4 ml min(-1)  mmHg(-1) ). These effects were abolished by either β-adrenoreceptor blockade with propranolol or adrenalectomy. In this hypermetabolic, hypoglycaemic state, propranolol stimulated a rise in P aC O2, suggestive of a ventilation-metabolism mismatch. Infusion of adrenaline (1 μg kg(-1)  min(-1) ) increased minute ventilation (145 ± 4 to 173 ± 5 ml min(-1) ) without altering P aC O2 or pH and enhanced ventilatory CO2 sensitivity (3.4 ± 0.4 to 5.1 ± 0.8 ml min(-1)  mmHg(-1) ). These effects were attenuated by either resection of the carotid sinus nerve or propranolol. Physiological concentrations of adrenaline increased the CO2 sensitivity of freshly dissociated carotid body type I cells in vitro. These findings suggest that adrenaline release can account for the ventilatory hyperpnoea observed during hypoglycaemia by an augmented carotid body and whole body ventilatory CO2 sensitivity. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Effects of exercise training on HbA1c and VO2peak in patients with type 2 diabetes and coronary artery disease: A randomised clinical trial.

PubMed

Byrkjeland, Rune; Njerve, Ida U; Anderssen, Sigmund; Arnesen, Harald; Seljeflot, Ingebjørg; Solheim, Svein

2015-09-01

Few exercise trials have focused on patients with both type 2 diabetes and coronary artery disease. We investigated the effects of 1 year of exercise training on HbA1c and VO(2peak) in these patients. Patients with type 2 diabetes and coronary artery disease (n = 137) were randomised to combined exercise training or control group. HbA(1c) was measured at the beginning and end of the study. Changes in VO(2peak), and also ventilatory threshold and time to exhaustion, were assessed by cardiopulmonary exercise testing. No differences in changes between the randomised groups were observed in HbA1c and VO(2peak), whereas ventilatory threshold and time to exhaustion increased significantly in the exercise group compared with the controls (p = 0.046 and p = 0.034). In patients without previous acute myocardial infarction and diabetes microvascular complications (n = 46), the exercise group did improve HbA1c and VO(2peak) compared with the controls (p = 0.052 and p = 0.035). No significant effects of exercise training on HbA(1c) or VO(2peak) were observed in patients with type 2 diabetes and coronary artery disease, although improvements were seen in patients without vascular complications beyond coronary artery disease, implying that the degree of vascular disease may influence exercise responses. Ventilatory threshold and time to exhaustion did increase significantly, indicating improved exercise performance despite the minor change in VO(2peak). © The Author(s) 2015.

Relationship between arterial oxygen desaturation and ventilation during maximal exercise.

PubMed

Miyachi, M; Tabata, I

1992-12-01

The purpose of the present study was to investigate the contribution of ventilation to arterial O2 desaturation during maximal exercise. Nine untrained subjects and 22 trained long-distance runners [age 18-36 yr, maximal O2 uptake (VO2max) 48-74 ml.min-1 x kg-1] volunteered to participate in the study. The subjects performed an incremental exhaustive cycle ergometry test at 70 rpm of pedaling frequency, during which arterial O2 saturation (SaO2) and ventilatory data were collected every minute. SaO2 was estimated with a pulse oximeter. A significant positive correlation was found between SaO2 and end-tidal PO2 (PETO2; r = 0.72, r2 = 0.52, P < 0.001) during maximal exercise. These statistical results suggest that approximately 50% of the variability of SaO2 can be accounted for by differences in PETO2, which reflects alveolar PO2. Furthermore, PETO2 was highly correlated with the ventilatory equivalent for O2 (VE/VO2; r = 0.91, P < 0.001), which indicates that PETO2 could be the result of ventilation stimulated by maximal exercise. Finally, SaO2 was positively related to VE/VO2 during maximal exercise (r = 0.74, r2 = 0.55, P < 0.001). Therefore, one-half of the arterial O2 desaturation occurring during maximal exercise may be explained by less hyperventilation, specifically for our subjects, who demonstrated a wide range of trained states. Furthermore, we found an indirect positive correlation between SaO2 and ventilatory response to CO2 at rest (r = 0.45, P < 0.05), which was mediated by ventilation during maximal exercise. These data also suggest that ventilation is an important factor for arterial O2 desaturation during maximal exercise.

Identification and agreement of first turn point by mathematical analysis applied to heart rate, carbon dioxide output and electromyography

PubMed Central

Zamunér, Antonio R.; Catai, Aparecida M.; Martins, Luiz E. B.; Sakabe, Daniel I.; Silva, Ester Da

2013-01-01

Background The second heart rate (HR) turn point has been extensively studied, however there are few studies determining the first HR turn point. Also, the use of mathematical and statistical models for determining changes in dynamic characteristics of physiological variables during an incremental cardiopulmonary test has been suggested. Objectives To determine the first turn point by analysis of HR, surface electromyography (sEMG), and carbon dioxide output () using two mathematical models and to compare the results to those of the visual method. Method Ten sedentary middle-aged men (53.9±3.2 years old) were submitted to cardiopulmonary exercise testing on an electromagnetic cycle ergometer until exhaustion. Ventilatory variables, HR, and sEMG of the vastus lateralis were obtained in real time. Three methods were used to determine the first turn point: 1) visual analysis based on loss of parallelism between and oxygen uptake (); 2) the linear-linear model, based on fitting the curves to the set of data (Lin-Lin ); 3) a bi-segmental linear regression of Hinkley' s algorithm applied to HR (HMM-HR), (HMM- ), and sEMG data (HMM-RMS). Results There were no differences between workload, HR, and ventilatory variable values at the first ventilatory turn point as determined by the five studied parameters (p>0.05). The Bland-Altman plot showed an even distribution of the visual analysis method with Lin-Lin , HMM-HR, HMM-CO2, and HMM-RMS. Conclusion The proposed mathematical models were effective in determining the first turn point since they detected the linear pattern change and the deflection point of , HR responses, and sEMG. PMID:24346296

Identification and agreement of first turn point by mathematical analysis applied to heart rate, carbon dioxide output and electromyography.

PubMed

Zamunér, Antonio R; Catai, Aparecida M; Martins, Luiz E B; Sakabe, Daniel I; Da Silva, Ester

2013-01-01

The second heart rate (HR) turn point has been extensively studied, however there are few studies determining the first HR turn point. Also, the use of mathematical and statistical models for determining changes in dynamic characteristics of physiological variables during an incremental cardiopulmonary test has been suggested. To determine the first turn point by analysis of HR, surface electromyography (sEMG), and carbon dioxide output (VCO2) using two mathematical models and to compare the results to those of the visual method. Ten sedentary middle-aged men (53.9 ± 3.2 years old) were submitted to cardiopulmonary exercise testing on an electromagnetic cycle ergometer until exhaustion. Ventilatory variables, HR, and sEMG of the vastus lateralis were obtained in real time. Three methods were used to determine the first turn point: 1) visual analysis based on loss of parallelism between VCO2 and oxygen uptake (VO2); 2) the linear-linear model, based on fitting the curves to the set of VCO2 data (Lin-LinVCO2); 3) a bi-segmental linear regression of Hinkley's algorithm applied to HR (HMM-HR), VCO2 (HMM-VCO2), and sEMG data (HMM-RMS). There were no differences between workload, HR, and ventilatory variable values at the first ventilatory turn point as determined by the five studied parameters (p>0.05). The Bland-Altman plot showed an even distribution of the visual analysis method with Lin-LinVCO2, HMM-HR, HMM-VCO2, and HMM-RMS. The proposed mathematical models were effective in determining the first turn point since they detected the linear pattern change and the deflection point of VCO2, HR responses, and sEMG.

Ventilatory control sensitivity in patients with obstructive sleep apnea is sleep stage dependent.

PubMed

Landry, Shane A; Andara, Christopher; Terrill, Philip I; Joosten, Simon A; Leong, Paul; Mann, Dwayne L; Sands, Scott A; Hamilton, Garun S; Edwards, Bradley A

2018-05-01

The severity of obstructive sleep apnea (OSA) is known to vary according to sleep stage; however, the pathophysiology responsible for this robust observation is incompletely understood. The objective of the present work was to examine how ventilatory control system sensitivity (i.e. loop gain) varies during sleep in patients with OSA. Loop gain was estimated using signals collected from standard diagnostic polysomnographic recordings performed in 44 patients with OSA. Loop gain measurements associated with nonrapid eye movement (NREM) stage 2 (N2), stage 3 (N3), and REM sleep were calculated and compared. The sleep period was also split into three equal duration tertiles to investigate how loop gain changes over the course of sleep. Loop gain was significantly lower (i.e. ventilatory control more stable) in REM (Mean ± SEM: 0.51 ± 0.04) compared with N2 sleep (0.63 ± 0.04; p = 0.001). Differences in loop gain between REM and N3 (p = 0.095), and N2 and N3 (p = 0.247) sleep were not significant. Furthermore, N2 loop gain was significantly lower in the first third (0.57 ± 0.03) of the sleep period compared with later second (0.64 ± 0.03, p = 0.012) and third (0.64 ± 0.03, p = 0.015) tertiles. REM loop gain also tended to increase across the night; however, this trend was not statistically significant [F(2, 12) = 3.49, p = 0.09]. These data suggest that loop gain varies between REM and NREM sleep and modestly increases over the course of sleep. Lower loop gain in REM is unlikely to contribute to the worsened OSA severity typically observed in REM sleep, but may explain the reduced propensity for central sleep apnea in this sleep stage.

[Physiological parameters of breathing and the impact of non-invasive ventilation (NIV) on patients with amyotrophic lateral sclerosis (ALS)].

PubMed

Czudaj, K-P; Suchi, S; Schönhofer, B

2009-12-01

Amyotrophic lateral sclerosis (ALS), as a consequence of the progressive failure of respiratory muscles, often causes chronic ventilatory failure (CVF), indicated by hypercapnia. This study analyses the physiological parameters of breathing in patients with ALS over time and the variables which influence survival time. In this observational study we analysed the data of physiological parameters (respiratory function, blood gas levels and breathing during sleep), as well as survival rate (according to Kaplan-Meier) of all 85 ALS patients who stayed in our hospital during the period of 1st January 2003 until 31st December 2007. After ALS had been diagnosed, all patients ran through standardised pneumological diagnostics during the observation period, this procedure was repeated every 3-6 months. If hypercapnia (carbon dioxide tension pCO(2) > 45 mm Hg) was detected, non-invasive ventilation (NIV) was indicated and offered to the respective patients. In the course of the observation, the parameters of respiratory function IVC (inspiratory vital capacity) and FEV1 (forced expiratory volume after 1 second) have shown a significant reduction by 14-15% per year. Half of the patients died within 3.1 years after ALS had been diagnosed. IVC and FEV1 had no impact on the survival time. In contrast, pCO(2) correlates negatively with the survival time. The period between diagnosis of ALS and manifestation of hypercapnia is about 1.9 +/- 2.4 years. In spite of a clear indication, some of the patients did not comply with NIV or did not accept it (19 patients, 22%). Twenty-eight patients (33%) started NIV with a good compliance. The survival rate of patients with NIV was 1.27 years on average--after the initial measurement of hypercapnia. The survival time of hypercapnic patients without NIV was only 0.12 years. Hypercapnia has a significant impact on the prognosis for ALS patients. In the case of CVF (hypercapnia), the survival time of ALS patients is significantly reduced. NIV is able to significantly increase the survival time of ALS patients with hypercapnia. Georg Thieme Verlag KG Stuttgart-New York.

Effects of maternal high-fat diet and sedentary lifestyle on susceptibility of adult offspring to ozone exposure in rats.

PubMed

Gordon, C J; Phillips, P M; Johnstone, A F M; Schmid, J; Schladweiler, M C; Ledbetter, A; Snow, S J; Kodavanti, U P

2017-05-01

Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O 3 ). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O 3 susceptibility of offspring could thus be manifested by maternal obesity. Thirty-day-old female Long-Evans rats were fed a control (CD) or high-fat (HF) (60% calories) diet for 6 wks and then bred. GD1 rats were then housed with a running wheel (RW) or without a wheel (SED) until parturition, creating four groups of offspring: CD-SED, CD-RW, HF-SED and HF-RW. HF diet was terminated at PND 35 and all offspring were placed on CD. Body weight and %fat of dams were greatest in order; HF-SED > HF-RW > CD-SED > CD-RW. Adult offspring were exposed to O 3 for two consecutive days (0.8 ppm, 4 h/day). Glucose tolerance tests (GTT), ventilatory parameters (plethysmography), and bronchoalveolar fluid (BALF) cell counts and protein biomarkers were performed to assess response to O 3 . Exercise and diet altered body weight and %fat of young offspring. GTT, ventilation and BALF cell counts were exacerbated by O 3 with responses markedly exacerbated in males. HF diet and O 3 led to significant exacerbation of several BALF parameters: total cell count, neutrophils and lymphocytes were increased in male HF-SED versus CD-SED. Males were hyperglycemic after O 3 exposure and exhibited exacerbated GTT responses. Ventilatory dysfunction was also exacerbated in males. Maternal exercise had minimal effects on O 3 response. The results of this exploratory study suggest a link between maternal obesity and susceptibility to O 3 in their adult offspring in a sex-specific manner.

Change in VO2max and time trial performance in response to high-intensity interval training prescribed using ventilatory threshold.

PubMed

Astorino, Todd A; deRevere, Jamie; Anderson, Theodore; Kellogg, Erin; Holstrom, Patrick; Ring, Sebastian; Ghaseb, Nicholas

2018-06-19

Completion of high-intensity interval training (HIIT) leads to significant increases in maximal oxygen uptake (VO 2max ) and oxidative capacity. However, individual responses to HIIT have been identified as approximately 20-40% of individuals show no change in VO 2max , which may be due to the relatively homogeneous approach to implementing HIIT. This study tested the effects of HIIT prescribed using ventilatory threshold (VT) on changes in VO 2max and cycling performance. Fourteen active men and women (age and VO 2max  = 27 ± 8 year and 38 ± 4 mL/kg/min) underwent nine sessions of HIIT, and 14 additional men and women (age and VO 2max  = 22 ± 3 year and 40 ± 5 mL/kg/min) served as controls. Training was performed on a cycle ergometer at a work rate equal to 130%VT and consisted of eight to ten 1 min bouts interspersed with 75 s of recovery. At baseline and post-testing, they completed progressive cycling to exhaustion to determine VO 2max , and on a separate day, a 5 mile cycling time trial. Compared to the control group, HIIT led to significant increases in VO 2max (6%, p = 0.007), cycling performance (2.5%, p = 0.003), and absolute VT (9 W, p = 0.005). However, only 57% of participants revealed meaningful increases in VO 2max and cycling performance in response to training, and two showed no change in either outcome. A greater volume of HIIT may be needed to maximize the training response for all individuals.

Branchial CO(2) receptors and cardiorespiratory adjustments during hypercarbia in Pacific spiny dogfish (Squalus acanthias).

PubMed

McKendry, J E; Milsom, W K; Perry, S F

2001-04-01

Adult Pacific spiny dogfish (Squalus acanthias) were exposed to acute (approximately 20 min) hypercarbia while we monitored arterial blood pressure, systemic vascular resistance (R(S)), cardiac output (V(b)) and frequency (fh) as well as ventilatory amplitude (V(AMP)) and frequency (f(V)). Separate series of experiments were conducted on control, atropinized (100 nmol kg(-1)) and branchially denervated fish to investigate putative CO(2)-chemoreceptive sites on the gills and their link to the autonomic nervous system and cardiorespiratory reflexes.In untreated fish, moderate hypercarbia (water CO(2 )partial pressure; Pw(CO2)=6.4+/-0.1 mmHg) (1 mmHg=0.133 kPa) elicited significant increases in V(AMP) (of approximately 92 %) and f(V) (of approximately 18 %) as well as decreases in fh (of approximately 64 %), V.(b) (approximately 29 %) and arterial blood pressure (of approximately 11 %); R(S) did not change significantly. Denervation of the branchial branches of cranial nerves IX and X to the pseudobranch and each gill arch eliminated all cardiorespiratory responses to hypercarbia. Prior administration of the muscarinic receptor antagonist atropine also abolished the hypercarbia-induced ventilatory responses and virtually eliminated all CO(2)-elicited cardiovascular adjustments. Although the atropinized dogfish displayed a hypercarbic bradycardia, the magnitude of the response was significantly attenuated (36+/-6 % decrease in fh in controls versus 9+/-2 % decrease in atropinized fish; means +/- s.e.m.).Thus, the results of the present study reveal the presence of gill CO(2) chemoreceptors in dogfish that are linked to numerous cardiorespiratory reflexes. In addition, because all cardiorespiratory responses to hypercarbia were abolished or attenuated by atropine, the CO(2) chemoreception process and/or one or more downstream elements probably involve cholinergic (muscarinic) neurotransmission.

The Effects of Elevated pCO2, Hypoxia and Temperature on Larval Sheepshead minnow, Cyprinodon variegatus: How much stress is too much?

EPA Science Inventory

Estuarine fish are acclimated to living in an environment with rapid and frequent changes in temperature, salinity, pH, and dissolved oxygen (DO) levels; the physiology of these organisms is well suited to cope with extreme thermal, hypercapnic, and hypoxic stress. While the adve...

Locomotory, ventilatory and metabolic responses of the subterranean Stenasellus virei (Crustacea, Isopoda) to severe hypoxia and subsequent recovery.

PubMed

Hervant, F; Mathieu, J; Messana, G

1997-02-01

The locomotory and ventilatory activities and the intermediary and energy metabolism modifications of the hypogean aquatic isopod crustacean Stenasellus virei were investigated in severe hypoxia (PO2 < 0.03 kPa) and subsequent recovery. The aims of this study were i) to determine why the subterranean species displayed a greater tolerance of hypoxia than numerous other epigean crustaceans, ii) to confirm previous results obtained with four hypogean and epigean crustaceans, iii) to compare the responses to severe hypoxia in hypogean amphipods and isopods, and iv) to better understand the ecological problems of the hypogean organisms survival in subterranean habitats. S. virei responded to experimental long-term, severe hypoxia with classical anaerobic metabolism mainly characterized by a decrease in adenosine triphosphate (ATP) and phosphagen, utilization of glycogen and glutamate, and accumulation of lactate and alanine. Lactate was also largely excreted by this organism, which is unusual for crustaceans in general. Compared to most other epigean crustaceans, the isopod S. virei showed high amounts of stored glycogen and arginine phosphate. These differences in glycogen and phosphagen stores, and the ability to reduce energetic expenditures linked to locomotion and ventilation, extended the survival of S. virei under experimental anaerobiosis. During recovery, the isopod S. virei showed a higher capacity for glyconeogenesis from lactate and a faster and total replenishment of ATP and arginine phosphate levels than epigean crustaceans. Data concerning responses to hypoxia and subsequent recovery in S. virei are similar to those previously obtained with two other hypogean amphipods, except that this isopod did not synthesize succinate in anaerobiosis.

A Randomized Clinical Trial Comparing the Effects of Antitussive Agents on Respiratory Center Output in Patients With Chronic Cough.

PubMed

Mannini, Claudia; Lavorini, Federico; Zanasi, Alessandro; Saibene, Federico; Lanata, Luigi; Fontana, Giovanni

2017-06-01

Cough is produced by the same neuronal pool implicated in respiratory rhythm generation, and antitussive drugs acting at the central level, such as opioids, may depress ventilation. Levodropropizine is classified as a nonopioid peripherally acting antitussive drug that acts at the level of airway sensory nerves. However, the lack of a central action by levodropropizine remains to be fully established. We set out to compare the effects of levodropropizine and the opioid antitussive agent dihydrocodeine on the respiratory responses to a conventional CO 2 rebreathing test in patients with chronic cough of any origin. Twenty-four outpatients (aged 39-70 years) with chronic cough were studied. On separate runs, each patient was randomly administered 60 mg levodropropizine, 15 mg dihydrocodeine, or a matching placebo. Subsequently, patients breathed a mixture of 93% oxygen and 7% CO 2 for 5 min. Fractional end-tidal CO 2 (Fetco 2 ) and inspiratory minute ventilation (V˙i) were continuously monitored. Changes in breathing pattern variables were also assessed. At variance with dihydrocodeine, levodropropizine and placebo did not affect respiratory responses to hypercapnia (P < .01). The ventilatory increases by hypercapnia were mainly accounted for by a rise in the volume components of the breathing pattern. The results are consistent with a peripheral action by levodropropizine; the assessment of ventilatory responses to CO 2 may represent a useful tool to investigate the central respiratory effects of antitussive agents. European Union Clinical Trials Register (EudraCT No.: 2013-004735-68); URL: https://www.clinicaltrialsregister.eu/. Copyright © 2017. Published by Elsevier Inc.

Hypoxic ventilatory response in Tac1-/- neonatal mice following exposure to opioids.

PubMed

Berner, J; Shvarev, Y; Zimmer, A; Wickstrom, R

2012-12-01

Morphine is the dominating analgetic drug used in neonates, but opioid-induced respiratory depression limits its therapeutic use. In this study, we examined acute morphine effects on respiration during intermittent hypoxia in newborn Tac1 gene knockout mice (Tac1-/-) lacking substance P and neurokinin A. In vivo, plethysmography revealed a blunted hypoxic ventilatory response (HVR) in Tac1-/- mice. Morphine (10 mg/kg) depressed the HVR in wild-type animals through an effect on respiratory frequency, whereas it increased tidal volumes in Tac1-/- during hypoxia, resulting in increased minute ventilation. Apneas were reduced during the first hypoxic episode in both morphine-exposed groups, but were restored subsequently in Tac1-/- mice. Morphine did not affect ventilation or apnea prevalence during baseline conditions. In vitro, morphine (50 nM) had no impact on anoxic response of brain stem preparations of either strain. In contrast, it suppressed the inspiratory rhythm during normoxia and potentiated development of posthypoxic neuronal arrest, especially in Tac1-/-. Thus this phenotype has a higher sensitivity to the depressive effects of morphine on inspiratory rhythm generation, but morphine does not modify the reactivity to oxygen deprivation. In conclusion, although Tac1-/- mice are similar to wild-type animals during normoxia, they differed by displaying a reversed pattern with an improved HVR during intermittent hypoxia both in vivo and in vitro. These data suggest that opioids and the substance P-ergic system interact in the HVR, and that reducing the activity in the tachykinin system may alter the respiratory effects of opioid treatment in newborns.

Ventilatory baroreflex sensitivity in humans is not modulated by chemoreflex activation

PubMed Central

Rivera, Eileen; Clarke, Debbie A.; Baugham, Ila L.; Ocon, Anthony J.; Taneja, Indu; Terilli, Courtney; Medow, Marvin S.

2011-01-01

Increasing arterial blood pressure (AP) decreases ventilation, whereas decreasing AP increases ventilation in experimental animals. To determine whether a “ventilatory baroreflex” exists in humans, we studied 12 healthy subjects aged 18–26 yr. Subjects underwent baroreflex unloading and reloading using intravenous bolus sodium nitroprusside (SNP) followed by phenylephrine (“Oxford maneuver”) during the following “gas conditions:” room air, hypoxia (10% oxygen)-eucapnia, and 30% oxygen-hypercapnia to 55–60 Torr. Mean AP (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), expiratory minute ventilation (VE), respiratory rate (RR), and tidal volume were measured. After achieving a stable baseline for gas conditions, we performed the Oxford maneuver. VE increased from 8.8 ± 1.3 l/min in room air to 14.6 ± 0.8 l/min during hypoxia and to 20.1 ± 2.4 l/min during hypercapnia, primarily by increasing tidal volume. VE doubled during SNP. CO increased from 4.9 ± .3 l/min in room air to 6.1 ± .6 l/min during hypoxia and 6.4 ± .4 l/min during hypercapnia with decreased TPR. HR increased for hypoxia and hypercapnia. Sigmoidal ventilatory baroreflex curves of VE versus MAP were prepared for each subject and each gas condition. Averaged curves for a given gas condition were obtained by averaging fits over all subjects. There were no significant differences in the average fitted slopes for different gas conditions, although the operating point varied with gas conditions. We conclude that rapid baroreflex unloading during the Oxford maneuver is a potent ventilatory stimulus in healthy volunteers. Tidal volume is primarily increased. Ventilatory baroreflex sensitivity is unaffected by chemoreflex activation, although the operating point is shifted with hypoxia and hypercapnia. PMID:21317304

Reduction of duration and cost of mechanical ventilation in an intensive care unit by use of a ventilatory management team.

PubMed

Cohen, I L; Bari, N; Strosberg, M A; Weinberg, P F; Wacksman, R M; Millstein, B H; Fein, I A

1991-10-01

To test the hypothesis that a formal interdisciplinary team approach to managing ICU patients requiring mechanical ventilation enhances ICU efficiency. Retrospective review with cost-effectiveness analysis. A 20-bed medical-surgical ICU in a 450-bed community referral teaching hospital with a critical care fellowship training program. All patients requiring mechanical ventilation in the ICU were included, comparing patients admitted 1 yr before the inception of the ventilatory management team (group 1) with those patients admitted for 1 yr after the inception of the team (group 2). Group 1 included 198 patients with 206 episodes of mechanical ventilation and group 2 included 165 patients with 183 episodes of mechanical ventilation. A team consisting of an ICU attending physician, nurse, and respiratory therapist was formed to conduct rounds regularly and supervise the ventilatory management of ICU patients who were referred to the critical care service. The two study groups were demographically comparable. However, there were significant reductions in resource use in group 2. The number of days on mechanical ventilation decreased (3.9 days per episode of mechanical ventilation [95% confidence interval 0.3 to 7.5 days]), as did days in the ICU (3.3 days per episode of mechanical ventilation [90% confidence interval 0.3 to 6.3 days]), numbers of arterial blood gases (23.2 per episode of mechanical ventilation; p less than .001), and number of indwelling arterial catheters (1 per episode of mechanical ventilation; p less than .001). The estimated cost savings from these reductions was $1,303 per episode of mechanical ventilation. We conclude that a ventilatory management team, or some component thereof, can significantly and safely expedite the process of "weaning" patients from mechanical ventilatory support in the ICU.

Pulmonary function test findings in patients with acute inhalation injury caused by smoke bombs

PubMed Central

Cao, Lu; Zhang, Xin-Gang; Wang, Jian-Guo; Wang, Han-Bin; Chen, Yi-Bing; Zhao, Da-Hui; Shi, Wen-Fang

2016-01-01

Background This study aimed to determine the effects of smoke bomb-induced acute inhalation injury on pulmonary function at different stages of lung injury. Methods We performed pulmonary function tests (PFTs) in 15 patients with acute inhalation injury from days 3 to 180 after smoke inhalation. We measured the trace element zinc in whole blood on days 4 and 17, and correlations of zinc levels with PFTs were performed. Results In the acute stage of lung injury (day 3), 3 of 11 patients with mild symptoms had normal pulmonary function and 8 patients with restrictive ventilatory dysfunction and reduced diffusing capacity. Some patients also had mild obstructive ventilatory dysfunction (5 patients) and a decline in small airway function (6 patients). For patients with severe symptoms, PFT results showed moderate to severe restrictive ventilatory dysfunction and reduced diffusing capacity. PaCO2 was significantly higher (P=0.047) in patients with reduced small airway function compared with those with normal small airway function. Whole blood zinc levels in the convalescence stage (day 17) were significantly lower than those in the acute stage (day 4). Zinc in the acute stage was negatively correlated with DLCO/VA on days 3, 10, and 46 (r=−0.633, −0.676, and −0.675 respectively, P<0.05). Conclusions Smoke inhalation injury mainly causes restrictive ventilatory dysfunction and reduced diffusing capacity, and causes mild obstructive ventilatory dysfunction and small airway function decline in some patients. Zinc is negatively correlated with DLCO/VA. Zinc levels may be able to predict prognosis and indicate the degree of lung injury. PMID:28066595

The effect of ventilatory muscle training on respiratory function and capacity in ambulatory and bed-ridden patients with neuromuscular disease.

PubMed

Gross, D; Meiner, Z

1993-08-01

Most patients with neuromuscular disease develop muscle weakness, including the ventilatory muscles leading to respiratory difficulty and, at times, respiratory insufficiency. We studied the effect of ventilatory muscle training on the ventilatory function and capacity of patients with various types of neuromuscular disease. The ambulatory patients were divided into three major groups. Group I (n = 6) patients with motor neuron disease (MND), such as amyotrophic latera sclerosis; Group II (n = 11) patients with myoneural junction disease (MNJ), such as myasthenia gravis and: Group III (n = 7) patients with muscle diseases such as progressive muscular disease. Patients were evaluated for their neuromuscular diagnosis and status of the disease. A complete physical examination and the various neuromuscular tests were performed. A complete respiratory evaluation was applied: pulmonary function tests (PFT), maximum inspiratory pressure (MIP). Patients then started ventilatory muscle training by resistive breathing, as a prophylactic treatment, for 10 min, three times daily, with a resistance which would induce fatigue. All tests were repeated every six weeks, and the results were as follow: forced vital capacity (FVC) changed from 38.8 +/- 12.3 to 53.2 +/- 9.6% (NS) of predicted value in group I, from 49.8 +/- 8.7 to 66.1 +/- 7.5% (p < 0.002) in group II, and from 47.0 +/- 7.5 to 53.3 +/- 7.6% (p < 0.04) in group III. Forced expiratory volume in one second (FEV1) was 34.8 +/- 11.0, 46.3 +/- 5, and 45.1 +/- 9% for the three groups, respectively, and did not change with training.(ABSTRACT TRUNCATED AT 250 WORDS)

The self-perception of dyspnoea threshold during the 6-min walk test: a good alternative to estimate the ventilatory threshold in chronic obstructive pulmonary disease.

PubMed

Couillard, Annabelle; Tremey, Emilie; Prefaut, Christian; Varray, Alain; Heraud, Nelly

2016-12-01

To determine and/or adjust exercise training intensity for patients when the cardiopulmonary exercise test is not accessible, the determination of dyspnoea threshold (defined as the onset of self-perceived breathing discomfort) during the 6-min walk test (6MWT) could be a good alternative. The aim of this study was to evaluate the feasibility and reproducibility of self-perceived dyspnoea threshold and to determine whether a useful equation to estimate ventilatory threshold from self-perceived dyspnoea threshold could be derived. A total of 82 patients were included and performed two 6MWTs, during which they raised a hand to signal self-perceived dyspnoea threshold. The reproducibility in terms of heart rate (HR) was analysed. On a subsample of patients (n=27), a stepwise regression analysis was carried out to obtain a predictive equation of HR at ventilatory threshold measured during a cardiopulmonary exercise test estimated from HR at self-perceived dyspnoea threshold, age and forced expiratory volume in 1 s. Overall, 80% of patients could identify self-perceived dyspnoea threshold during the 6MWT. Self-perceived dyspnoea threshold was reproducibly expressed in HR (coefficient of variation=2.8%). A stepwise regression analysis enabled estimation of HR at ventilatory threshold from HR at self-perceived dyspnoea threshold, age and forced expiratory volume in 1 s (adjusted r=0.79, r=0.63, and relative standard deviation=9.8 bpm). This study shows that a majority of patients with chronic obstructive pulmonary disease can identify a self-perceived dyspnoea threshold during the 6MWT. This HR at the dyspnoea threshold is highly reproducible and enable estimation of the HR at the ventilatory threshold.

Hypercarbic cardiorespiratory reflexes in the facultative air-breathing fish jeju (Hoplerythrinus unitaeniatus): the role of branchial CO2 chemoreceptors.

PubMed

de Lima Boijink, Cheila; Florindo, Luiz Henrique; Leite, Cleo A Costa; Kalinin, Ana Lúcia; Milsom, William K; Rantin, Francisco Tadeu

2010-08-15

The aim of the present study was to determine the roles that externally versus internally oriented CO(2)/H(+)-sensitive chemoreceptors might play in promoting cardiorespiratory responses to environmental hypercarbia in the air-breathing fish, Hoplerythrinus unitaeniatus (jeju). Fish were exposed to graded hypercarbia (1, 2.5, 5, 10 and 20% CO(2)) and also to graded levels of environmental acidosis (pH approximately 7.0, 6.0, 5.8, 5.6, 5.3 and 4.7) equal to the pH levels of the hypercarbic water to distinguish the relative roles of CO(2) versus H(+). We also injected boluses of CO(2)-equilibrated solutions (5, 10 and 20% CO(2)) and acid solutions equilibrated to the same pH as the CO(2) boluses into the caudal vein (internal) and buccal cavity (external) to distinguish between internal and external stimuli. The putative location of the chemoreceptors was determined by bilateral denervation of branches of cranial nerves IX (glossopharyngeal) and X (vagus) to the gills. The data indicate that the chemoreceptors eliciting bradycardia, hypertension and gill ventilatory responses (increased frequency and amplitude) to hypercarbia are exclusively branchial, externally oriented and respond specifically to changes in CO(2) and not H(+). Those involved in producing the cardiovascular responses appeared to be distributed across all gill arches while those involved in the gill ventilatory responses were located primarily on the first gill arch. Higher levels of aquatic CO(2) depressed gill ventilation and stimulated air breathing. The chemoreceptors involved in producing air breathing in response to hypercarbia also appeared to be branchial, distributed across all gill arches and responded specifically to changes in aquatic CO(2). This would suggest that chemoreceptor groups with different orientations (blood versus water) are involved in eliciting air-breathing responses to hypercarbia in jeju.

[The effect of tachykinins microinjections into the solitary tract nucleus on respiration and blood circulation in rats].

PubMed

Chepurnov, S A; Iniushkin, A N

1997-04-01

Administration of substance P and kassinin into the solitary tract nucleus of anesthetized rats induced a dose-dependent increase in ventilation, tidal volume, inspiratory muscle activity, and a decrease in the mean blood pressure and heart rate. Microinjections of peptides caused a decrease in ventilatory response to hypoxia and an inhibition of the Breuer-Hering reflex. The data obtained suggest involvement of tachykinins in the respiratory and circulatory control via the solitary tract nucleus.

Running economy and body composition between competitive and recreational level distance runners.

PubMed

Mooses, Martin; Jürimäe, J; Mäestu, J; Mooses, K; Purge, P; Jürimäe, T

2013-09-01

The aim of the present study was to compare running economy between competitive and recreational level athletes at their individual ventilatory thresholds on track and to compare body composition parameters that are related to the individual running economy measured on track. We performed a cross-sectional analysis of a total 45 male runners classified as competitive runners (CR; n = 28) and recreational runners (RR; n = 17). All runners performed an incremental test on treadmill until voluntary exhaustion and at least 48 h later a 2 × 2000 m test at indoor track with intensities according to ventilatory threshold 1, ventilator threshold 2. During the running tests, athletes wore portable oxygen analyzer. Body composition was measured with Dual energy X-ray absorptiometry (DXA) method. Running economy at the first ventilatory threshold was not significantly related to any of the measured body composition values or leg mass ratios either in the competitive or in the recreational runners group. This study showed that there was no difference in the running economy between distance runners with different performance level when running on track, while there was a difference in the second ventilatory threshold speed in different groups of distance runners. Differences in running economy between competitive and recreational athletes cannot be explained by body composition and/or different leg mass ratios.

Predictive value of ventilatory inflection points determined under field conditions.

PubMed

Heyde, Christian; Mahler, Hubert; Roecker, Kai; Gollhofer, Albert

2016-01-01

The aim of this study was to evaluate the predictive potential provided by two ventilatory inflection points (VIP1 and VIP2) examined in field without using gas analysis systems and uncomfortable facemasks. A calibrated respiratory inductance plethysmograph (RIP) and a computerised routine were utilised, respectively, to derive ventilation and to detect VIP1 and VIP2 during a standardised field ramp test on a 400 m running track on 81 participants. In addition, average running speed of a competitive 1000 m run (S1k) was observed as criterion. The predictive value of running speed at VIP1 (SVIP1) and the speed range between VIP1 and VIP2 in relation to VIP2 (VIPSPAN) was analysed via regression analysis. VIPSPAN rather than running speed at VIP2 (SVIP2) was operationalised as a predictor to consider the covariance between SVIP1 and SVIP2. SVIP1 and VIPSPAN, respectively, provided 58.9% and 22.9% of explained variance in regard to S1k. Considering covariance, the timing of two ventilatory inflection points provides predictive value in regard to a competitive 1000 m run. This is the first study to apply computerised detection of ventilatory inflection points in a field setting independent on measurements of the respiratory gas exchange and without using any facemasks.

Behavioral and autonomic thermoregulation in hamsters during microwave-induced heat exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gordon, C.J.; Long, M.D.; Fehlner, K.S.

1984-01-01

Preferred ambient temperature (Ta) and ventilatory frequency were measured in free-moving hamsters exposed to 2450-MHz microwaves. A waveguide exposure system that permits continuous monitoring of the absorbed heat load accrued from microwave exposure was imposed with a longitudinal temperature gradient which allowed hamsters to select their preferred Ta. Ventilatory frequency was monitored remotely by analysing the rhythmic shifts in unabsorbed microwave energy passing down the waveguide. Without microwave exposure hamsters selected an average T2 of 30.2 C. This preferred Ta did not change until the rate of heat absorption (SAR) from microwave exposure exceeded approx. 2 W kg-1. In amore » separate experiment, a SAR of 2.0 W kg-1 at a Ta of 30C was shown to promote an average 0.5 C increase in colonic temperature. Hamsters maintained their ventilatory frequency at baseline levels by selecting a cooler Ta during microwave exposure. These data support previous studies suggesting that during thermal stress behavioral thermo-regulation (i.e. preferred Ta) takes prescedence over autonomic thermoregulation (i.e. ventilatory frequency). It is apparent that selecting a cooler Ta is a more efficient and/or effective than autonomic thermoregulation for dissipating a heat load accrued from microwave exposure.« less

Effect of varying the pressurisation rate during noninvasive pressure support ventilation.

PubMed

Prinianakis, G; Delmastro, M; Carlucci, A; Ceriana, P; Nava, S

2004-02-01

The aim of the study was to assess the effects of varying the pressurisation rate during noninvasive pressure support ventilation on patients' breathing pattern, inspiratory effort, arterial blood gases, tolerance to ventilation and amount of air leakage. A total of 15 chronic obstructive pulmonary disease patients recovering from an acute episode of hypercapnic acute respiratory failure were studied during four randomised trials with different levels of pressurisation rate. No significant changes were observed in breathing pattern and arterial blood gases between the different runs. The pressure time product of the diaphragm, an estimate of its metabolic consumption, was significantly lower with all pressurisation rates than with spontaneous breathing, but was significantly lowest with the fastest rate. However, air leak, assessed by the ratio between expired and inspired tidal volumes, increased and the patients' tolerance of ventilation, measured using a standardised scale, was significantly poorer with the fastest pressurisation rate. In chronic obstructive pulmonary disease patients recovering from an episode of acute hypercapnic respiratory failure and ventilated with noninvasive pressure support ventilation, different pressurisation rates resulted in different reductions in the pressure time product of the diaphragm; this reduction was greater with the fastest rate, but was accompanied by significant air leaks and poor tolerance.

Arterial stiffness is associated with age-related differences in cerebrovascular conductance.

PubMed

Jaruchart, Tussana; Suwanwela, Nijasri C; Tanaka, Hirofumi; Suksom, Daroonwan

2016-01-01

To determine if arterial stiffness is associated with age-related differences in cerebrovascular conductance and reactivity, twenty-eight apparently healthy sedentary young (25±1 years; n=15) and older (67±1 years; n=13) adults were studied. Brachial-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. Cerebrovascular reactivity was determined by measuring changes in mean blood velocity in the middle cerebral artery under normocapnic, hypocapnic and hypercapnic conditions. Mean baPWV was greater (p<0.05) in older compared with young adults. At baseline, mean cerebral blood flow velocity and cerebrovascular conductance index were lower (p<0.05) in older compared with young adults under normocapnic, hypocapnic and hypercapnic conditions. There were no significant group differences in cerebrovascular reactivity when they were adjusted for stimuli (i.e., end-tidal CO2 concentrations) in most perturbation conditions except for the normocapnia to hypercapnia condition. baPWV was negatively associated with cerebrovascular conductance index at all conditions (all p<0.05). We concluded that arterial stiffness was associated with age-related differences in cerebrovascular conductance and that there were no apparent age-associated differences in cerebrovascular reactivity. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of Modes, Obesity, and Body Position on Non-invasive Positive Pressure Ventilation Success in the Intensive Care Unit: A Randomized Controlled Study.

PubMed

Türk, Murat; Aydoğdu, Müge; Gürsel, Gül

2018-01-01

Different outcomes and success rates of non-invasive positive pressure ventilation (NPPV) in patients with acute hypercapnic respiratory failure (AHRF) still pose a significant problem in intensive care units. Previous studies investigating different modes, body positioning, and obesity-associated hypoventilation in patients with chronic respiratory failure showed that these factors may affect ventilator mechanics to achieve a better minute ventilation. This study tried to compare pressure support (BiPAP-S) and average volume targeted pressure support (AVAPS-S) modes in patients with acute or acute-on-chronic hypercapnic respiratory failure. In addition, short-term effects of body position and obesity within both modes were analyzed. We conducted a randomized controlled study in a 7-bed intensive care unit. The course of blood gas analysis and differences in ventilation variables were compared between BiPAP-S (n=33) and AVAPS-S (n=29), and between semi-recumbent and lateral positions in both modes. No difference was found in the length of hospital stay and the course of PaCO2, pH, and HCO3 levels between the modes. There was a mean reduction of 5.7±4.1 mmHg in the PaCO2 levels in the AVAPS-S mode, and 2.7±2.3 mmHg in the BiPAP-S mode per session (p<0.05). Obesity didn't have any effect on the course of PaCO2 in both the modes. Body positioning had no notable effect in both modes. Although the decrease in the PaCO2 levels in the AVAPS-S mode per session was remarkably high, the course was similar in both modes. Furthermore, obesity and body positioning had no prominent effect on the PaCO2 response and ventilator mechanics. Post hoc power analysis showed that the sample size was not adequate to detect a significant difference between the modes.

Hypercapnia induced shifts in gill energy budgets of Antarctic notothenioids.

PubMed

Deigweiher, Katrin; Hirse, Timo; Bock, Christian; Lucassen, Magnus; Pörtner, Hans O

2010-03-01

Mechanisms responsive to hypercapnia (elevated CO(2) concentrations) and shaping branchial energy turnover were investigated in isolated perfused gills of two Antarctic Notothenioids (Gobionotothen gibberifrons, Notothenia coriiceps). Branchial oxygen consumption was measured under normo- versus hypercapnic conditions (10,000 ppm CO(2)) at high extracellular pH values. The fractional costs of ion regulation, protein and RNA synthesis in the energy budgets were determined using specific inhibitors. Overall gill energy turnover was maintained under pH compensated hypercapnia in both Antarctic species as well as in a temperate zoarcid (Zoarces viviparus). However, fractional energy consumption by the examined processes rose drastically in G. gibberifrons (100-180%), and to a lesser extent in N. coriiceps gills (7-56%). In conclusion, high CO(2) concentrations under conditions of compensated acidosis induce cost increments in epithelial processes, however, at maintained overall rates of branchial energy turnover.

Effect of Six Days of Staging on Physiologic Adjustments and Acute Mountain Sickness During Ascent to 4300 Meters

DTIC Science & Technology

2009-01-01

respiratory alkalosis due to hyperventilation that was partially compensated for by increased excretion of HCO3 to maintain a normal pH following...carbon dioxide; RER, respiratory exchange quotient; Sao2, arterial oxygen saturation; Paco2, partial pressure of capillary-arterialized carbon dioxide...dioxide production; E=O2, ventilatory equivalent for oxygen; E=CO2, ventilatory equivalent for carbon dioxide; RER, respiratory exchange quotient

Clinical review: Long-term noninvasive ventilation

PubMed Central

Robert, Dominique; Argaud, Laurent

2007-01-01

Noninvasive positive ventilation has undergone a remarkable evolution over the past decades and is assuming an important role in the management of both acute and chronic respiratory failure. Long-term ventilatory support should be considered a standard of care to treat selected patients following an intensive care unit (ICU) stay. In this setting, appropriate use of noninvasive ventilation can be expected to improve patient outcomes, reduce ICU admission, enhance patient comfort, and increase the efficiency of health care resource utilization. Current literature indicates that noninvasive ventilation improves and stabilizes the clinical course of many patients with chronic ventilatory failure. Noninvasive ventilation also permits long-term mechanical ventilation to be an acceptable option for patients who otherwise would not have been treated if tracheostomy were the only alternative. Nevertheless, these results appear to be better in patients with neuromuscular/-parietal disorders than in chronic obstructive pulmonary disease. This clinical review will address the use of noninvasive ventilation (not including continuous positive airway pressure) mainly in diseases responsible for chronic hypoventilation (that is, restrictive disorders, including neuromuscular disease and lung disease) and incidentally in others such as obstructive sleep apnea or problems of central drive. PMID:17419882

Behavioral characterization of the alarm reaction and anxiolytic-like effect of acute treatment with fluoxetine in piauçu fish.

PubMed

Barbosa Júnior, Augusto; Alves, Fabiana Luca; Pereira, Aparecida de Sousa Fim; Ide, Liliam Midori; Hoffmann, Anette

2012-02-01

In Ostariophysan fish, the detection of the alarm substance liberated into the water as a consequence of an attack by a predator elicits an alarm reaction or anti-predatory behavior. In this study, experiments were performed to: (i) describe and quantitatively characterize the behavioral and ventilatory responses in piauçu fish (Leporinus macrocephalus), individually and as part of a school, to conspecific alarm substance (CAS) and; (ii) test the effect of acute fluoxetine treatment on alarm reaction. Histological analysis revealed the presence of club cells in the intermediate and superficial layers of the epidermis. The predominant behavioral response to CAS was freezing for fish held individually, characterized by the cessation of the swimming activity as the animal settles to a bottom corner of the aquarium. Fish exposed to CAS showed decrease in the mean ventilatory frequency (approximately 13%) relative to control. In schools, CAS elicited a biphasic response that was characterized by erratic movements followed by increased school cohesion and immobility, reflected as an increased school cohesion (65.5% vs. -5.8% for controls) and in the number of animals near the bottom of the aquarium (42.0% vs. 6.5% for controls). Animals treated with single i.p. injections of fluoxetine (10 μg/g b.w.) did not exhibit alarm behavior following CAS stimulation. These results show that an alarm pheromone system is present in piauçu fish, evidenced by the presence of epidermal club cells and an alarm reaction induced by CAS and consequently of a chemosensory system to transmit the appropriate information to neural structures responsible for initiating anti-predator behavioral responses. In addition, fluoxetine treatment caused an anxiolytic-like effect following CAS exposure. Thus, the alarm reaction in piauçu can be a useful model for neuroethological and pharmacological studies of anxiety-related states. Copyright © 2011 Elsevier Inc. All rights reserved.

Impact of genetic strain on body fat loss, food consumption, metabolism, ventilation, and motor activity in free running female rats.

PubMed

Gordon, C J; Phillips, P M; Johnstone, A F M

2016-01-01

Chronic exercise is considered as one of the most effective means of countering symptoms of the metabolic syndrome (MS) such as obesity and hyperglycemia. Rodent models of forced or voluntary exercise are often used to study the mechanisms of MS and type 2 diabetes. However, there is little known on the impact of genetic strain on the metabolic response to exercise. We studied the effects of housing rats with running wheels (RW) for 65 days compared to sedentary (SED) housing in five female rat strains: Sprague-Dawley (SD), Long-Evans (LE), Wistar (WIS), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY). Key parameters measured were total distance run, body composition, food consumption, motor activity, ventilatory responses by plethysmography, and resting metabolic rate (MR). WKY and SHR ran significantly more than the WIS, LE, and SD strains. Running-induced reduction in body fat was affected by strain but not by distance run. LE's lost 6% fat after 21 d of running whereas WKY's lost 2% fat but ran 40% more than LE's. LE and WIS lost body weight while the SHR and WKY strains gained weight during running. Food intake with RW was markedly increased in SHR, WIS, and WKY while LE and SD showed modest increases. Exploratory motor activity was reduced sharply by RW in all but the SD strain. Ventilatory parameters were primarily altered by RW in the SHR, WKY, and WIS strains. MR was unaffected by RW. In an overall ranking of physiological and behavioral responses to RW, the SD strain was considered the least responsive whereas the WIS was scored as most responsive. In terms of RW-induced fat loss, the LE strain appears to be the most ideal. These results should be useful in the future selection of rat models to study benefits of volitional exercise. Published by Elsevier Inc.

Sleep-induced periodic breathing and apnea: a theoretical study.

PubMed

Khoo, M C; Gottschalk, A; Pack, A I

1991-05-01

To elucidate the mechanisms that lead to sleep-disordered breathing, we have developed a mathematical model that allows for dynamic interactions among the chemical control of respiration, changes in sleep-waking state, and changes in upper airway patency. The increase in steady-state arterial PCO2 accompanying sleep is shown to be inversely related to the ventilatory response to CO2. Chemical control of respiration becomes less stable during the light stage of sleep, despite a reduction in chemoresponsiveness, due to a concomitant increase in "plant gain" (i.e., responsiveness of blood gases to ventilatory changes). The withdrawal of the "wakefulness drive" during sleep onset represents a strong perturbation to respiratory control: higher magnitudes and rates of withdrawal of this drive favor instability. These results may account for the higher incidence of periodic breathing observed during light sleep and sleep onset. Periodic ventilation can also result from repetitive alternations between sleep onset and arousal. The potential for instability is further compounded if the possibility of upper airway occlusion is also included. In systems with high controller gains, instability is mediated primarily through chemoreflex overcompensation. However, in systems with depressed chemoresponsiveness, rapid sleep onset and large blood gas fluctuations trigger repetitive episodes of arousal and hyperpnea alternating with apneas that may or may not be obstructive. Between these extremes, more complex patterns can arise from the interaction between chemoreflex-mediated oscillations of shorter-cycle-duration (approximately 36 s) and longer-wavelength (approximately 60-80 s) state-driven oscillations.

Ventilatory Cycle Measurements and Loop Gain in Central Apnea in Mining Drivers Exposed to Intermittent Altitude

PubMed Central

Rey de Castro, Jorge; Liendo, Alicia; Ortiz, Oswaldo; Rosales-Mayor, Edmundo; Liendo, César

2017-01-01

Study Objectives: By measuring the apnea length, ventilatory phase, respiratory cycle length, and loop gain, we can further characterize the central apneas of high altitude (CAHA). Methods: Sixty-three drivers of all-terrain vehicles, working in a Peruvian mine located at 2,020 meters above sea level (MASL), were evaluated. A respiratory polygraph was performed in the first night they slept at high altitude. None of the subjects were exposed to oxygen during the test or acetazolamide in the preceding days of the test. Results: Sixty-three respiratory polygraphs were performed, and 59 were considered for analysis. Forty-six (78%) were normal, 6 (10%) had OSA, and 7 (12%) had CAHA. Key data from subjects include: residing altitude: 341 ± 828 MASL, Lake Louise scoring: 0.4 ± 0.8, Epworth score: 3.4 ± 2.7, apneahypopnea index: 35.7 ± 19.3, CA index: 13.4 ± 14.2, CA length: 14.4 ± 3.6 sec, ventilatory length: 13.5 ± 2.9 sec, cycle length: 26.5 ± 4.0 sec, ventilatory length/CA length ratio 0.9 ± 0.3 and circulatory delay 13.3 ± 2.9 sec. Duty ratio media [ventilatory duration/cycle duration] was 0.522 ± 0 0.128 [0.308–0.700] and loop gain was calculated from the duty ratio utilizing this formula: LG = 2π / [(2πDR-sin(2πDR)]. All subjects have a high loop gain media 2.415 ± 1.761 [1.175–6.260]. Multiple correlations were established with loop gain values, but the only significant correlation detected was between central apnea index and loop gain. Conclusions: Twelve percent of the studied population had CAHA. Measurements of respiratory cycle in workers with CAHA are more similar to idiopathic central apneas rather than Hunter-Cheyne-Stokes respiration. Also, there was a high degree of correlation between severity of central apnea and the degree of loop gain. The abnormal breathing patterns in those subjects could affect the sleep quality and potentially increase the risk for work accidents. Citation: Rey de Castro J, Liendo A, Ortiz O, Rosales-Mayor E, Liendo C. Ventilatory cycle measurements and loop gain in central apnea in mining drivers exposed to intermittent altitude. J Clin Sleep Med. 2017;13(1):27–32. PMID:27707449

Carbon dioxide induces erratic respiratory responses in bipolar disorder.

PubMed

Mackinnon, Dean F; Craighead, Brandie; Lorenz, Laura

2009-01-01

CO(2) respiration stimulates both anxiety and dyspnea ("air hunger") and has long been used to study panic vulnerability and respiratory control. High comorbidity with panic attacks suggests individuals with bipolar disorder may also mount a heightened anxiety response to CO(2). Moreover, problems in the arousal and modulation of appetites are central to the clinical syndromes of mania and depression; hence CO(2) may arouse an abnormal respiratory response to "air hunger". 72 individuals (34 bipolar I, 25 depressive and bipolar spectrum, 13 with no major affective diagnosis) breathed air and air with 5% CO(2) via facemask for up to 15 min each; subjective and respiratory responses were recorded. Nearly half the subjects diverged from the typical response to a fixed, mildly hypercapneic environment, which is to increase breathing acutely, and then maintain a hyperpneic plateau. The best predictors of an abnormal pattern were bipolar diagnosis and anxiety from air alone. 25 individuals had a panic response; panic responses from CO(2) were more likely in subjects with bipolar I compared to other subjects, however the best predictors of a panic response overall were anxiety from air alone and prior history of panic attacks. Heterogeneous sample, liberal definition of panic attack. Carbon dioxide produces abnormal respiratory and heightened anxiety responses among individuals with bipolar and depressive disorders. These may be due to deficits in emotional conditioning related to fear and appetite. Although preliminary, this work suggests a potentially useful test of a specific functional deficit in bipolar disorder.

Respiratory failure due to tracheobronchomalacia.

PubMed Central

Collard, P.; Freitag, L.; Reynaert, M. S.; Rodenstein, D. O.; Francis, C.

1996-01-01

A case is described of tracheobronchomegaly progressing to extensive tracheomalacia, complicated by episodic choking, recurrent pulmonary infections, and irreversible hypercapnic respiratory failure. A Y-shaped tracheobronchial stent was placed endoscopically to splint the trachea open, with excellent clinical and physiological improvement. New stent designs may provide long term palliation in selected cases of diffuse tracheal collapse or stenosis, and offer an alternative to surgical repair. PMID:8711665

Cardiac arrhythmias from a malpositioned Greenfield filter in a traumatic quadriplegic.

PubMed

Bach, J R; Zaneuski, R; Lee, H

1990-10-01

A case study is presented of premature Greenfield filter discharge with intracardiac migration and resulting life-threatening arrhythmias. These arrhythmias also interfered with the patient's transition from ventilatory support via orotracheal intubation to noninvasive positive airway pressure ventilatory support methods. The patient's arrhythmias were controlled by a demand cardiac pacemaker and cardiac glycoside therapy. No anticoagulants were used. She had no further filter migration nor significant complications for 16 months after hospital discharge.

Relationships (II) of International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases with ventilatory functions indices for parenchymal abnormalities.

PubMed

Tamura, Taro; Suganuma, Narufumi; Hering, Kurt G; Vehmas, Tapio; Itoh, Harumi; Akira, Masanori; Takashima, Yoshihiro; Hirano, Harukazu; Kusaka, Yukinori

2015-01-01

The International Classification of High-Resolution Computed Tomography (HRCT) for Occupational and Environmental Respiratory Diseases (ICOERD) is used to screen and diagnose respiratory illnesses. Using univariate and multivariate analysis, we investigated the relationship between subject characteristics and parenchymal abnormalities according to ICOERD, and the results of ventilatory function tests (VFT). Thirty-five patients with and 27 controls without mineral-dust exposure underwent VFT and HRCT. We recorded all subjects' occupational history for mineral dust exposure and smoking history. Experts independently assessed HRCT using the ICOERD parenchymal abnormalities (Items) grades for well-defined rounded opacities (RO), linear and/or irregular opacities (IR), and emphysema (EM). High-resolution computed tomography showed that 11 patients had RO; 15 patients, IR; and 19 patients, EM. According to the multiple regression model, age and height had significant associations with many indices ventilatory functions such as vital capacity, forced vital capacity, and forced expiratory volume in 1 s (FEV1). The EM summed grades on the upper, middle, and lower zones of the right and left lungs also had significant associations with FEV1 and the maximum mid-expiratory flow rate. The results suggest the ICOERD notation is adequate based on the good and significant multiple regression modeling of ventilatory function with the EM summed grades.

The 6-minute walk test in chronic respiratory failure: does observed or predicted walk distance better reflect patient functional status?

PubMed

Güngör, Gökay; Karakurt, Zuhal; Adigüzel, Nalan; Aydin, Rüya Evin; Balci, Merih Kalamanoğlu; Saltürk, Cüneyt; Sancar, Raziye; Solmaz, Suat; Moçin, Özlem Yazicioğlu

2013-05-01

Acquiring 6-min walk test (6MWT) data from patients undergoing noninvasive mechanical ventilation due to chronic hypercapnic respiratory failure is limited. We aimed to assess whether the actual 6-min walk distance (6MWD) or the percent predicted 6MWD is a better reflection of the respiratory function of patients using home noninvasive ventilation (NIV) due to chronic hypercapnic respiratory failure. This was a cross-sectional observational study. The 6MWT was performed in subjects using home NIV. Diagnoses were grouped as COPD, obesity hypoventilation syndrome (OHS), kyphoscoliosis, and parenchymal lung disease. Sex, age, and body mass index (BMI) were used to calculate ideal 6MWD. Male: 1,140 m - (5.61 × BMI) - (6.94 × age), and subtract 153 m for the lower limit of normal. Female: 1,017 m - (6.24 × BMI) - (5.83 × age), and subtract 139 m for the lower limit of normal. The 6MWD and percent-of-predicted 6MWD were compared relative to arterial blood gas, spirometry values, and diagnosis. The 6MWT was performed in 144 subjects, median (IQR) age 62 y (55-71 y). The male/female ratio, median (IQR) 6MWD, and percent-of-predicted 6MWD values were: COPD 32/6, 316 m (226-390 m), and 59.4% (42.5-68.9%); OHS 24/28, 303 m (240-362 m), and 73.0% (63.0-82.0%); kyphoscoliosis 16/7, 420 m (318-462 m), and 70.5% (56.0-75.2%); and parenchymal lung disease 19/12, 333 m (273-372 m), and 67.1% (46.7-74.7%). The correlation of percent-of-predicted 6MWD with spirometry and arterial blood gas values were better than with the actual 6MWD. The percent-of-predicted 6MWD was better correlated with respiratory function than actual 6MWD for subjects using home NIV due to chronic hypercapnic respiratory failure with COPD, OHS, kyphoscoliosis, and parenchymal lung disease.

Altitude matters: differences in cardiovascular and respiratory responses to hypoxia in bar-headed geese reared at high and low altitudes.

PubMed

Lague, Sabine L; Chua, Beverly; Farrell, Anthony P; Wang, Yuxiang; Milsom, William K

2016-07-01

Bar-headed geese (Anser indicus) fly at high altitudes during their migration across the Himalayas and Tibetan plateau. However, we know relatively little about whether rearing at high altitude (i.e. phenotypic plasticity) facilitates this impressive feat because most of what is known about their physiology comes from studies performed at sea level. To provide this information, a comprehensive analysis of metabolic, cardiovascular and ventilatory responses to progressive decreases in the equivalent fractional composition of inspired oxygen (FiO2 : 0.21, 0.12, 0.09, 0.07 and 0.05) was made on bar-headed geese reared at either high altitude (3200 m) or low altitude (0 m) and on barnacle geese (Branta leucopsis), a low-altitude migrating species, reared at low altitude (0 m). Bar-headed geese reared at high altitude exhibited lower metabolic rates and a modestly increased hypoxic ventilatory response compared with low-altitude-reared bar-headed geese. Although the in vivo oxygen equilibrium curves and blood-oxygen carrying capacity did not differ between the two bar-headed goose study groups, the blood-oxygen carrying capacity was higher than that of barnacle geese. Resting cardiac output also did not differ between groups and increased at least twofold during progressive hypoxia, initially as a result of increases in stroke volume. However, cardiac output increased at a higher FiO2  threshold in bar-headed geese raised at high altitude. Thus, bar-headed geese reared at high altitude exhibited a reduced oxygen demand at rest and a modest but significant increase in oxygen uptake and delivery during progressive hypoxia compared with bar-headed geese reared at low altitude. © 2016. Published by The Company of Biologists Ltd.

Hyperadditive Ventilatory Response Arising from Interaction between the Carotid Chemoreflex and the Muscle Mechanoreflex in Healthy Humans.

PubMed

Silva, Talita M; Aranda, Liliane C; Paula-Ribeiro, Marcelle; Oliveira, Diogo M; Medeiros, Wladimir Musetti; Vianna, Lauro C; Nery, Luiz E; Silva, Bruno M

2018-03-22

Physical exercise potentiates the carotid chemoreflex control of ventilation (VE). Hyperadditive neural interactions may partially mediate the potentiation. However, some neural interactions remain incompletely explored. As the potentiation occurs even during low-intensity exercise, we tested the hypothesis that the carotid chemoreflex and the muscle mechanoreflex could interact in a hyperadditive fashion. Fourteen young healthy subjects inhaled, randomly, in separate visits, 12% O 2 to stimulate the carotid chemoreflex, and 21% O 2 as control. A rebreathing circuit maintained isocapnia. During gases administration, subjects either remained at rest (i.e., normoxic and hypoxic rest) or the muscle mechanoreflex was stimulated, via passive knee movement (i.e., normoxic and hypoxic movement). Surface muscle electrical activity did not increase during the passive movement, confirming the absence of active contractions. Hypoxic rest and normoxic movement similarly increased VE [change (mean {plus minus} SEM) = 1.24 {plus minus} 0.72 vs. 0.73 {plus minus} 0.43 L/min, respectively; P = 0.46], but hypoxic rest only increased tidal volume (Vt) and normoxic movement only increased breathing frequency (BF). Hypoxic movement induced greater VE and mean inspiratory flow (Vt/Ti) increase than the sum of hypoxic rest and normoxic movement isolated responses (VE change: hypoxic movement = 3.72 {plus minus} 0.81 vs. sum = 1.96 {plus minus} 0.83 L/min, P = 0.01; Vt/Ti change: hypoxic movement = 0.13 {plus minus} 0.03 vs. sum = 0.06 {plus minus} 0.03 L/s, P = 0.02). Moreover, hypoxic movement increased both Vt and BF. Collectively, the results indicate the carotid chemoreflex and the muscle mechanoreflex interacted mediating a hyperadditive ventilatory response in healthy humans.

Cardiorespiratory Coupling: Common Rhythms in Cardiac, Sympathetic, and Respiratory Activities

PubMed Central

Dick, Thomas E.; Hsieh, Yee-Hsee; Dhingra, Rishi R.; Baekey, David M.; Galán, Roberto F.; Wehrwein, Erica; Morris, Kendall F.

2014-01-01

Cardiorespiratory coupling is an encompassing term describing more than the well-recognized influences of respiration on heart rate and blood pressure. Our data indicate that cardiorespiratory coupling reflects a reciprocal interaction between autonomic and respiratory control systems, and the cardiovascular system modulates the ventilatory pattern as well. For example, cardioventilatory coupling refers to the influence of heart beats and arterial pulse pressure on respiration and is the tendency for the next inspiration to start at a preferred latency after the last heart beat in expiration. Multiple complementary, well-described mechanisms mediate respiration’s influence on cardiovascular function, whereas mechanisms mediating the cardiovascular system’s influence on respiration may only be through the baroreceptors but are just being identified. Our review will describe a differential effect of conditioning rats with either chronic intermittent or sustained hypoxia on sympathetic nerve activity but also on ventilatory pattern variability. Both intermittent and sustained hypoxia increase sympathetic nerve activity after 2 weeks but affect sympatho-respiratory coupling differentially. Intermittent hypoxia enhances sympatho-respiratory coupling, which is associated with low variability in the ventilatory pattern. In contrast, after constant hypobaric hypoxia, 1-to-1 coupling between bursts of sympathetic and phrenic nerve activity is replaced by 2-to-3 coupling. This change in coupling pattern is associated with increased variability of the ventilatory pattern. After baro-denervating hypobaric hypoxic-conditioned rats, splanchnic sympathetic nerve activity becomes tonic (distinct bursts are absent) with decreases during phrenic nerve bursts and ventilatory pattern becomes regular. Thus, conditioning rats to either intermittent or sustained hypoxia accentuates the reciprocal nature of cardiorespiratory coupling. Finally, identifying a compelling physiologic purpose for cardiorespiratory coupling is the biggest barrier for recognizing its significance. Cardiorespiratory coupling has only a small effect on the efficiency of gas exchange; rather, we propose that cardiorespiratory control system may act as weakly coupled oscillator to maintain rhythms within a bounded variability. PMID:24746049

Effect of CO₂ on the ventilatory sensitivity to rising body temperature during exercise.

PubMed

Hayashi, Keiji; Honda, Yasushi; Miyakawa, Natsuki; Fujii, Naoto; Ichinose, Masashi; Koga, Shunsaku; Kondo, Narihiko; Nishiyasu, Takeshi

2011-05-01

We examined the degree to which ventilatory sensitivity to rising body temperature (the slope of the regression line relating ventilation and body temperature) is altered by restoration of arterial PCO(2) to the eucapnic level during prolonged exercise in the heat. Thirteen subjects exercised for ~60 min on a cycle ergometer at 50% of peak O(2) uptake with and without inhalation of CO(2)-enriched air. Subjects began breathing CO(2)-enriched air at the point that end-tidal Pco(2) started to decline. Esophageal temperature (T(es)), minute ventilation (V(E)), tidal volume (V(T)), respiratory frequency (f(R)), respiratory gases, middle cerebral artery blood velocity, and arterial blood pressure were recorded continuously. When V(E), V(T), f(R), and ventilatory equivalents for O(2) uptake (V(E)/VO(2)) and CO(2) output (V(E)/VCO(2)) were plotted against changes in T(es) from the start of the CO(2)-enriched air inhalation (ΔT(es)), the slopes of the regression lines relating V(E), V(T), V(E)/VO(2), and V(E)/VCO(2) to ΔT(es) (ventilatory sensitivity to rising body temperature) were significantly greater when subjects breathed CO(2)-enriched air than when they breathed room air (V(E): 19.8 ± 10.3 vs. 8.9 ± 6.7 l·min(-1)·°C(-1), V(T): 18 ± 120 vs. -81 ± 92 ml/°C; V(E)/VO(2): 7.4 ± 5.5 vs. 2.6 ± 2.3 units/°C, and V(E)/VCO(2): 7.6 ± 6.6 vs. 3.4 ± 2.8 units/°C). The increase in Ve was accompanied by increases in V(T) and f(R). These results suggest that restoration of arterial PCO(2) to nearly eucapnic levels increases ventilatory sensitivity to rising body temperature by around threefold.

The influence of weight loss on anaerobic threshold in obese women.

PubMed

Zak-Golab, Agnieszka; Zahorska-Markiewicz, Barbara; Langfort, Józef; Kocelak, Piotr; Holecki, Michal; Mizia-Stec, Katarzyna; Olszanecka-Glinianowicz, Magdalena; Chudek, Jerzy

2010-01-01

Obesity is associated with decreased physical activity. The aim of the study was to assess the anaerobic threshold in obese and normal weight women and to analyse the effect of weight-reduction therapy on the determined thresholds. 42 obese women without concomitant disease (age 30.5 ± 6.9y; BMI 33.6 ± 3.7 kg·m(-2)) and 19 healthy normal weight women (age 27.6 ± 7.0y; BMI 21.2 ± 1.9 kg·m(-2)) performed cycle ergometer incremental ramp exercise test up to exhaustion. The test was repeated in 19 obese women after 12.3 ± 4.2% weight loss. The lactate threshold (LT) and the ventilatory threshold (VT) were determined. Obese women had higher lactate (expressed as oxygen consumption) and ventilator threshold than normal weight women. The lactate threshold was higher than ventilatory one both in obese and normal weight women (1.11 ± 0.21 vs 0.88 ± 0.18 L·min(-1), p < 0.001; 0.94 ± 0.15 vs 0.79 ± 0.23 L·min(- 1), p < 0.01, respectively). After weight reduction therapy neither the lactate nor the ventilatory threshold changed significantly. The results concluded that; 1. The higher lactate threshold noted in obese women may be related to the increased fat acid usage in metabolism. 2. Both in obese and normal weight women lactate threshold appears at higher oxygen consumption than ventilatory threshold. 3. The obtained weight reduction, without weight normalisation was insufficient to cause significant changes of lactate and ventilatory thresholds in obese women. Key pointsResults showed that adolescent young female gymnasts have an altered serum inflammatory markers and endothelial activation, compared to their less physically active peers.Physical activities improved immune system.Differences in these biochemical data kept significant after adjustment for body weight and height.

Assessment of ventilatory thresholds during graded and maximal exercise test using time varying analysis of respiratory sinus arrhythmia.

PubMed

Blain, G; Meste, O; Bouchard, T; Bermon, S

2005-07-01

To test whether ventilatory thresholds, measured during an exercise test, could be assessed using time varying analysis of respiratory sinus arrhythmia frequency (f(RSA)). Fourteen sedentary subjects and 12 endurance athletes performed a graded and maximal exercise test on a cycle ergometer: initial load 75 W (sedentary subjects) and 150 W (athletes), increments 37.5 W/2 min. f(RSA) was extracted from heart period series using an evolutive model. First (T(V1)) and second (T(V2)) ventilatory thresholds were determined from the time course curves of ventilation and ventilatory equivalents for O(2) and CO(2). f(RSA) was accurately extracted from all recordings and positively correlated to respiratory frequency (r = 0.96 (0.03), p<0.01). In 21 of the 26 subjects, two successive non-linear increases were determined in f(RSA), defining the first (T(RSA1)) and second (T(RSA2)) f(RSA) thresholds. When expressed as a function of power, T(RSA1) and T(RSA2) were not significantly different from and closely linked to T(V1) (r = 0.99, p<0.001) and T(V2) (r = 0.99, p<0.001), respectively. In the five remaining subjects, only one non-linear increase was observed close to T(V2). Significant differences (p<0.04) were found between athlete and sedentary groups when T(RSA1) and T(RSA2) were expressed in terms of absolute and relative power and percentage of maximal aerobic power. In the sedentary group, T(RSA1) and T(RSA2) were 150.3 (18.7) W and 198.3 (28.8) W, respectively, whereas in the athlete group T(RSA1) and T(RSA2) were 247.3 (32.8) W and 316.0 (28.8) W, respectively. Dynamic analysis of f(RSA) provides a useful tool for identifying ventilatory thresholds during graded and maximal exercise test in sedentary subjects and athletes.

Assessment of ventilatory thresholds during graded and maximal exercise test using time varying analysis of respiratory sinus arrhythmia

PubMed Central

Blain, G; Meste, O; Bouchard, T; Bermon, S; Segura, R.

2005-01-01

Objective: To test whether ventilatory thresholds, measured during an exercise test, could be assessed using time varying analysis of respiratory sinus arrhythmia frequency (fRSA). Methods: Fourteen sedentary subjects and 12 endurance athletes performed a graded and maximal exercise test on a cycle ergometer: initial load 75 W (sedentary subjects) and 150 W (athletes), increments 37.5 W/2 min. fRSA was extracted from heart period series using an evolutive model. First (TV1) and second (TV2) ventilatory thresholds were determined from the time course curves of ventilation and ventilatory equivalents for O2 and CO2. Results: fRSA was accurately extracted from all recordings and positively correlated to respiratory frequency (r = 0.96 (0.03), p<0.01). In 21 of the 26 subjects, two successive non-linear increases were determined in fRSA, defining the first (TRSA1) and second (TRSA2) fRSA thresholds. When expressed as a function of power, TRSA1 and TRSA2 were not significantly different from and closely linked to TV1 (r = 0.99, p<0.001) and TV2 (r = 0.99, p<0.001), respectively. In the five remaining subjects, only one non-linear increase was observed close to TV2. Significant differences (p<0.04) were found between athlete and sedentary groups when TRSA1 and TRSA2 were expressed in terms of absolute and relative power and percentage of maximal aerobic power. In the sedentary group, TRSA1 and TRSA2 were 150.3 (18.7) W and 198.3 (28.8) W, respectively, whereas in the athlete group TRSA1 and TRSA2 were 247.3 (32.8) W and 316.0 (28.8) W, respectively. Conclusions: Dynamic analysis of fRSA provides a useful tool for identifying ventilatory thresholds during graded and maximal exercise test in sedentary subjects and athletes. PMID:15976169

Assessment of two novel ventilatory surrogates for use in the delivery of gated/tracked radiotherapy for non-small cell lung cancer.

PubMed

Hughes, Simon; McClelland, James; Tarte, Segolene; Lawrence, David; Ahmad, Shahreen; Hawkes, David; Landau, David

2009-06-01

In selected patients with NSCLC the therapeutic index of radical radiotherapy can be improved with gating/tracking technology. Both techniques require real-time information on target location. This is often derived from a surrogate ventilatory signal. We assessed the correlation of two novel surrogate ventilatory signals with a spirometer-derived signal. The novel signals were obtained using the VisionRT stereoscopic camera system. The VisionRT-Tracked-Point (VRT-TP) signal was derived from tracking a point located midway between the umbilicus and xiphisternum. The VisionRT-Surface-Derived-Volume (VRT-SDV) signal was derived from 3D body surface imaging of the torso. Both have potential advantages over the current surrogate signals. Eleven subjects with NSCLC were recruited. Each was positioned as for radiotherapy treatment, and then instructed to breathe in five different modes: normal, abdominal, thoracic, deep and shallow breathing. Synchronous ventilatory signals were recorded for later analysis. The signals were analysed for correlation across all modes of breathing, and phase shifts. The VRT-SDV was also assessed for its ability to determine the mode of breathing. Both novel respiratory signals showed good correlation (r>0.80) with spirometry in 9 of 11 subjects. For all subjects the correlation with spirometry was better for the VRT-SDV signal than for the VRT-TP signal. Only one subject displayed a phase shift between the VisionRT-derived signals and spirometry. The VRT-SDV signal could also differentiate between different modes of breathing. Unlike the spirometer-derived signal, neither VisionRT-derived signal was subject to drift. Both the VRT-TP and VRT-SDV signals have potential applications in ventilatory-gated and tracked radiotherapy. They can also be used as a signal for sorting 4DCT images, and to drive 4DCT single- and multiple-parameter motion models.

Imagery use and affective responses during exercise: an examination of cerebral hemodynamics using near-infrared spectroscopy.

PubMed

Tempest, Gavin; Parfitt, Gaynor

2013-10-01

Imagery, as a cognitive strategy, can improve affective responses during moderate-intensity exercise. The effects of imagery at higher intensities of exercise have not been examined. Further, the effect of imagery use and activity in the frontal cortex during exercise is unknown. Using a crossover design (imagery and control), activity of the frontal cortex (reflected by changes in cerebral hemodynamics using near-infrared spectroscopy) and affective responses were measured during exercise at intensities 5% above the ventilatory threshold (VT) and the respiratory compensation point (RCP). Results indicated that imagery use influenced activity of the frontal cortex and was associated with a more positive affective response at intensities above VT, but not RCP to exhaustion (p < .05). These findings provide direct neurophysiological evidence of imagery use and activity in the frontal cortex during exercise at intensities above VT that positively impact affective responses.

Ultra-modified rapid sequence induction with transnasal humidified rapid insufflation ventilatory exchange: Challenging convention.

PubMed

Kulkarni, Ketan Sakharam; Dave, Nandini; Saran, Shriyam; Garasia, Madhu; Parelkar, Sandesh

2018-04-01

During positive pressure ventilation, gastric inflation and subsequent pulmonary aspiration can occur. Rapid sequence induction (RSI) technique is an age-old formula to prevent this. We adopted a novel approach of RSI for patients with high risk of aspiration and evaluated it further in patients undergoing laparoscopic surgeries. We believe that, in patients with risk of gastric insufflation and pulmonary aspiration, transnasal humidified rapid-insufflation ventilatory exchange can be useful in facilitating pre- and apnoeic oxygenation till tracheal isolation is achieved.

Exercise, Affect, and Adherence: An Integrated Model and a Case for Self-Paced Exercise

PubMed Central

Williams, David M.

2014-01-01

This paper reviews research relevant to a proposed conceptual model of exercise adherence that integrates the dual mode model and hedonic theory. Exercise intensity is posited to influence affective response to exercise via interoceptive (e.g., ventilatory drive) and cognitive (e.g., perceived autonomy) pathways; affective response to exercise is posited to influence exercise adherence via anticipated affective response to future exercise. The potential for self-paced exercise to enhance exercise adherence is examined in the context of the proposed model and suggestions are given for future research. Further evidence in support of self-paced exercise could have implications for exercise prescription, especially among overweight, sedentary adults, who are most in need of interventions that enhance adherence to exercise programs. PMID:18971508

Red Spinach Extract Increases Ventilatory Threshold during Graded Exercise Testing

PubMed Central

Kephart, Wesley C.; Holland, Angelia M.; Pascoe, David D.; Roberts, Michael D.

2017-01-01

Background: We examined the acute effect of a red spinach extract (RSE) (1000 mg dose; ~90 mg nitrate (NO3−)) on performance markers during graded exercise testing (GXT). Methods: For this randomized, double-blind, placebo (PBO)-controlled, crossover study, 15 recreationally-active participants (aged 23.1 ± 3.3 years; BMI: 27.2 ± 3.7 kg/m2) reported >2 h post-prandial and performed GXT 65–75 min post-RSE or PBO ingestion. Blood samples were collected at baseline (BL), pre-GXT (65–75 min post-ingestion; PRE), and immediately post-GXT (POST). GXT commenced with continuous analysis of expired gases. Results: Plasma concentrations of NO3− increased PRE (+447 ± 294%; p < 0.001) and POST (+378 ± 179%; p < 0.001) GXT with RSE, but not with PBO (+3 ± 26%, −8 ± 24%, respectively; p > 0.05). No effect on circulating nitrite (NO2−) was observed with RSE (+3.3 ± 7.5%, +7.7 ± 11.8% PRE and POST, respectively; p > 0.05) or PBO (−0.5 ± 7.9%, −0.2 ± 8.1% PRE and POST, respectively; p > 0.05). When compared to PBO, there was a moderate effect of RSE on plasma NO2− at PRE (g = 0.50 [−0.26, 1.24] and POST g = 0.71 [−0.05, 1.48]). During GXT, VO2 at the ventilatory threshold was significantly higher with RSE compared to PBO (+6.1 ± 7.3%; p < 0.05), though time-to-exhaustion (−4.0 ± 7.7%; p > 0.05) and maximal aerobic power (i.e., VO2 peak; −0.8 ± 5.6%; p > 0.05) were non-significantly lower with RSE. Conclusions: RSE as a nutritional supplement may elicit an ergogenic response by delaying the ventilatory threshold. PMID:29910440

The Prognostic Role of Ventilatory Inefficiency and Exercise Capacity in Idiopathic Pulmonary Fibrosis.

PubMed

Vainshelboim, Baruch; Oliveira, Jose; Fox, Benjamin Daniel; Kramer, Mordechai Reuven

2016-08-01

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease associated with poor prognosis and limited effective treatment options. Reliable predictors of outcome in daily clinical practice are needed to determine high-risk patients for urgent lung transplantation referral. This study aimed to identify practical prognostic predictors of mortality using cardiopulmonary exercise testing (CPET) in IPF subjects. Thirty-four subjects with IPF (22 men and 12 women), median age 68 (range 50-81) y were prospectively studied. At baseline, all subjects were assessed with CPET and were followed up for 40 months from baseline. Receiver operating characteristic curve analysis was conducted to determine cut-off points of CPET variables for mortality, Cox regression analysis for survival using a log-rank test, and hazard ratio for death using a Wald test. Peak work rate <62 watts (P = .005), peak V̇O2 ≤13.8 mL/kg/min (P = .031), tidal volume reserve ≤0.48 L/breath (P = .010), minute ventilation to carbon dioxide (V̇E)/V̇CO2 ) ratio at the anaerobic threshold >34 (P = .02), and V̇E)/V̇O2 nadir >34 (P = .002) were detected as cut-off points associated with mortality. Non-survivor subjects were characterized by higher dyspnea levels, the presence of pulmonary hypertension assessed by echocardiography, pronounced inefficient ventilatory pattern, lower exercise capacity, and more severe desaturation during physical exertion. By the end of the study, 11 subjects (7 women and 4 men) died. Overall mean survival was 60%, 33.7 months (95% CI 30.2-37.2). This study provides simple, practical, and novel cut-off points for CPET as predictors of prognosis to identify high-risk IPF subjects. Impairment in exercise capacity and abnormal ventilatory responses during CPET were associated with poorer survival in IPF subjects. The findings suggest considering the use of CPET for IPF risk stratification and prediction of prognosis. (ClinicalTrials.gov registration NCT01499745.). Copyright © 2016 by Daedalus Enterprises.

Hypercapnic acidosis modulates inflammation, lung mechanics, and edema in the isolated perfused lung.

PubMed

De Smet, Hilde R; Bersten, Andrew D; Barr, Heather A; Doyle, Ian R

2007-12-01

Low tidal volume (V(T)) ventilation strategies may be associated with permissive hypercapnia, which has been shown by ex vivo and in vivo studies to have protective effects. We hypothesized that hypercapnic acidosis may be synergistic with low V(T) ventilation; therefore, we studied the effects of hypercapnia and V(T) on unstimulated and lipopolysaccharide-stimulated isolated perfused lungs. Isolated perfused rat lungs were ventilated for 2 hours with low (7 mL/kg) or moderately high (20 mL/kg) V(T) and 5% or 20% CO(2), with lipopolysaccharide or saline added to the perfusate. Hypercapnia resulted in reduced pulmonary edema, lung stiffness, tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the lavage and perfusate. The moderately high V(T) did not cause lung injury but increased lavage IL-6 and perfusate IL-6 as well as TNF-alpha. Pulmonary edema and respiratory mechanics improved, possibly as a result of a stretch-induced increase in surfactant turnover. Lipopolysaccharide did not induce significant lung injury. We conclude that hypercapnia exerts a protective effect by modulating inflammation, lung mechanics, and edema. The moderately high V(T) used in this study stimulated inflammation but paradoxically improved edema and lung mechanics with an associated increase in surfactant release.

Utility of respiratory ward-based NIV in acidotic hypercapnic respiratory failure.

PubMed

Dave, Chirag; Turner, Alice; Thomas, Ajit; Beauchamp, Ben; Chakraborty, Biman; Ali, Asad; Mukherjee, Rahul; Banerjee, Dev

2014-11-01

We sought to elicit predictors of in-hospital mortality for first and subsequent admissions with acidotic hypercapnic respiratory failure (AHRF) in a cohort of chronic obstructive pulmonary disease patients who have undergone ward-based non-invasive ventilation (NIV), and identify features associated with long-term survival. Analysis of prospectively collected data at a single centre on patients undergoing NIV for AHRF between 2004 and 2009. Predictors of in-hospital mortality and intubation were sought by logistic regression and predictors of long-term survival by Cox regression. Initial pH exhibited a threshold effect for in-hospital mortality at pH 7.15. This relationship remained in patients undergoing their first episode of AHRF. In both first and subsequent admissions, a pH threshold of 7.25 at 4 h was associated with better prognosis (P = 0.02 and P = 0.04 respectively). In second or subsequent episodes of AHRF, mortality was lower and predicted only by age (P = 0.002) on multivariate analysis. NIV could be used on medical wards for patients with pH 7.16 or greater on their first admission, although more conservative values should continue to be used for those with a second or subsequent episodes of AHRF. © 2014 Asian Pacific Society of Respirology.

Soluble erythropoietin receptor is present in the mouse brain and is required for the ventilatory acclimatization to hypoxia

PubMed Central

Soliz, Jorge; Gassmann, Max; Joseph, Vincent

2007-01-01

While erythropoietin (Epo) and its receptor (EpoR) have been widely investigated in brain, the expression and function of the soluble Epo receptor (sEpoR) remain unknown. Here we demonstrate that sEpoR, a negative regulator of Epo's binding to the EpoR, is present in the mouse brain and is down-regulated by 62% after exposure to normobaric chronic hypoxia (10% O2 for 3 days). Furthermore, while normoxic minute ventilation increased by 58% in control mice following hypoxic acclimatization, sEpoR infusion in brain during the hypoxic challenge efficiently reduced brain Epo concentration and abolished the ventilatory acclimatization to hypoxia (VAH). These observations imply that hypoxic downregulation of sEpoR is required for adequate ventilatory acclimatization to hypoxia, thereby underlying the function of Epo as a key factor regulating oxygen delivery not only by its classical activity on red blood cell production, but also by regulating ventilation. PMID:17584830

Behavioural and Physiological Responses of Gammarus pulex Exposed to Cadmium and Arsenate at Three Temperatures: Individual and Combined Effects

PubMed Central

Vellinger, Céline; Felten, Vincent; Sornom, Pascal; Rousselle, Philippe; Beisel, Jean-Nicolas; Usseglio-Polatera, Philippe

2012-01-01

This study aimed at investigating both the individual and combined effects of cadmium (Cd) and arsenate (AsV) on the physiology and behaviour of the Crustacean Gammarus pulex at three temperatures (5, 10 and15°C). G. pulex was exposed during 96 h to (i) two [Cd] alone, (ii) two [AsV] alone, and (iii) four combinations of [Cd] and [AsV] to obtain a complete factorial plane. After exposure, survival, [AsV] or [Cd] in body tissues, behavioural (ventilatory and locomotor activities) and physiological responses (iono-regulation of [Na+] and [Cl−] in haemolymph) were examined. The interactive effects (antagonistic, additive or synergistic) of binary mixtures were evaluated for each tested temperature using a predictive model for the theoretically expected interactive effect of chemicals. In single metal exposure, both the internal metal concentration in body tissues and the mortality rate increased along metallic gradient concentration. Cd alone significantly impaired both [Na+] and [Cl−] while AsV alone had a weak impact only on [Cl−]. The behavioural responses of G. pulex declined with increasing metal concentration suggesting a reallocation of energy from behavioural responses to maintenance functions. The interaction between AsV and Cd was considered as ‘additive’ for all the tested binary mixtures and temperatures (except for the lowest combination at 10°C considered as “antagonistic”). In binary mixtures, the decrease in both ventilatory and locomotor activities and the decline in haemolymphatic [Cl−] were amplified when respectively compared to those observed with the same concentrations of AsV or Cd alone. However, the presence of AsV decreased the haemolymphatic [Na+] loss when G. pulex was exposed to the lowest Cd concentration. Finally, the observed physiological and behavioural effects (except ventilation) in G. pulex exposed to AsV and/or Cd were exacerbated under the highest temperature. The discussion encompasses both the toxicity mechanisms of these metals and their interaction with rising temperature. PMID:22761731

Ventilatory thresholds determined from HRV: comparison of 2 methods in obese adolescents.

PubMed

Quinart, S; Mourot, L; Nègre, V; Simon-Rigaud, M-L; Nicolet-Guénat, M; Bertrand, A-M; Meneveau, N; Mougin, F

2014-03-01

The development of personalised training programmes is crucial in the management of obesity. We evaluated the ability of 2 heart rate variability analyses to determine ventilatory thresholds (VT) in obese adolescents. 20 adolescents (mean age 14.3±1.6 years and body mass index z-score 4.2±0.1) performed an incremental test to exhaustion before and after a 9-month multidisciplinary management programme. The first (VT1) and second (VT2) ventilatory thresholds were identified by the reference method (gas exchanges). We recorded RR intervals to estimate VT1 and VT2 from heart rate variability using time-domain analysis and time-varying spectral-domain analysis. The coefficient correlations between thresholds were higher with spectral-domain analysis compared to time-domain analysis: Heart rate at VT1: r=0.91 vs. =0.66 and VT2: r=0.91 vs. =0.66; power at VT1: r=0.91 vs. =0.74 and VT2: r=0.93 vs. =0.78; spectral-domain vs. time-domain analysis respectively). No systematic bias in heart rate at VT1 and VT2 with standard deviations <6 bpm were found, confirming that spectral-domain analysis could replace the reference method for the detection of ventilatory thresholds. Furthermore, this technique is sensitive to rehabilitation and re-training, which underlines its utility in clinical practice. This inexpensive and non-invasive tool is promising for prescribing physical activity programs in obese adolescents. © Georg Thieme Verlag KG Stuttgart · New York.

RNASeq-derived transcriptome comparisons reveal neuromodulatory deficiency in the CO2 insensitive brown Norway rat

PubMed Central

Puissant, Madeleine M; Echert, Ashley E; Yang, Chun; Mouradian, Gary C; Novotny, Tyler; Liu, Pengyuan; Liang, Mingyu; Hodges, Matthew R

2015-01-01

Raphé-derived serotonin (5-HT) and thyrotropin-releasing hormone (TRH) play important roles in fundamental, homeostatic control systems such as breathing and specifically the ventilatory CO2 chemoreflex. Brown Norway (BN) rats exhibit an inherent and severe ventilatory insensitivity to hypercapnia but also exhibit relatively normal ventilation at rest and during other conditions, similar to multiple genetic models of 5-HT system dysfunction in mice. Herein, we tested the hypothesis that the ventilatory insensitivity to hypercapnia in BN rats is due to altered raphé gene expression and the consequent deficiencies in raphé-derived neuromodulators such as TRH. Medullary raphé transcriptome comparisons revealed lower expression of multiple 5-HT neuron-specific genes in BN compared to control Dahl salt-sensitive rats, predictive of reduced central nervous system monoamines by bioinformatics analyses and confirmed by high-performance liquid chromatography measurements. In particular, raphé Trh mRNA and peptide levels were significantly reduced in BN rats, and injections of the stable TRH analogue Taltirelin (TAL) stimulated breathing dose-dependently, with greater effects in BN versus control Sprague–Dawley rats. Importantly, TAL also effectively normalized the ventilatory CO2 chemoreflex in BN rats, but TAL did not affect CO2 sensitivity in control Sprague–Dawley rats. These data establish a molecular basis of the neuromodulatory deficiency in BN rats, and further suggest an important functional role for TRH signalling in the mammalian CO2 chemoreflex. PMID:25630262

Exertional dyspnea associated with chest wall strapping is reduced when external dead space substitutes for part of the exercise stimulus to ventilation.

PubMed

Garske, Luke A; Lal, Ravin; Stewart, Ian B; Morris, Norman R; Cross, Troy J; Adams, Lewis

2017-05-01

Chest wall strapping has been used to assess mechanisms of dyspnea with restrictive lung disease. This study examined the hypothesis that dyspnea with restriction depends principally on the degree of reflex ventilatory stimulation. We compared dyspnea at the same (iso)ventilation when added dead space provided a component of the ventilatory stimulus during exercise. Eleven healthy men undertook a randomized controlled crossover trial that compared four constant work exercise conditions: 1 ) control (CTRL): unrestricted breathing at 90% gas exchange threshold (GET); 2 ) CTRL+dead space (DS): unrestricted breathing with 0.6-l dead space, at isoventilation to CTRL due to reduced exercise intensity; 3 ) CWS: chest wall strapping at 90% GET; and 4 ) CWS+DS: chest strapping with 0.6-l dead space, at isoventilation to CWS with reduced exercise intensity. Chest strapping reduced forced vital capacity by 30.4 ± 2.2% (mean ± SE). Dyspnea at isoventilation was unchanged with CTRL+DS compared with CTRL (1.93 ± 0.49 and 2.17 ± 0.43, 0-10 numeric rating scale, respectively; P = 0.244). Dyspnea was lower with CWS+DS compared with CWS (3.40 ± 0.52 and 4.51 ± 0.53, respectively; P = 0.003). Perceived leg fatigue was reduced with CTRL+DS compared with CTRL (2.36 ± 0.48 and 2.86 ± 0.59, respectively; P = 0.049) and lower with CWS+DS compared with CWS (1.86 ± 0.30 and 4.00 ± 0.79, respectively; P = 0.006). With unrestricted breathing, dead space did not change dyspnea at isoventilation, suggesting that dyspnea does not depend on the mode of reflex ventilatory stimulation in healthy individuals. With chest strapping, dead space presented a less potent stimulus to dyspnea, raising the possibility that leg muscle work contributes to dyspnea perception independent of the ventilatory stimulus. NEW & NOTEWORTHY Chest wall strapping was applied to healthy humans to simulate restrictive lung disease. With chest wall strapping, dyspnea was reduced when dead space substituted for part of a constant exercise stimulus to ventilation. Dyspnea associated with chest wall strapping depended on the contribution of leg muscle work to ventilatory stimulation. Chest wall strapping might not be a clinically relevant model to determine whether an alternative reflex ventilatory stimulus mimics the intensity of exertional dyspnea. Copyright © 2017 the American Physiological Society.

Ventilatory Response to Hypercapnia Predicts Dementia with Lewy Bodies in Late-Onset Major Depressive Disorder.

PubMed

Takahashi, Sho; Mizukami, Katsuyoshi; Arai, Tetsuaki; Ogawa, Ryoko; Kikuchi, Norihiro; Hattori, Satoshi; Darby, David; Asada, Takashi

2016-01-01

Studies have shown that developing major depressive disorder (MDD) at 50 years of age or older can predict dementia. Depression is particularly common in dementia with Lewy bodies (DLB), and occasionally occurs before the onset of extrapyramidal symptoms. Moreover, systemic autonomic dysfunction, including an abnormal ventilatory response to hypercapnia (VRH), is common in patients with DLB. Here, we aimed to determine whether the VRH is useful for distinguishing depression that is predictive of DLB from other types of MDD. Participants were 35 consecutive patients with first onset MDD at 50 years or older with bradykinesia. After diagnosing the clinical subtype of MDD according to DSM-IV criteria, each subject underwent a battery of psychological tests, autonomic examinations including VRH, brain magnetic resonance imaging, and 123I-meta-iodobenzylguanidine scintigraphy. Longitudinal follow-up showed that all 18 patients with abnormal VRH results developed DLB, whereas none of the 17 patients with normal VRH results converted to DLB within the study period (sensitivity: 100% , specificity: 100%). Additionally, over half of the DLB converters showed abnormalities on other autonomic examinations. For converters, the most common MDD subtype had psychotic and melancholic features simultaneously. The frequency of hypersensitivity to psychotropics was higher in converters than it was in non-converters. In the present study, patients with abnormal VRH results were very likely to develop DLB. Thus, for patients with late-onset MDD accompanied by bradykinesia, the VRH in combination with the clinical subtype of MDD or hypersensitivity to psychotropics may be useful for diagnosing prodromal DLB.

Sleep disorders associated with primary mitochondrial diseases.

PubMed

Ramezani, Ryan J; Stacpoole, Peter W

2014-11-15

Primary mitochondrial diseases are caused by heritable or spontaneous mutations in nuclear DNA or mitochondrial DNA. Such pathological mutations are relatively common in humans and may lead to neurological and neuromuscular complication that could compromise normal sleep behavior. To gain insight into the potential impact of primary mitochondrial disease and sleep pathology, we reviewed the relevant English language literature in which abnormal sleep was reported in association with a mitochondrial disease. We examined publication reported in Web of Science and PubMed from February 1976 through January 2014, and identified 54 patients with a proven or suspected primary mitochondrial disorder who were evaluated for sleep disturbances. Both nuclear DNA and mitochondrial DNA mutations were associated with abnormal sleep patterns. Most subjects who underwent polysomnography had central sleep apnea, and only 5 patients had obstructive sleep apnea. Twenty-four patients showed decreased ventilatory drive in response to hypoxia and/ or hyperapnea that was not considered due to weakness of the intrinsic muscles of respiration. Sleep pathology may be an underreported complication of primary mitochondrial diseases. The probable underlying mechanism is cellular energy failure causing both central neurological and peripheral neuromuscular degenerative changes that commonly present as central sleep apnea and poor ventilatory response to hyperapnea. Increased recognition of the genetics and clinical manifestations of mitochondrial diseases by sleep researchers and clinicians is important in the evaluation and treatment of all patients with sleep disturbances. Prospective population-based studies are required to determine the true prevalence of mitochondrial energy failure in subjects with sleep disorders, and conversely, of individuals with primary mitochondrial diseases and sleep pathology. © 2014 American Academy of Sleep Medicine.

Intracarotid substance P infusion inhibits ventilation in the goat.

PubMed

Pizarro, J; Ryan, M L; Hedrick, M S; Xue, D H; Keith, I M; Bisgard, G E

1995-07-01

Substance P (SP) has been proposed as an excitatory neuromodulator of the carotid body (CB) response to hypoxia based on data from the cat and rat. The role of SP as a CB neuromodulator in the goat is unknown. Awake (n = 14) and chloralose anesthetized goats (n = 6) were used to investigate the effects of intracarotid (IC) SP infusions (1-6 micrograms.kg-1.min-1) and bolus injections (6 micrograms kg-1) to the CB intact and denervated (CBX) sides (control) on mean ventilation (VE) and mean blood pressure (MBP). In awake goats VE was decreased by infusion or bolus SP injection at a dose of 6 micrograms.kg-1 (P < 0.05) and occurred with infusions to the intact or CBX sides. MBP was elevated with SP infusion to either the CB intact or CBX sides at all SP doses. The SP antagonist CP-96,345 (0.1 mg.kg-1, IV) blocked the decrease in VE induced by SP in normoxia and significantly increased the hypoxic ventilatory response (PaO2 = 40 torr). In anesthetized goats, IC injections of SP (1 to 6 micrograms.kg-1) reduced phrenic activity and MBP before and after CBX. In only one of five goats airway pressure was increased suggesting that bronchoconstriction was not a cause for the reduced ventilatory and phrenic activity induced by SP. Immunohistochemistry provided evidence of SP in CB nerve fibers and terminals, carotid sinus nerve axons and petrosal ganglion cells, but not in type I glomus cells. Our results do not support the view that SP is an excitatory neuromodulator of CB chemotransduction in the goat.

Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI)

NASA Technical Reports Server (NTRS)

Gelfand, R.; Lambertsen, C. J.; Clark, J. M.; Hopkin, E.

1998-01-01

Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2 therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

Contribution of peripheral and central chemoreceptors to sympatho‐excitation in heart failure

PubMed Central

Toledo, Camilo; Andrade, David C.; Lucero, Claudia; Schultz, Harold D.; Marcus, Noah; Retamal, Mauricio; Madrid, Carlos

2016-01-01

Abstract Chronic heart failure (CHF) is a major public health problem. Tonic hyper‐activation of sympathetic neural outflow is commonly observed in patients with CHF. Importantly, sympatho‐excitation in CHF exacerbates its progression and is strongly related to poor prognosis and high mortality risk. Increases in both peripheral and central chemoreflex drive are considered markers of the severity of CHF. The principal peripheral chemoreceptors are the carotid bodies (CBs) and alteration in their function has been described in CHF. Mainly, during CHF the CB chemosensitivity is enhanced leading to increases in ventilation and sympathetic outflow. In addition to peripheral control of breathing, central chemoreceptors (CCs) are considered a dominant mechanism in ventilatory regulation. Potentiation of the ventilatory and sympathetic drive in response to CC activation has been shown in patients with CHF as well as in animal models. Therefore, improving understanding of the contribution of the peripheral and central chemoreflexes to augmented sympathetic discharge in CHF could help in developing new therapeutic approaches intended to attenuate the progression of CHF. Accordingly, the main focus of this review is to discuss recent evidence that peripheral and central chemoreflex function are altered in CHF and that they contribute to autonomic imbalance and progression of CHF. PMID:27218485

Activation of microglia and astrocytes in the nucleus tractus solitarius during ventilatory acclimatization to 10% hypoxia in unanesthetized mice.

PubMed

Tadmouri, A; Champagnat, J; Morin-Surun, M P

2014-05-01

Nucleus tractus solitarius (NTS) is the integrative sensory relay of autonomic functions in the brainstem. To explore the nonneuronal cellular basis of central chemosensitivity during the first 24 hr of ventilatory acclimatization to hypoxia (VHA), we have investigated glial activation markers in the NTS. Conscious mice (C57/BL6) were placed in a hermetic hypoxia chamber containing a plethysmograph to record ventilation. After 4 days of habituation to the normoxic environment, mice were subjected to physiological hypoxia (10% O2 ) for 1, 6, or 24 hr. To dissociate interactions between microglia and astrocytes, another group received daily minocycline, a microglia activation blocker. By immunochemical localization of astrocytes (GFAP), activated microglia (Cd11b), and total microglia (Iba-1), we identified an oxygen-sensing glial layer in the NTS, in which astrocytes are first activated after 1-6 hr of hypoxia, followed by microglia after 6-24 hr of hypoxia. Minocycline administration suppressed microglial activation and decreased astrocyte activation at 6 hr and VHA at 24 hr of hypoxia. These results suggest that astrocytes contribute to the neuronal response during the first hour of hypoxia, whereas microglial cells, via cross-talk with astrocytes, are involved in the VHA during the first 24 hr of acclimatization. Copyright © 2014 Wiley Periodicals, Inc.

Historical perspectives of cellular oxygen sensing and responses to hypoxia.

PubMed

Lahiri, S

2000-04-01

The responses to acute and chronic hypoxia begin with oxygen sensing, and this historical perspective is written in line with this concept. The earliest pertinent work started with studies on fermentation in yeast in the 17th century, before the discovery of oxygen. It required 200 yr to localize the oxygen sensing within the cells and another 100 yr to discover the cellular oxidation reactions. Today, the consensus is that the mitochondrial respiratory chain is in part the site of oxygen sensing. In addition, membrane-bound NAD(P)H oxidase possibly takes part in oxygen sensing. Oxygen-sensing mechanisms occur in a tissue-specific fashion. For example, the carotid body responds to hypoxia promptly by eliciting a ventilatory response, whereas erythropoietin production in response to hypoxia requires more time, involving new expression of genes. The mechanism has therefore moved from the cells to genes.

Affect, exercise, and physical activity among healthy adolescents.

PubMed

Schneider, Margaret; Dunn, Andrea; Cooper, Daniel

2009-12-01

Many adolescents do not meet public health recommendations for moderate-to-vigorous physical activity (MVPA). In studies of variables influencing adolescent MVPA, one that has been understudied is the affective response to exercise. We hypothesized that adolescents with a more positive affective response to acute exercise would be more active. Adolescents (N = 124; 46% male) completed two 30-min exercise tasks (above and below the ventilatory threshold [VT]), and wore ActiGraph accelerometers for 6.5 +/- 0.7 days. Affective valence was assessed before, during, and after each task. A more positive affective response during exercise below the VT was associated with greater participation in MVPA (p < .05). The results are consistent with the hypothesis that individuals who have a more positive affective response to exercise will engage in more MVPA. To promote greater participation in MVPA among adolescents, programs should be designed to facilitate a positive affective experience during exercise.

Intra-oral ignition of monopolar diathermy during transnasal humidified rapid-insufflation ventilatory exchange (THRIVE).

PubMed

Onwochei, D; El-Boghdadly, K; Oakley, R; Ahmad, I

2017-06-01

We present the case of unanticipated airway ignition during hard palate biopsy. Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) and monopolar diathermy were utilised for the procedure, during which an arc arose from the diathermy tip to a titanium implant, causing a brief ignition on the monopolar diathermy grip. This case highlights the need for maintained awareness of fire risk when using diathermy in the presence of THRIVE during airway surgery. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

Ventilatory Cycle Measurements and Loop Gain in Central Apnea in Mining Drivers Exposed to Intermittent Altitude.

PubMed

Rey de Castro, Jorge; Liendo, Alicia; Ortiz, Oswaldo; Rosales-Mayor, Edmundo; Liendo, César

2017-01-15

By measuring the apnea length, ventilatory phase, respiratory cycle length, and loop gain, we can further characterize the central apneas of high altitude (CAHA). Sixty-three drivers of all-terrain vehicles, working in a Peruvian mine located at 2,020 meters above sea level (MASL), were evaluated. A respiratory polygraph was performed in the first night they slept at high altitude. None of the subjects were exposed to oxygen during the test or acetazolamide in the preceding days of the test. Sixty-three respiratory polygraphs were performed, and 59 were considered for analysis. Forty-six (78%) were normal, 6 (10%) had OSA, and 7 (12%) had CAHA. Key data from subjects include: residing altitude: 341 ± 828 MASL, Lake Louise scoring: 0.4 ± 0.8, Epworth score: 3.4 ± 2.7, apneahypopnea index: 35.7 ± 19.3, CA index: 13.4 ± 14.2, CA length: 14.4 ± 3.6 sec, ventilatory length: 13.5 ± 2.9 sec, cycle length: 26.5 ± 4.0 sec, ventilatory length/CA length ratio 0.9 ± 0.3 and circulatory delay 13.3 ± 2.9 sec. Duty ratio media [ventilatory duration/cycle duration] was 0.522 ± 0 0.128 [0.308-0.700] and loop gain was calculated from the duty ratio utilizing this formula: LG = 2π / [(2πDR-sin(2πDR)]. All subjects have a high loop gain media 2.415 ± 1.761 [1.175-6.260]. Multiple correlations were established with loop gain values, but the only significant correlation detected was between central apnea index and loop gain. Twelve percent of the studied population had CAHA. Measurements of respiratory cycle in workers with CAHA are more similar to idiopathic central apneas rather than Hunter-Cheyne-Stokes respiration. Also, there was a high degree of correlation between severity of central apnea and the degree of loop gain. The abnormal breathing patterns in those subjects could affect the sleep quality and potentially increase the risk for work accidents. © 2017 American Academy of Sleep Medicine

Sonotubometry, a useful tool for the evaluation of the Eustachian tube ventilatory function

PubMed Central

Borangiu, A; Popescu, CR; Purcarea, VL

2014-01-01

From the three Eustachian tube (ET) functions: middle ear protection, secretion clearance and middle ear ventilation, the ventilatory function is unanimously considered the most important one, because proper hearing is established only when tympanic membrane compliance is normal. This requires equilibrium between the middle ear and ambient gas pressure, which makes the normal functioning of active ET opening of critical importance. There are several methods and tests that can assess such a complex and variable mechanism. Sonotubometry is one such method; despite the fact that it has been continuously improved in the last 20 years, it is not yet systematically used to evaluate the ET ventilatory function, because its measurement pattern, context mapping (patient, clinic data, medication, treatment), validation, reproducibility and value for clinic practice, have not yet been fully consolidated and integrated in a knowledge-based, service-oriented system, that can provide decision support or even diagnostic. The paper reviews the role of tubal sonometry as a non-invasive, physiologic and easy to use method in assessing the ventilatory function and investigates the validity and reproducibility of a measuring pattern and test in a group of children. The paper describes the test pattern used, and the computer-based platform based on: (1) Digital Signal Processing (DSP) for sound acquisition and low-level processing; (2) Artificial Intelligence techniques to extract significant sound features from sonotubograms and learn a manifold context database. Results are reported from test series carried out in healthy children; a similar study between tests is included in the final Discussions section. PMID:25713631

Pulmonary outcome of esophageal atresia patients and its potential causes in early childhood.

PubMed

Dittrich, René; Stock, Philippe; Rothe, Karin; Degenhardt, Petra

2017-08-01

The aim of this study was to illustrate the pulmonary long term outcome of patients with repaired esophageal atresia and to further examine causes and correlations that might have led to this outcome. Twenty-seven of 62 possible patients (43%) aged 5-20years, with repaired esophageal atresia were recruited. Body plethysmography and spirometry were performed to evaluate lung function, and the Bruce protocol treadmill exercise test to assess physical fitness. Results were correlated to conditions such as interpouch distance, gastroesophageal reflux or duration of post-operative mechanical ventilation. Seventeen participants (63%) showed abnormal lung function at rest or after exercise. Restrictive ventilatory defects (solely restrictive or combined) were found in 11 participants (41%), and obstructive ventilatory defects (solely obstructive or combined) in 13 subjects (48%). Twenty-two participants (81%) performed the Bruce protocol treadmill exercise test to standard. The treadmill exercise results were expressed in z-score and revealed to be significantly below the standard population mean (z-score=-1.40). Moreover, significant correlations between restrictive ventilatory defects and the interpouch distance; duration of post-operative ventilation; gastroesophageal reflux disease; plus recurrent aspiration pneumonia during infancy; were described. It was shown that esophageal atresia and associated early complications have significant impact on pulmonary long term outcomes such as abnormal lung function and, in particular restrictive ventilatory defects. Long-running and regular follow-ups of patients with congenital esophageal atresia are necessary in order to detect and react to the development and progression of associated complications such as ventilation disorders or gastroesophageal reflux disease. Prognosis study, Level II. Copyright © 2016 Elsevier Inc. All rights reserved.

Prolonged exposure to elevated CO(2) promotes growth of the algal symbiont Symbiodinium muscatinei in the intertidal sea anemone Anthopleura elegantissima.

PubMed

Towanda, Trisha; Thuesen, Erik V

2012-07-15

Some photosynthetic organisms benefit from elevated levels of carbon dioxide, but studies on the effects of elevated PCO(2) on the algal symbionts of animals are very few. This study investigated the impact of hypercapnia on a photosynthetic symbiosis between the anemone Anthopleura elegantissima and its zooxanthella Symbiodinium muscatinei. Anemones were maintained in the laboratory for 1 week at 37 Pa PCO(2) and pH 8.1. Clonal pairs were then divided into two groups and maintained for 6 weeks under conditions naturally experienced in their intertidal environment, 45 Pa PCO(2), pH 8.1 and 231 Pa PCO(2), pH 7.3. Respiration and photosynthesis were measured after the 1-week acclimation period and after 6 weeks in experimental conditions. Density of zooxanthellal cells, zooxanthellal cell size, mitotic index and chlorophyll content were compared between non-clonemate anemones after the 1-week acclimation period and clonal anemones at the end of the experiment. Anemones thrived in hypercapnia. After 6 weeks, A. elegantissima exhibited higher rates of photosynthesis at 45 Pa (4.2 µmol O(2) g(-1) h(-1)) and 231 Pa (3.30 µmol O(2) g(-1) h(-1)) than at the initial 37 Pa (1.53 µmol O(2) g(-1) h(-1)). Likewise, anemones at 231 Pa received more of their respiratory carbon from zooxanthellae (CZAR  = 78.2%) than those at 37 Pa (CZAR  = 66.6%) but less than anemones at 45 Pa (CZAR  = 137.3%). The mitotic index of zooxanthellae was significantly greater in the hypercapnic anemones than in anemones at lower PCO(2). Excess zooxanthellae were expelled by their hosts, and cell densities, cell diameters and chlorophyll contents were not significantly different between the groups. The response of A. elegantissima to hypercapnic acidification reveals the potential adaptation of an intertidal, photosynthetic symbiosis for high PCO(2).

Prolonged exposure to elevated CO2 promotes growth of the algal symbiont Symbiodinium muscatinei in the intertidal sea anemone Anthopleura elegantissima

PubMed Central

Towanda, Trisha; Thuesen, Erik V.

2012-01-01

Summary Some photosynthetic organisms benefit from elevated levels of carbon dioxide, but studies on the effects of elevated PCO2 on the algal symbionts of animals are very few. This study investigated the impact of hypercapnia on a photosynthetic symbiosis between the anemone Anthopleura elegantissima and its zooxanthella Symbiodinium muscatinei. Anemones were maintained in the laboratory for 1 week at 37 Pa PCO2 and pH 8.1. Clonal pairs were then divided into two groups and maintained for 6 weeks under conditions naturally experienced in their intertidal environment, 45 Pa PCO2, pH 8.1 and 231 Pa PCO2, pH 7.3. Respiration and photosynthesis were measured after the 1-week acclimation period and after 6 weeks in experimental conditions. Density of zooxanthellal cells, zooxanthellal cell size, mitotic index and chlorophyll content were compared between non-clonemate anemones after the 1-week acclimation period and clonal anemones at the end of the experiment. Anemones thrived in hypercapnia. After 6 weeks, A. elegantissima exhibited higher rates of photosynthesis at 45 Pa (4.2 µmol O2 g−1 h−1) and 231 Pa (3.30 µmol O2 g−1 h−1) than at the initial 37 Pa (1.53 µmol O2 g−1 h−1). Likewise, anemones at 231 Pa received more of their respiratory carbon from zooxanthellae (CZAR  = 78.2%) than those at 37 Pa (CZAR  = 66.6%) but less than anemones at 45 Pa (CZAR  = 137.3%). The mitotic index of zooxanthellae was significantly greater in the hypercapnic anemones than in anemones at lower PCO2. Excess zooxanthellae were expelled by their hosts, and cell densities, cell diameters and chlorophyll contents were not significantly different between the groups. The response of A. elegantissima to hypercapnic acidification reveals the potential adaptation of an intertidal, photosynthetic symbiosis for high PCO2. PMID:23213455

[Cheyne-Stokes respiration and cardiovascular risk].

PubMed

Duchna, H-W; Schultze-Werninghaus, G

2009-07-01

Due to its high prevalence in patients with heart failure and its negative predictive value concerning morbidity and mortality, Cheyne-Stokes respiration (CSR) is a sleep disorders of major interest. CSR correlates with the degree of heart failure and is characterised by a typical crescendo/decrescendo breathing pattern combined with phases of central sleep apnoea, caused by pulmonary oedema and oscillation of ventilatory control. Thus, CSR is a marker of the severity of heart failure. Treatment of CSR first involves optimisation of heart failure therapy by cardiologists and then application of non-invasive means of ventilatory support. Treatment of patients with severe heart failure with non-invasive positive pressure ventilatory support leads to a significant reduction of CSR, sympathetic activity, and daytime sleepiness and improves cardiac output and 6-minute walking distance. At present, a prospective randomised, controlled intervention-study (Serve-HF study) is being conducted in order to show if therapy of CSR can improve patient survival. This review describes the pathophysiology, epidemiology, and therapeutic options of CSR with a special focus on the elevated cardiovascular risk of patients with CSR.

Comparative study of lung functions in women working in different fibre industries.

PubMed

Khanam, F; Islam, N; Hai, M A

2008-07-01

A cross sectional work has been done on Bangladeshi females, working in different fibre industries, to study the effect of exposure to fibre dust on pulmonary functions. The ventilatory capacities were measured by VMI ventilometer in 653 apparently healthy women (160, 162 and 167 were jute, textile and garment industry workers, respectively). For the controls 164 females were recruited who never worked in any fibre industry. The observed FVC, FEV1 and PEFR were lower in all groups of fibre industry workers than those of the control. Among the industry workers, the jute mill workers had the lowest ventilatory capacities and garment industry workers had the highest values. The jute and textile mill workers had also significantly lower FEV1 and PEFR than those of garment industry workers. The FEV1 and PEFR were significantly lower in jute mill workers than those of textile ill workers. The low ventilatory capacities were almost proportionate with the length of service of the workers. Thus, the present study indicates that the fibre dust, on regular exposure for longer duration, may limit the lung functions.

HIF-1 and ventilatory acclimatization to chronic hypoxia

PubMed Central

Powell, Frank L.; Fu, Zhenxing

2008-01-01

Ventilatory acclimatization to hypoxia (VAH) is a time-dependent increase in ventilation and ventilatory O2-sensitivity that involves plasticity in carotid body chemoreceptors and CNS respiratory centers. Hypoxia inducible factor-1α (HIF-1α) controls the expression of several genes that increase physiological O2 supply. Studies using transgenic mice show HIF-1α expression in the carotid bodies and CNS with chronic sustained and intermittent hypoxia is important for VAH. Other O2-sensitive transcription factors such as HIF-2α may be important for VAH by reducing metabolic O2 demands also. Specific gene targets of HIF-1α shown to be involved in VAH include erythropoietin, endothelin-1, neuronal nitric oxide synthase and tyrosine hydroxylase. Other HIF-1α targets that may be involved in VAH include vascular endothelial growth factor, heme oxygenase 1 and cytoglobin. Interactions between these multiple pathways and feedback control of HIF-1α expression from some of the targets support a complex and powerful role for HIF-1α in neural plasticity of physiological control circuits with chronic hypoxia. PMID:18708172

Two-year home-based nocturnal noninvasive ventilation added to rehabilitation in chronic obstructive pulmonary disease patients: A randomized controlled trial

PubMed Central

2011-01-01

Background The use of noninvasive intermittent positive pressure ventilation (NIPPV) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure remains controversial as long-term data are almost lacking. The aim was to compare the outcome of 2-year home-based nocturnal NIPPV in addition to rehabilitation (NIPPV + PR) with rehabilitation alone (PR) in COPD patients with chronic hypercapnic respiratory failure. Methods Sixty-six patients could be analyzed for the two-year home-based follow-up period. Differences in change between the NIPPV + PR and PR group were assessed by a linear mixed effects model with a random effect on the intercept, and adjustment for baseline values. The primary outcome was health-related quality of life (HRQoL); secondary outcomes were mood state, dyspnea, gas exchange, functional status, pulmonary function, and exacerbation frequency. Results Although the addition of NIPPV did not significantly improve the Chronic Respiratory Questionnaire compared to rehabilitation alone (mean difference in change between groups -1.3 points (95% CI: -9.7 to 7.4)), the addition of NIPPV did improve HRQoL assessed with the Maugeri Respiratory Failure questionnaire (-13.4% (-22.7 to -4.2; p = 0.005)), mood state (Hospital Anxiety and Depression scale -4.0 points (-7.8 to 0.0; p = 0.05)), dyspnea (Medical Research Council -0.4 points (-0.8 to -0.0; p = 0.05)), daytime arterial blood gases (PaCO2 -0.4 kPa (-0.8 to -0.2; p = 0.01); PaO2 0.8 kPa (0.0 to 1.5; p = 0.03)), 6-minute walking distance (77.3 m (46.4 to 108.0; p < 0.001)), Groningen Activity and Restriction scale (-3.8 points (-7.4 to -0.4; p = 0.03)), and forced expiratory volume in 1 second (115 ml (19 to 211; p = 0.019)). Exacerbation frequency was not changed. Conclusions The addition of NIPPV to pulmonary rehabilitation for 2 years in severe COPD patients with chronic hypercapnic respiratory failure improves HRQoL, mood, dyspnea, gas exchange, exercise tolerance and lung function decline. The benefits increase further with time. Trial registration ClinicalTrials.Gov (ID NCT00135538). PMID:21861914

Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.

PubMed

Gordon, J B; Rehorst-Paea, L A; Hoffman, G M; Nelin, L D

1999-12-01

Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis.

Post-hypercapnic alkalosis is associated with ventilator dependence and increased ICU stay.

PubMed

Banga, Amit; Khilnani, G C

2009-12-01

Posthypercapnic alkalosis (PHA) is frequently overlooked as a complication of mechanical ventilation in patients with exacerbation of chronic obstructive pulmonary disease (COPD). The current study was conducted to determine the incidence, risk factors for development and effect on outcome of PHA. Eighty-four patients (62 +/- 11 years, range 42-78 years, M:F 58: 26) with exacerbation of COPD with underlying chronic hypercapnic respiratory failure requiring mechanical ventilation were included in a retrospective fashion. PHA was defined as static or rising serum bicarbonate levels, 72 hours or more after return of PaCO2 to baseline, with concurrent pH > 7.44. Development of PHA was noted in 17 patients (20.2%). Corticosteroid use >or=10 days during the hospital stay was an independent risk factor for development of PHA (Adjusted OR, 95% CI: 9.4, 1.6-55.3; P = 0.013). Development of PHA was associated with an increased incidence of ventilator dependence (64.7% vs. 37.3%, OR, 95% CI: 3.1, 1.1-9.4, P = 0.04) and duration of ICU stay (14.7 +/- 6.7 vs. 9.5 +/- 5.9, P = 0.01) but no increase in hospital mortality (43.3% vs. 41.2%, P = NS). It is concluded that PHA is a common complication in patients with exacerbation of COPD requiring mechanical ventilation and is associated with increased incidence of ventilator dependence and ICU stay.

Clinical outcomes of patients requiring ventilatory support in Brazilian intensive care units: a multicenter, prospective, cohort study

PubMed Central

2013-01-01

Introduction Contemporary information on mechanical ventilation (MV) use in emerging countries is limited. Moreover, most epidemiological studies on ventilatory support were carried out before significant developments, such as lung protective ventilation or broader application of non-invasive ventilation (NIV). We aimed to evaluate the clinical characteristics, outcomes and risk factors for hospital mortality and failure of NIV in patients requiring ventilatory support in Brazilian intensive care units (ICU). Methods In a multicenter, prospective, cohort study, a total of 773 adult patients admitted to 45 ICUs over a two-month period requiring invasive ventilation or NIV for more than 24 hours were evaluated. Causes of ventilatory support, prior chronic health status and physiological data were assessed. Multivariate analysis was used to identifiy variables associated with hospital mortality and NIV failure. Results Invasive MV and NIV were used as initial ventilatory support in 622 (80%) and 151 (20%) patients. Failure with subsequent intubation occurred in 54% of NIV patients. The main reasons for ventilatory support were pneumonia (27%), neurologic disorders (19%) and non-pulmonary sepsis (12%). ICU and hospital mortality rates were 34% and 42%. Using the Berlin definition, acute respiratory distress syndrome (ARDS) was diagnosed in 31% of the patients with a hospital mortality of 52%. In the multivariate analysis, age (odds ratio (OR), 1.03; 95% confidence interval (CI), 1.01 to 1.03), comorbidities (OR, 2.30; 95% CI, 1.28 to 3.17), associated organ failures (OR, 1.12; 95% CI, 1.05 to 1.20), moderate (OR, 1.92; 95% CI, 1.10 to 3.35) to severe ARDS (OR, 2.12; 95% CI, 1.01 to 4.41), cumulative fluid balance over the first 72 h of ICU (OR, 2.44; 95% CI, 1.39 to 4.28), higher lactate (OR, 1.78; 95% CI, 1.27 to 2.50), invasive MV (OR, 2.67; 95% CI, 1.32 to 5.39) and NIV failure (OR, 3.95; 95% CI, 1.74 to 8.99) were independently associated with hospital mortality. The predictors of NIV failure were the severity of associated organ dysfunctions (OR, 1.20; 95% CI, 1.05 to 1.34), ARDS (OR, 2.31; 95% CI, 1.10 to 4.82) and positive fluid balance (OR, 2.09; 95% CI, 1.02 to 4.30). Conclusions Current mortality of ventilated patients in Brazil is elevated. Implementation of judicious fluid therapy and a watchful use and monitoring of NIV patients are potential targets to improve outcomes in this setting. Trial registration ClinicalTrials.gov NCT01268410. PMID:23557378

Clinical Usefulness of Response Profiles to Rapidly Incremental Cardiopulmonary Exercise Testing

PubMed Central

Ramos, Roberta P.; Alencar, Maria Clara N.; Treptow, Erika; Arbex, Flávio; Ferreira, Eloara M. V.; Neder, J. Alberto

2013-01-01

The advent of microprocessed “metabolic carts” and rapidly incremental protocols greatly expanded the clinical applications of cardiopulmonary exercise testing (CPET). The response normalcy to CPET is more commonly appreciated at discrete time points, for example, at the estimated lactate threshold and at peak exercise. Analysis of the response profiles of cardiopulmonary responses at submaximal exercise and recovery, however, might show abnormal physiologic functioning which would not be otherwise unraveled. Although this approach has long been advocated as a key element of the investigational strategy, it remains largely neglected in practice. The purpose of this paper, therefore, is to highlight the usefulness of selected submaximal metabolic, ventilatory, and cardiovascular variables in different clinical scenarios and patient populations. Special care is taken to physiologically justify their use to answer pertinent clinical questions and to the technical aspects that should be observed to improve responses' reproducibility and reliability. The most recent evidence in favor of (and against) these variables for diagnosis, impairment evaluation, and prognosis in systemic diseases is also critically discussed. PMID:23766901

Arousal Intensity is a Distinct Pathophysiological Trait in Obstructive Sleep Apnea

PubMed Central

Amatoury, Jason; Azarbarzin, Ali; Younes, Magdy; Jordan, Amy S.; Wellman, Andrew; Eckert, Danny J.

2016-01-01

Study Objectives: Arousals from sleep vary in duration and intensity. Accordingly, the physiological consequences of different types of arousals may also vary. Factors that influence arousal intensity are only partly understood. This study aimed to determine if arousal intensity is mediated by the strength of the preceding respiratory stimulus, and investigate other factors mediating arousal intensity and its role on post-arousal ventilatory and pharyngeal muscle responses. Methods: Data were acquired in 71 adults (17 controls, 54 obstructive sleep apnea patients) instrumented with polysomnography equipment plus genioglossus and tensor palatini electromyography (EMG), a nasal mask and pneumotachograph, and an epiglottic pressure sensor. Transient reductions in CPAP were delivered during sleep to induce respiratory-related arousals. Arousal intensity was measured using a validated 10-point scale. Results: Average arousal intensity was not related to the magnitude of the preceding respiratory stimuli but was positively associated with arousal duration, time to arousal, rate of change in epiglottic pressure and negatively with BMI (R2 > 0.10, P ≤ 0.006). High (> 5) intensity arousals caused greater ventilatory responses than low (≤ 5) intensity arousals (10.9 [6.8–14.5] vs. 7.8 [4.7–12.9] L/min; P = 0.036) and greater increases in tensor palatini EMG (10 [3–17] vs. 6 [2–11]%max; P = 0.031), with less pronounced increases in genioglossus EMG. Conclusions: Average arousal intensity is independent of the preceding respiratory stimulus. This is consistent with arousal intensity being a distinct trait. Respiratory and pharyngeal muscle responses increase with arousal intensity. Thus, patients with higher arousal intensities may be more prone to respiratory control instability. These findings are important for sleep apnea pathogenesis. Citation: Amatoury J, Azarbarzin A, Younes M, Jordan AS, Wellman A, Eckert DJ. Arousal intensity is a distinct pathophysiological trait in obstructive sleep apnea. SLEEP 2016;39(12):2091–2100. PMID:27784404

Specificity Elicits Higher Maximal and Submaximal Cardiorespiratory Responses During a New Taekwondo Aerobic Test.

PubMed

Hausen, Matheus; Soares, Pedro Paulo; Araujo, Marcus Paulo; Esteves, Débora; Julio, Hilbert; Tauil, Roberto; Junca, Marcus; Porto, Flávia; Franchini, Emerson; Bridge, Craig Alan; Gurgel, Jonas

2018-05-10

The purpose of the present study was to propose and validate new taekwondo-specific cardiopulmonary exercise tests. Twelve male national-level taekwondo athletes (age 20 ± 2 yrs; body mass 67.5 ± 5.7 kg; height 175 ± 8 cm; training experience 7 ± 3 yrs) performed three separate exercise tests in a randomized counterbalanced order: 1) a Treadmill Running Cardiopulmonary Exercise Test (CPET); 2) Continuous and 3) Interval Taekwondo Cardiopulmonary Exercise Tests (cTKDet and iTKDet, respectively). The CPET was administered using an individualized ramp protocol. Taekwondo tests comprised sequences of turning kicks performed upon a stationary target. The impacts were recorded via an electronic scoring sensor used in official competition. Stages on the cTKDet and iTKDet lasted 1-min and progressively reduced the kick interval duration. These were guided by a sound signal, starting with 4.6s between kicks and reducing by 0.4s every minute until the test ended. Oxygen uptake (V̇O 2 ), heart rate (HR), capillary blood lactate and ratings of perceived exertion were measured. Modest differences were identified in V̇O 2MAX between the tests (F 2,22 =3.54; p=0.046; ES=0.16). HR MAX was higher during both taekwondo tests (F 2,22 =14.3; p=0.001; ES=1.14) compared with CPET. Specific tests also yielded higher responses in the 1 st ventilatory threshold V̇O 2 (F 2,22 =6.5; p=0.04; ES=0.27) and HR (F 2,22 =12.3; p<0.001; ES=1.06), and HR at the 2 nd ventilatory threshold (F 2,22 =5.7; p=0.02; ES=0.72). Taekwondo-specific cardiopulmonary tests enhance the validity of some cardiopulmonary responses, and might therefore be considered to optimise routine diagnostic testing and training prescription for this athletic group.

Cardiorespiratory responses of a dance session designed for older women: A cross sectional study.

PubMed

Rodrigues-Krause, Josianne; Farinha, Juliano Boufleur; Ramis, Thiago Rozales; Boeno, Francesco Pinto; Dos Santos, Gabriela Cristina; Krause, Mauricio; Reischak-Oliveira, Alvaro

2018-06-04

Dancing has been increasingly used as a type of exercise intervention to improve cardiovascular fitness of older people. However, it is unclear which may be the exercise intensity of the dance sessions. To describe cardiorespiratory responses of a dance session for older women, and to identify intensity zones in relation to peak oxygen consumption (VO 2 peak), first and second ventilatory thresholds (VT1 and VT2). Ten women (66 ± 5 yrs., BMI 27 ± 4) were examined on three occasions: Familiarization, maximum effort and dance sessions. Incremental treadmill test: 5 km/h, 2% slope each min, until maximum effort. Dance class (60 min): warm-up (20 min), across-the-floor (10 min), choreography (15 min), show (10 min) and cool-down (5 min). Ventilatory parameters were measured continuously (breath-by-breath). VO 2 (mL·kg -1 ·min -1 ): Maximum effort: VO 2 peak (23.3 ± 4.3), VT1 (17.2 ± 3.5) and VT2 (20.9 ± 3.4). Dancing: warm-up (12.8 ± 2.4, ~55%VO 2 peak), across-the-floor (14.2 ± 2.4 ~62%VO 2 peak), choreography (14.6 ± 3.2 ~63%VO 2 peak) and show (16.1 ± 3.3, ~69% VO 2 peak). Show was similar to VT1. Cardiorespiratory demands of a dance class for older women are at low aerobic intensity. Show was similar to VT1, indicating that a dance class may be modulated to improve aerobic fitness, at least at initial stages of training. Copyright © 2018 Elsevier Inc. All rights reserved.

Physiologic response to varying levels of pressure support and neurally adjusted ventilatory assist in patients with acute respiratory failure.

PubMed

Colombo, Davide; Cammarota, Gianmaria; Bergamaschi, Valentina; De Lucia, Marta; Corte, Francesco Della; Navalesi, Paolo

2008-11-01

Neurally adjusted ventilatory assist (NAVA) is a new mode wherein the assistance is provided in proportion to diaphragm electrical activity (EAdi). We assessed the physiologic response to varying levels of NAVA and pressure support ventilation (PSV). ICU of a University Hospital. Fourteen intubated and mechanically ventilated patients. DESIGN AND PROTOCOL: Cross-over, prospective, randomized controlled trial. PSV was set to obtain a VT/kg of 6-8 ml/kg with an active inspiration. NAVA was matched with a dedicated software. The assistance was decreased and increased by 50% with both modes. The six assist levels were randomly applied. Arterial blood gases (ABGs), tidal volume (VT/kg), peak EAdi, airway pressure (Paw), neural and flow-based timing. Asynchrony was calculated using the asynchrony index (AI). There was no difference in ABGs regardless of mode and assist level. The differences in breathing pattern, ventilator assistance, and respiratory drive and timing between PSV and NAVA were overall small at the two lower assist levels. At the highest assist level, however, we found greater VT/kg (9.1 +/- 2.2 vs. 7.1 +/- 2 ml/kg, P < 0.001), and lower breathing frequency (12 +/- 6 vs. 18 +/- 8.2, P < 0.001) and peak EAdi (8.6 +/- 10.5 vs. 12.3 +/- 9.0, P < 0.002) in PSV than in NAVA; we found mismatch between neural and flow-based timing in PSV, but not in NAVA. AI exceeded 10% in five (36%) and no (0%) patients with PSV and NAVA, respectively (P < 0.05). Compared to PSV, NAVA averted the risk of over-assistance, avoided patient-ventilator asynchrony, and improved patient-ventilator interaction.

Ventilatory gas exchange and early response to cardiac resynchronization therapy.

PubMed

Kim, Chul-Ho; Olson, Lyle J; Shen, Win K; Cha, Yong-Mei; Johnson, Bruce D

2015-11-01

Cardiac resynchronization therapy (CRT) is an accepted intervention for chronic heart failure (HF), although approximately 30% of patients are non-responders. The purpose of this study was to determine whether exercise respiratory gas exchange obtained before CRT implantation predicts early response to CRT. Before CRT implantation, patients were assigned to either a mild-moderate group (Mod G, n = 33, age 67 ± 10 years) or a moderate-severe group (Sev G, n = 31, age 67 ± 10 years), based on abnormalities in exercise gas exchange. Severity of impaired gas exchange was based on a score from the measures of VE/VCO(2) slope, resting PETCO(2) and change of PETCO(2) from resting to peak. All measurements were performed before and 3 to 4 months after CRT implantation. Although Mod G did not have improved gas exchange (p > 0.05), Sev G improved significantly (p < 0.05) post-CRT. In addition, Mod G did not show improved right ventricular systolic pressure (RSVP; pre vs post: 37 ± 14 vs 36 ± 11 mm Hg, p > 0.05), yet Sev G showed significantly improved RVSP, by 23% (50 ± 14 vs 42 ± 12 mm Hg, p < 0.05). Both groups had improved left ventricular ejection fraction (p < 0.05), New York Heart Association class (p < 0.05) and quality of life (p < 0.05), but no significant differences were observed between groups (p > 0.05). No significant changes were observed in brain natriuretic peptide in either group post-CRT. Based on pre-CRT implantation ventilatory gas exchange, subjects with the most impaired values appeared to have more improvement post-CRT, possibly associated with a decrease in RVSP. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Impaired central respiratory chemoreflex in an experimental genetic model of epilepsy

PubMed Central

Totola, Leonardo T.; Takakura, Ana C.; Oliveira, José Antonio C.

2016-01-01

Key points It is recognized that seizures commonly cause apnoea and oxygen desaturation, but there is still a lack in the literature about the respiratory impairments observed ictally and in the post‐ictal period.Respiratory disorders may involve changes in serotonergic transmission at the level of the retrotrapezoid nucleus (RTN).In this study, we evaluated breathing activity and the role of serotonergic transmission in the RTN with a rat model of tonic–clonic seizures, the Wistar audiogenic rat (WAR).We conclude that the respiratory impairment in the WAR could be correlated to an overall decrease in the number of neurons located in the respiratory column. Abstract Respiratory disorders may involve changes in serotonergic neurotransmission at the level of the chemosensitive neurons located in the retrotrapezoid nucleus (RTN). Here, we investigated the central respiratory chemoreflex and the role of serotonergic neurotransmission in the RTN with a rat model of tonic–clonic seizures, the Wistar audiogenic rat (WAR). We found that naive or kindled WARs have reduced resting ventilation and ventilatory response to hypercapnia (7% CO2). The number of chemically coded (Phox2b+/TH−) RTN neurons, as well as the serotonergic innervation to the RTN, was reduced in WARs. We detected that the ventilatory response to serotonin (1 mm, 50 nl) within the RTN region was significantly reduced in WARs. Our results uniquely demonstrated a respiratory impairment in a genetic model of tonic–clonic seizures, the WAR strain. More importantly, we demonstrated an overall decrease in the number of neurons located in the ventral respiratory column (VRC), as well as a reduction in serotonergic neurons in the midline medulla. This is an important step forward to demonstrate marked changes in neuronal activity and breathing impairment in the WAR strain, a genetic model of epilepsy. PMID:27633663

Effect of different ventilatory strategies on local and systemic cytokine production in intact swine lungs in vivo.

PubMed

Myrianthefs, P; Boutzouka, E; Venetsanou, K; Papalois, A; Kouloukousa, M; Kittas, C; Baltopoulos, G

2006-05-01

The purpose of the study was to investigate the effect of different ventilatory strategies on local and systemic cytokine production in swine with intact lungs in vivo after 4 h of mechanical ventilation. Twenty-five swine were anesthetized and then randomized into five groups (n = 5): (1) low tidal volume zero PEEP (LVZP); (2) medium tidal volume zero PEEP (MVZP); (3) high tidal volume zero PEEP (HVZP); (4) low tidal volume PEEP (LVP); (4) high tidal volume PEEP (HVP). Respiratory rate was adjusted to maintain normocapnia and fraction of inspired oxygen (FiO2) was 1.0. TNF-alpha and IL-10 were measured in BALF and serum at baseline, 2 h, and 4 h of MV. One animal in LVZP (2 h) and two in HVP (3 h) group died before the end of the experiment. TNF-alpha level in BALF was significantly higher in LVZP and LVP at 4 h compared to baseline and the other groups. IL-10 level in BALF was significantly higher in LVP at 4h compared to baseline and the other groups. There was a statistically significant increase in serum TNF-alpha levels at 4 h in LVP group compared to baseline and the other groups at 4 h. There was statistically significant increase in serum IL-10 levels in HVZP and LVP groups at 2 and 4 h which was significantly higher compared to the other groups at 4 h. Our results show that a) low volume MV may induce local and systemic pro- and anti-inflammatory cytokine increase b) in the presence of pro-inflammatory cytokine response there is also an anti-inflammatory response in the same compartment (lungs, circulation). c) There maybe loss of alveolar-to-systemic cytokine compartmentalization.

Glutamate receptors in the nucleus tractus solitarius contribute to ventilatory acclimatization to hypoxia in rat

PubMed Central

Pamenter, Matthew E; Carr, J Austin; Go, Ariel; Fu, Zhenxing; Reid, Stephen G; Powell, Frank L

2014-01-01

When exposed to a hypoxic environment the body's first response is a reflex increase in ventilation, termed the hypoxic ventilatory response (HVR). With chronic sustained hypoxia (CSH), such as during acclimatization to high altitude, an additional time-dependent increase in ventilation occurs, which increases the HVR. This secondary increase persists after exposure to CSH and involves plasticity within the circuits in the central nervous system that control breathing. Currently these mechanisms of HVR plasticity are unknown and we hypothesized that they involve glutamatergic synapses in the nucleus tractus solitarius (NTS), where afferent endings from arterial chemoreceptors terminate. To test this, we treated rats held in normoxia (CON) or 10% O2 (CSH) for 7 days and measured ventilation in conscious, unrestrained animals before and after microinjecting glutamate receptor agonists and antagonists into the NTS. In normoxia, AMPA increased ventilation 25% and 50% in CON and CSH, respectively, while NMDA doubled ventilation in both groups (P < 0.05). Specific AMPA and NMDA receptor antagonists (NBQX and MK801, respectively) abolished these effects. MK801 significantly decreased the HVR in CON rats, and completely blocked the acute HVR in CSH rats but had no effect on ventilation in normoxia. NBQX decreased ventilation whenever it was increased relative to normoxic controls; i.e. acute hypoxia in CON and CSH, and normoxia in CSH. These results support our hypothesis that glutamate receptors in the NTS contribute to plasticity in the HVR with CSH. The mechanism underlying this synaptic plasticity is probably glutamate receptor modification, as in CSH rats the expression of phosphorylated NR1 and GluR1 proteins in the NTS increased 35% and 70%, respectively, relative to that in CON rats. PMID:24492841

Glutamate receptors in the nucleus tractus solitarius contribute to ventilatory acclimatization to hypoxia in rat.

PubMed

Pamenter, Matthew E; Carr, J Austin; Go, Ariel; Fu, Zhenxing; Reid, Stephen G; Powell, Frank L

2014-04-15

When exposed to a hypoxic environment the body's first response is a reflex increase in ventilation, termed the hypoxic ventilatory response (HVR). With chronic sustained hypoxia (CSH), such as during acclimatization to high altitude, an additional time-dependent increase in ventilation occurs, which increases the HVR. This secondary increase persists after exposure to CSH and involves plasticity within the circuits in the central nervous system that control breathing. Currently these mechanisms of HVR plasticity are unknown and we hypothesized that they involve glutamatergic synapses in the nucleus tractus solitarius (NTS), where afferent endings from arterial chemoreceptors terminate. To test this, we treated rats held in normoxia (CON) or 10% O2 (CSH) for 7 days and measured ventilation in conscious, unrestrained animals before and after microinjecting glutamate receptor agonists and antagonists into the NTS. In normoxia, AMPA increased ventilation 25% and 50% in CON and CSH, respectively, while NMDA doubled ventilation in both groups (P < 0.05). Specific AMPA and NMDA receptor antagonists (NBQX and MK801, respectively) abolished these effects. MK801 significantly decreased the HVR in CON rats, and completely blocked the acute HVR in CSH rats but had no effect on ventilation in normoxia. NBQX decreased ventilation whenever it was increased relative to normoxic controls; i.e. acute hypoxia in CON and CSH, and normoxia in CSH. These results support our hypothesis that glutamate receptors in the NTS contribute to plasticity in the HVR with CSH. The mechanism underlying this synaptic plasticity is probably glutamate receptor modification, as in CSH rats the expression of phosphorylated NR1 and GluR1 proteins in the NTS increased 35% and 70%, respectively, relative to that in CON rats.

Effects of septum and pericardium on heart-lung interactions in a cardiopulmonary simulation model.

PubMed

Karamolegkos, Nikolaos; Albanese, Antonio; Chbat, Nicolas W

2017-07-01

Mechanical heart-lung interactions are often overlooked in clinical settings. However, their impact on cardiac function can be quite significant. Mechanistic physiology-based models can provide invaluable insights into such cardiorespiratory interactions, which occur not only under external mechanical ventilatory support but in normal physiology as well. In this work, we focus on the cardiac component of a previously developed mathematical model of the human cardiopulmonary system, aiming to improve the model's response to the intrathoracic pressure variations that are associated with the respiratory cycle. Interventricular septum and pericardial membrane are integrated into the existing model. Their effect on the overall cardiac response is explained by means of comparison against simulation results from the original model as well as experimental data from literature.

Controversies in the physiological basis of the 'anaerobic threshold' and their implications for clinical cardiopulmonary exercise testing.

PubMed

Hopker, J G; Jobson, S A; Pandit, J J

2011-02-01

This article reviews the notion of the 'anaerobic threshold' in the context of cardiopulmonary exercise testing. Primarily, this is a review of the proposed mechanisms underlying the ventilatory and lactate response to incremental exercise, which is important to the clinical interpretation of an exercise test. Since such tests are often conducted for risk stratification before major surgery, a failure to locate or justify the existence of an anaerobic threshold will have some implications for clinical practice. We also consider alternative endpoints within the exercise response that might be better used to indicate a patient's capacity to cope with the metabolic demands encountered both during and following major surgery. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

Use of 'ideal' alveolar air equations and corrected end-tidal PCO2 to estimate arterial PCO2 and physiological dead space during exercise in patients with heart failure.

PubMed

Van Iterson, Erik H; Olson, Thomas P

2018-01-01

Arterial CO 2 tension (PaCO 2 ) and physiological dead space (V D ) are not routinely measured during clinical cardiopulmonary exercise testing (CPET). Abnormal changes in PaCO 2 accompanied by increased V D directly contribute to impaired exercise ventilatory function in heart failure (HF). Because arterial catheterization is not standard practice during CPET, this study tested the construct validity of PaCO 2 and V D prediction models using 'ideal' alveolar air equations and basic ventilation and gas-exchangegas exchange measurements during CPET in HF. Forty-seven NYHA class II/III HF (LVEF=21±7%; age=55±9years; male=89%; BMI=28±5kg/m 2 ) performed step-wise cycle ergometry CPET to volitional fatigue. Breath-by-breath ventilation and gas exchange were measured continuously. Steady-state PaCO 2 was measured at rest and peak exercise via radial arterial catheterization. Criterion V D was calculated via 'ideal' alveolar equations, whereas PaCO 2 or V D models were based on end-tidal CO 2 tension (P ET CO 2 ), tidal volume (V T ), and/or weight. Criterion measurements of PaCO 2 (38±5 vs. 33±5mmHg, P<0.01) and V D (0.26±0.07 vs. 0.41±0.15L, P<0.01) differed at rest vs. peak exercise, respectively. The equation, 5.5+0.90×P ET CO 2 -0.0021×V T , was the strongest predictor of PaCO 2 at rest and peak exercise (bias±95%LOA=-3.24±6.63 and -0.98±5.76mmHg; R 2 =0.57 and 0.75, P<0.001, respectively). This equation closely predicted V D at rest and peak exercise (bias±95%LOA=-0.03±0.06 and -0.02±0.13L; R 2 =0.86 and 0.83, P<0.001, respectively). These data suggest predicted PaCO 2 and V D based on breath-by-breath gas exchange and ventilatory responses demonstrate acceptable agreement with criterion measurements at peak exercise in HF patients. Routine assessment of PaCO 2 and V D can be used to improve interpretability of exercise ventilatory responses in HF. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Use of cardiopulmonary exercise testing to assess early ventilatory changes related to occupational particulate matter

PubMed Central

Chao, T.P.; Sperandio, E.F.; Ostolin, T.L.V.P.; Almeida, V.R.; Romiti, M.; Gagliardi, A.R.T.; Arantes, R.L.; Dourado, V.Z.

2018-01-01

Spirometry has been used as the main strategy for assessing ventilatory changes related to occupational exposure to particulate matter (OEPM). However, in some cases, as one of its limitations, it may not be sensitive enough to show abnormalities before extensive damage, as seen in restrictive lung diseases. Therefore, we hypothesized that cardiopulmonary exercise testing (CPET) may be better than spirometry to detect early ventilatory impairment caused by OEPM. We selected 135 male workers with at least one year of exposure. After collection of self-reported socioeconomic status, educational level, and cardiovascular risk data, participants underwent spirometry, CPET, body composition assessment (bioelectrical impedance), and triaxial accelerometry (for level of physical activity in daily life). CPET was performed using a ramp protocol on a treadmill. Metabolic, cardiovascular, ventilatory, and submaximal relationships were measured. We compared 52 exposed to 83 non-exposed workers. Multiple linear regressions were developed using spirometry and CPET variables as outcomes and OEPM as the main predictor, and adjusted by the main covariates. Our results showed that OEPM was associated with significant reductions in peak minute ventilation, peak tidal volume, and breathing reserve index. Exposed participants presented shallower slope of ΔVT/ΔlnV̇E (breathing pattern), i.e., increased tachypneic breathing pattern. The OEPM explained 7.4% of the ΔVT/ΔlnV̇E variability. We found no significant influence of spirometric indices after multiple linear regressions. We conclude that CPET might be a more sensitive feature of assessing early pulmonary impairment related to OEPM. Our cross-sectional results suggested that CPET is a promising tool for the screening of asymptomatic male workers. PMID:29590255

Anaerobic threshold assessment through the ventilatory method during roller-ski skating testing: right or wrong?

PubMed

Fabre, Nicolas; Bortolan, Lorenzo; Pellegrini, Barbara; Zerbini, Livio; Mourot, Laurent; Schena, Federico

2012-02-01

This study aimed at questioning the validity of the ventilatory method to determine the anaerobic threshold (respiratory compensation point [RCP]) during an incremental roller-ski skating test to exhaustion. Nine elite crosscountry skiers were evaluated. The skiers carried out an incremental roller-ski test on a treadmill with the V2 skating technique. Ventilatory parameters were continuously collected breath by breath, thanks to a portable gas exchange measurement system. Poling signal was obtained using instrumented ski poles. For each stage, ventilatory and poling signals were synchronized and averaged. The poor coefficient of interobserver reliability for the time at RCP confirmed the great difficulty felt by the 3 blinded reviewers for the RCP determination. Moreover, the reviewer agreed with the impossibility of determining RCP in 4 of the 9 skiers. There was no significant difference between breathing frequency (Bf) and poling frequency (Pf) during the last 8 stages. However, it seems that the differences observed during the first stages arose from the use of either a strictly 1:1 or a 1:2 Bf to Pf ratio when the exercise intensity was still moderate. So, even if there were significant differences between the frequencies, the Bf was strictly subordinate to the Pf during the entire test. In the same way, the normalized tidal volume and peak poling forces curves were superposable. These findings showed that when the upper body is mainly involved in the propulsion, the determinants of the ventilation are strictly dependent on the poling pattern during an incremental test to exhaustion. Thus, during roller-ski skating, the determination of RCP must be used cautiously because too much depending on mechanical factors.

Respiratory constraints during activities in daily life and the impact on health status in patients with early-stage COPD: a cross-sectional study.

PubMed

van Helvoort, Hanneke Ac; Willems, Laura M; Dekhuijzen, Pn Richard; van Hees, Hieronymus Wh; Heijdra, Yvonne F

2016-10-13

In patients with chronic obstructive pulmonary disease (COPD), exercise capacity is reduced, resulting over time in physical inactivity and worsened health status. It is unknown whether ventilatory constraints occur during activities of daily life (ADL) in early stages of COPD. The aim of this study was to assess respiratory mechanics during ADL and to study its consequences on dyspnoea, physical activity and health status in early-stage COPD compared with healthy controls. In this cross-sectional study, 39 early-stage COPD patients (mean FEV 1 88±s.d. 12% predicted) and 20 controls performed 3 ADL: climbing stairs, vacuum cleaning and displacing groceries in a cupboard. Respiratory mechanics were measured during ADL. Physical activity was measured with accelerometry. Health status was assessed by the Nijmegen Clinical Screening Instrument. Compared with controls, COPD patients had greater ventilatory inefficiency and higher ventilatory requirements during ADL (P<0.05). Dyspnoea scores were increased in COPD compared with controls (P<0.001). During ADL, >50% of the patients developed dynamic hyperinflation in contrast to 10-35% of the controls. Higher dyspnoea was scored by patients with dynamic hyperinflation. Physical activity was low but comparable between both groups. From the patients, 55-84% experienced mild-to-severe problems in health status compared with 5-25% of the controls. Significant ventilatory constraints already occur in early-stage COPD patients during common ADL and result in increased dyspnoea. Physical activity level is not yet reduced, but many patients already experience limitations in health status. These findings reinforce the importance of early diagnosis of COPD and assessment of more than just spirometry.

Ventilatory mechanics and the effects of water depth on breathing pattern in the aquatic caecilian Typhlonectes natans.

PubMed

Prabha, K C; Bernard, D G; Gardner, M; Smatresk, N J

2000-01-01

The breathing pattern in the aquatic caecilian Typhlonectes natans was investigated by recording airflow via a pneumotachograph under unrestrained normal physiological conditions. Ventilatory mechanics were assessed using airflow and pressure measurements from the buccal cavity and trachea. The breathing pattern consisted of an expiratory phase followed by a series of 10-15 small buccal pumps to inflate the lung, succeeded by a long non-ventilatory period. T. natans separate the expiratory and inspiratory gases in the buccal cavity and take several inspiratory pumps, distinguishing their breathing pattern from that of sarcopterygians. Hydrostatic pressure assisted exhalation. The tracheal pressure was greater than the water pressure at that depth, suggesting that pleuroperitoneal pressure as well as axial or pulmonary smooth muscles may have contributed to the process of exhalation. The frequency of lung ventilation was 6.33+/-0.84 breaths h(-)(1), and ventilation occurred via the nares. Compared with other amphibians, this low ventilatory frequency suggests that T. natans may have acquired very efficient pulmonary respiration as an adaptation for survival in their seasonally fluctuating natural habitat. Their respiratory pathway is quite unique, with the trachea separated into anterior, central and posterior regions. The anterior region serves as an air channel, the central region is attached to the tracheal lung, and the posterior region consists of a bifurcated air channel leading to the left and right posterior lungs. The lungs are narrow, elongated, profusely vascularized and compartmentalized. The posterior lungs extend to approximately two-thirds of the body length. On the basis of their breathing pattern, it appears that caecilians are phylogenetically derived from two-stroke breathers.

Neurally adjusted ventilatory assist in patients with acute respiratory failure: study protocol for a randomized controlled trial.

PubMed

Villar, Jesús; Belda, Javier; Blanco, Jesús; Suarez-Sipmann, Fernando; Añón, José Manuel; Pérez-Méndez, Lina; Ferrando, Carlos; Parrilla, Dácil; Montiel, Raquel; Corpas, Ruth; González-Higueras, Elena; Pestaña, David; Martínez, Domingo; Fernández, Lorena; Soro, Marina; García-Bello, Miguel Angel; Fernández, Rosa Lidia; Kacmarek, Robert M

2016-10-13

Patient-ventilator asynchrony is a common problem in mechanically ventilated patients with acute respiratory failure. It is assumed that asynchronies worsen lung function and prolong the duration of mechanical ventilation (MV). Neurally Adjusted Ventilatory Assist (NAVA) is a novel approach to MV based on neural respiratory center output that is able to trigger, cycle, and regulate the ventilatory cycle. We hypothesized that the use of NAVA compared to conventional lung-protective MV will result in a reduction of the duration of MV. It is further hypothesized that NAVA compared to conventional lung-protective MV will result in a decrease in the length of ICU and hospital stay, and mortality. This is a prospective, multicenter, randomized controlled trial in 306 mechanically ventilated patients with acute respiratory failure from several etiologies. Only patients ventilated for less than 5 days, and who are expected to require prolonged MV for an additional 72 h or more and are able to breathe spontaneously, will be considered for enrollment. Eligible patients will be randomly allocated to two ventilatory arms: (1) conventional lung-protective MV (n = 153) and conventional lung-protective MV with NAVA (n = 153). Primary outcome is the number of ventilator-free days, defined as days alive and free from MV at day 28 after endotracheal intubation. Secondary outcomes are total length of MV, and ICU and hospital mortality. This is the first randomized clinical trial examining, on a multicenter scale, the beneficial effects of NAVA in reducing the dependency on MV of patients with acute respiratory failure. ClinicalTrials.gov website ( NCT01730794 ). Registered on 15 November 2012.

The nucleus reticularis gigantocellularis modulates the cardiopulmonary responses to central and peripheral drives related to exercise.

PubMed

Richard, C A; Waldrop, T G; Bauer, R M; Mitchell, J H; Stremel, R W

1989-03-13

It is known that muscle afferents and the hypothalamic locomotor region (HLR) both project to the nucleus reticularis gigantocellularis (NGC) and that the NGC is capable of influencing cardiovascular and respiratory variables. Therefore, the role of NGC in the cardiovascular and respiratory response to exercise-related signals was investigated in anesthetized cats. These signals were generated by stimulation of: (1) spinal ventral roots to induce hindlimb muscle contraction (MC) and (2) the HLR. Bilateral electrolytic lesion of the NGC at the pontomedullary border caused tidal volume, respiratory frequency and heart rate responses to HLR stimulation to be greater than the responses recorded prior to lesioning. Lesioning had no effect on the ventilatory or cardiovascular responses to MC but did decrease phrenic responsiveness; lesion had no effect on any resting values. In this preparation, the pontomedullary NGC acts as an inhibitory influence on tidal volume, breathing frequency and heart rate responses to the central command for exercise. In addition, NGC modulation of ventilation would appear to be selective for certain respiratory muscle groups.

Robot-Assisted End-Effector-Based Stair Climbing for Cardiopulmonary Exercise Testing: Feasibility, Reliability, and Repeatability.

PubMed

Stoller, Oliver; Schindelholz, Matthias; Hunt, Kenneth J

2016-01-01

Neurological impairments can limit the implementation of conventional cardiopulmonary exercise testing (CPET) and cardiovascular training strategies. A promising approach to provoke cardiovascular stress while facilitating task-specific exercise in people with disabilities is feedback-controlled robot-assisted end-effector-based stair climbing (RASC). The aim of this study was to evaluate the feasibility, reliability, and repeatability of augmented RASC-based CPET in able-bodied subjects, with a view towards future research and applications in neurologically impaired populations. Twenty able-bodied subjects performed a familiarisation session and 2 consecutive incremental CPETs using augmented RASC. Outcome measures focussed on standard cardiopulmonary performance parameters and on accuracy of work rate tracking (RMSEP-root mean square error). Criteria for feasibility were cardiopulmonary responsiveness and technical implementation. Relative and absolute test-retest reliability were assessed by intraclass correlation coefficients (ICC), standard error of the measurement (SEM), and minimal detectable change (MDC). Mean differences, limits of agreement, and coefficients of variation (CoV) were estimated to assess repeatability. All criteria for feasibility were achieved. Mean V'O2peak was 106±9% of predicted V'O2max and mean HRpeak was 99±3% of predicted HRmax. 95% of the subjects achieved at least 1 criterion for V'O2max, and the detection of the sub-maximal ventilatory thresholds was successful (ventilatory anaerobic threshold 100%, respiratory compensation point 90% of the subjects). Excellent reliability was found for peak cardiopulmonary outcome measures (ICC ≥ 0.890, SEM ≤ 0.60%, MDC ≤ 1.67%). Repeatability for the primary outcomes was good (CoV ≤ 0.12). RASC-based CPET with feedback-guided exercise intensity demonstrated comparable or higher peak cardiopulmonary performance variables relative to predicted values, achieved the criteria for V'O2max, and allowed determination of sub-maximal ventilatory thresholds. The reliability and repeatability were found to be high. There is potential for augmented RASC to be used for exercise testing and prescription in populations with neurological impairments who would benefit from repetitive task-specific training.

Robot-Assisted End-Effector-Based Stair Climbing for Cardiopulmonary Exercise Testing: Feasibility, Reliability, and Repeatability

PubMed Central

Stoller, Oliver; Schindelholz, Matthias; Hunt, Kenneth J.

2016-01-01

Background Neurological impairments can limit the implementation of conventional cardiopulmonary exercise testing (CPET) and cardiovascular training strategies. A promising approach to provoke cardiovascular stress while facilitating task-specific exercise in people with disabilities is feedback-controlled robot-assisted end-effector-based stair climbing (RASC). The aim of this study was to evaluate the feasibility, reliability, and repeatability of augmented RASC-based CPET in able-bodied subjects, with a view towards future research and applications in neurologically impaired populations. Methods Twenty able-bodied subjects performed a familiarisation session and 2 consecutive incremental CPETs using augmented RASC. Outcome measures focussed on standard cardiopulmonary performance parameters and on accuracy of work rate tracking (RMSEP−root mean square error). Criteria for feasibility were cardiopulmonary responsiveness and technical implementation. Relative and absolute test-retest reliability were assessed by intraclass correlation coefficients (ICC), standard error of the measurement (SEM), and minimal detectable change (MDC). Mean differences, limits of agreement, and coefficients of variation (CoV) were estimated to assess repeatability. Results All criteria for feasibility were achieved. Mean V′O2peak was 106±9% of predicted V′O2max and mean HRpeak was 99±3% of predicted HRmax. 95% of the subjects achieved at least 1 criterion for V′O2max, and the detection of the sub-maximal ventilatory thresholds was successful (ventilatory anaerobic threshold 100%, respiratory compensation point 90% of the subjects). Excellent reliability was found for peak cardiopulmonary outcome measures (ICC ≥ 0.890, SEM ≤ 0.60%, MDC ≤ 1.67%). Repeatability for the primary outcomes was good (CoV ≤ 0.12). Conclusions RASC-based CPET with feedback-guided exercise intensity demonstrated comparable or higher peak cardiopulmonary performance variables relative to predicted values, achieved the criteria for V′O2max, and allowed determination of sub-maximal ventilatory thresholds. The reliability and repeatability were found to be high. There is potential for augmented RASC to be used for exercise testing and prescription in populations with neurological impairments who would benefit from repetitive task-specific training. PMID:26849137

Mechanical ventilatory constraints during incremental cycle exercise in human pregnancy: implications for respiratory sensation

PubMed Central

Jensen, Dennis; Webb, Katherine A; Davies, Gregory A L; O'Donnell, Denis E

2008-01-01

The aim of this study was to identify the physiological mechanisms of exertional respiratory discomfort (breathlessness) in pregnancy by comparing ventilatory (breathing pattern, airway function, operating lung volumes, oesophageal pressure (Poes)-derived indices of respiratory mechanics) and perceptual (breathlessness intensity) responses to incremental cycle exercise in 15 young, healthy women in the third trimester (TM3; between 34 and 38 weeks gestation) and again 4–5 months postpartum (PP). During pregnancy, resting inspiratory capacity (IC) increased (P < 0.01) and end-expiratory lung volume decreased (P < 0.001), with no associated change in total lung capacity (TLC) or static respiratory muscle strength. This permitted greater tidal volume (VT) expansion throughout exercise in TM3, while preserving the relationship between contractile respiratory muscle effort (tidal Poes swing expressed as a percentage of maximum inspiratory pressure (PImax)) and thoracic volume displacement (VT expressed as a percentage of vital capacity) and between breathlessness and ventilation (V̇E). At the highest equivalent work rate (HEWR = 128 ± 5 W) in TM3 compared with PP: V̇E, tidal Poes/PImax and breathlessness intensity ratings increased by 10.2 l min−1 (P < 0.001), 8.8%PImax (P < 0.05) and 0.9 Borg units (P < 0.05), respectively. Pulmonary resistance was not increased at rest or during exercise at the HEWR in TM3, despite marked increases in mean tidal inspiratory and expiratory flow rates, suggesting increased bronchodilatation. Dynamic mechanical constraints on VT expansion (P < 0.05) with associated increased breathlessness intensity ratings (P < 0.05) were observed near peak exercise in TM3 compared with PP. In conclusion: (1) pregnancy-induced increases in exertional breathlessness reflected the normal awareness of increased V̇E and contractile respiratory muscle effort; (2) mechanical adaptations of the respiratory system, including recruitment of resting IC and increased bronchodilatation, accommodated the increased VT while preserving effort–displacement and breathlessness–V̇E relationships; and (3) dynamic mechanical ventilatory constraints contributed to respiratory discomfort near the limits of tolerance in late gestation. PMID:18687714

The impact of arousal state, sex, and sleep apnea on the magnitude of progressive augmentation and ventilatory long-term facilitation.

PubMed

Syed, Ziauddin; Lin, Ho-Sheng; Mateika, Jason H

2013-01-01

We examined the impact of arousal state, sex, and obstructive sleep apnea (OSA) on the magnitude of progressive augmentation of the hypoxic ventilatory response and ventilatory long-term facilitation (vLTF). We also examined whether exposure to intermittent hypoxia during sleep has an impact on the apnea-hypopnea index (AHI) in individuals with OSA. Ten men and seven women with OSA, along with ten healthy men and ten healthy women, were exposed to twelve 2-min episodes of hypoxia (end-tidal PO(2): 50 Torr) in the presence of sustained hypercapnia (end-tidal PCO(2): 3 Torr above baseline), followed by a 30-min recovery period during wakefulness and sleep. The OSA participants completed an additional sham study during sleep. The AHI during the first hour of sleep following the intermittent hypoxia and sham protocols were compared. Progressive augmentation was only evident during wakefulness and was enhanced in the OSA participants. vLTF was evident during wakefulness and sleep. When standardized to baseline, vLTF was greater during wakefulness and was enhanced in the OSA group (men: wakefulness 1.39 ± 0.08 vs. sleep 1.14 ± 0.03; women: wakefulness 1.35 ± 0.03 vs. sleep 1.16 ± 0.05 fraction of baseline; P ≤ 0.001) compared with control (men: wakefulness 1.19 ± 0.03 vs. sleep 1.09 ± 0.03; women: wakefulness 1.26 ± 0.05 vs. sleep 1.08 ± 0.04 fraction of baseline; P ≤ 0.001). The AHI following exposure to intermittent hypoxia was increased (intermittent hypoxia 72.8 ± 7.3 vs. sham 56.5 ± 7.0 events/h; P ≤ 0.01). Sex-related differences were not observed for the primary measures. We conclude that progressive augmentation is not evident, and the magnitude of vLTF is diminished during sleep compared with wakefulness in men and women. However, when present, the phenomena are enhanced in individuals with OSA. The AHI data indicate that, under the prevailing experimental conditions, vLTF did not serve to mitigate apnea severity.

Effect of breathing oxygen-enriched air on exercise performance in patients with precapillary pulmonary hypertension: randomized, sham-controlled cross-over trial.

PubMed

Ulrich, Silvia; Hasler, Elisabeth D; Saxer, Stéphanie; Furian, Michael; Müller-Mottet, Séverine; Keusch, Stephan; Bloch, Konrad E

2017-04-14

The purpose of the current trial was to test the hypothesis that breathing oxygen-enriched air increases exercise performance of patients with pulmonary arterial or chronic thrombo-embolic pulmonary hypertension (PAH/CTEPH) and to investigate involved mechanisms. Twenty-two patients with PAH/CTEPH, eight women, means ± SD 61 ± 14 years, resting mPAP 35 ± 9mmHg, PaO2 ambient air >7.3 kPa, underwent four bicycle ergospirometries to exhaustion on different days, while breathing oxygen-enriched (FiO2 0.50, hyperoxia) or ambient air (FiO2 0.21, normoxia) using progressively increased or constant load protocols (with 75% maximal work rate under FiO2 0.21), according to a randomized, sham-controlled, single-blind, cross-over design. ECG, pulmonary gas-exchange, arterial blood gases, cerebral and quadriceps muscle tissue oxygenation (CTO and QMTO) by near-infrared spectroscopy were measured. In ramp exercise, maximal work rate increased from 113 ± 38 W with normoxia to 132 ± 48 W with hyperoxia, mean difference 19.7 (95% CI 10.5-28.9) W, P < 0.001. Constant load exercise endurance increased from 571 ± 443 to 1242 ± 514 s, mean difference 671 (95% CI 392-951) s, P < 0.001. At end-exercise with hyperoxia PaO2, CTO, QMTO, and PaCO2 were increased, and ventilatory equivalents for CO2 were reduced while the physiological dead space/tidal volume ratio remained unchanged. In patients with PAH/CTEPH, breathing oxygen-enriched air provides major increases in exercise performance. This is related to an improved arterial oxygenation that promotes oxygen availability in muscles and brain and to a reduction of the excessive ventilatory response to exercise thereby enhancing ventilatory efficiency. Patients with PAH/CTEPH may therefore benefit from oxygen therapy during daily physical activities and training. clinicaltrials.gov Identifier: NCT01748474. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

The impact of arousal state, sex, and sleep apnea on the magnitude of progressive augmentation and ventilatory long-term facilitation

PubMed Central

Syed, Ziauddin; Lin, Ho-Sheng

2013-01-01

We examined the impact of arousal state, sex, and obstructive sleep apnea (OSA) on the magnitude of progressive augmentation of the hypoxic ventilatory response and ventilatory long-term facilitation (vLTF). We also examined whether exposure to intermittent hypoxia during sleep has an impact on the apnea-hypopnea index (AHI) in individuals with OSA. Ten men and seven women with OSA, along with ten healthy men and ten healthy women, were exposed to twelve 2-min episodes of hypoxia (end-tidal Po2: 50 Torr) in the presence of sustained hypercapnia (end-tidal Pco2: 3 Torr above baseline), followed by a 30-min recovery period during wakefulness and sleep. The OSA participants completed an additional sham study during sleep. The AHI during the first hour of sleep following the intermittent hypoxia and sham protocols were compared. Progressive augmentation was only evident during wakefulness and was enhanced in the OSA participants. vLTF was evident during wakefulness and sleep. When standardized to baseline, vLTF was greater during wakefulness and was enhanced in the OSA group (men: wakefulness 1.39 ± 0.08 vs. sleep 1.14 ± 0.03; women: wakefulness 1.35 ± 0.03 vs. sleep 1.16 ± 0.05 fraction of baseline; P ≤ 0.001) compared with control (men: wakefulness 1.19 ± 0.03 vs. sleep 1.09 ± 0.03; women: wakefulness 1.26 ± 0.05 vs. sleep 1.08 ± 0.04 fraction of baseline; P ≤ 0.001). The AHI following exposure to intermittent hypoxia was increased (intermittent hypoxia 72.8 ± 7.3 vs. sham 56.5 ± 7.0 events/h; P ≤ 0.01). Sex-related differences were not observed for the primary measures. We conclude that progressive augmentation is not evident, and the magnitude of vLTF is diminished during sleep compared with wakefulness in men and women. However, when present, the phenomena are enhanced in individuals with OSA. The AHI data indicate that, under the prevailing experimental conditions, vLTF did not serve to mitigate apnea severity. PMID:23139361

High-frequency oscillatory ventilation in ALI/ARDS.

PubMed

Ali, Sammy; Ferguson, Niall D

2011-07-01

In the last 2 decades, our goals for mechanical ventilatory support in patients with acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) have changed dramatically. Several randomized controlled trials have built on a substantial body of preclinical work to demonstrate that the way in which we employ mechanical ventilation has an impact on important patient outcomes. Avoiding ventilator-induced lung injury (VILI) is now a major focus when clinicians are considering which ventilatory strategy to employ in patients with ALI/ARDS. Physicians are searching for methods that may further limit VILI, while still achieving adequate gas exchange. Copyright © 2011 Elsevier Inc. All rights reserved.

[A case of emergency surgery in a patient with bronchial asthma under continuous spinal anesthesia].

PubMed

Noda, Keiichi; Ryo, Kenshu; Nakamoto, Ai

2003-10-01

A 78-year-old male, observed for bronchial asthma, underwent two emergency operations within eight days. The first operation was performed under general anesthesia with tracheal intubation. Anesthesia was maintained by sevoflurane-oxygen and continuous infusion of propofol in combination with epidural injection of lidocaine. During the operation, respiratory sound was almost clear. But wheezing occurred as he awoke after discontinuation of the anesthetics. He needed ventilatory support for three days for status asthmatics. The second operation was performed under continuous spinal anesthesia using hypobaric tetracaine and hyperbaric bupivacaine. No ventilatory support was necessary after the operation and he was discharged uneventfully.

History of Mechanical Ventilation. From Vesalius to Ventilator-induced Lung Injury.

PubMed

Slutsky, Arthur S

2015-05-15

Mechanical ventilation is a life-saving therapy that catalyzed the development of modern intensive care units. The origins of modern mechanical ventilation can be traced back about five centuries to the seminal work of Andreas Vesalius. This article is a short history of mechanical ventilation, tracing its origins over the centuries to the present day. One of the great advances in ventilatory support over the past few decades has been the development of lung-protective ventilatory strategies, based on our understanding of the iatrogenic consequences of mechanical ventilation such as ventilator-induced lung injury. These strategies have markedly improved clinical outcomes in patients with respiratory failure.

Ventilatory support in critically ill hematology patients with respiratory failure

PubMed Central

2012-01-01

Introduction Hematology patients admitted to the ICU frequently experience respiratory failure and require mechanical ventilation. Noninvasive mechanical ventilation (NIMV) may decrease the risk of intubation, but NIMV failure poses its own risks. Methods To establish the impact of ventilatory management and NIMV failure on outcome, data from a prospective, multicenter, observational study were analyzed. All hematology patients admitted to one of the 34 participating ICUs in a 17-month period were followed up. Data on demographics, diagnosis, severity, organ failure, and supportive therapies were recorded. A logistic regression analysis was done to evaluate the risk factors associated with death and NIVM failure. Results Of 450 patients, 300 required ventilatory support. A diagnosis of congestive heart failure and the initial use of NIMV significantly improved survival, whereas APACHE II score, allogeneic transplantation, and NIMV failure increased the risk of death. The risk factors associated with NIMV success were age, congestive heart failure, and bacteremia. Patients with NIMV failure experienced a more severe respiratory impairment than did those electively intubated. Conclusions NIMV improves the outcome of hematology patients with respiratory insufficiency, but NIMV failure may have the opposite effect. A careful selection of patients with rapidly reversible causes of respiratory failure may increase NIMV success. PMID:22827955

Ventilatory Patterning in a Mouse Model of Stroke

PubMed Central

Koo, Brian B; Strohl, Kingman P; Gillombardo, Carl B; Jacono, Frank J

2010-01-01

Cheyne-Stokes respiration (CSR) is a breathing pattern characterized by waxing and waning of breath volume and frequency, and is often recognized following stroke, when causal pathways are often obscure. We used an animal model to address the hypothesis that cerebral infarction is a mechanism for producing breathing instability. Fourteen male A/J mice underwent either stroke (n=7) or sham (n=7) procedure. Ventilation was measured using whole body plethysmography. Respiratory rate (RR), tidal volume (VT) and minute ventilation (Ve) mean values and coefficient of variation were computed for ventilation and oscillatory behavior. In addition, the ventilatory data were computationally fit to models to quantify autocorrelation, mutual information, sample entropy and a nonlinear complexity index. At the same time post procedure, stroke when compared to sham animal breathing consisted of a lower RR and autocorrelation, higher coefficient of variation for VT and higher coefficient of variation for Ve. Mutual information and the nonlinear complexity index were higher in breathing following stroke which also demonstrated a waxing/waning pattern. The absence of stroke in the sham animals was verified anatomically. We conclude that ventilatory pattern following cerebral infarction demonstrated increased variability with increased nonlinear patterning and a waxing/waning pattern, consistent with CSR. PMID:20472101

Recent advances on the functional and evolutionary morphology of the amniote respiratory apparatus.

PubMed

Lambertz, Markus

2016-02-01

Increased organismic complexity in metazoans was achieved via the specialization of certain parts of the body involved in different faculties (structure-function complexes). One of the most basic metabolic demands of animals in general is a sufficient supply of all tissues with oxygen. Specialized structures for gas exchange (and transport) consequently evolved many times and in great variety among bilaterians. This review focuses on some of the latest advancements that morphological research has added to our understanding of how the respiratory apparatus of the primarily terrestrial vertebrates (amniotes) works and how it evolved. Two main components of the respiratory apparatus, the lungs as the "exchanger" and the ventilatory apparatus as the "active pump," are the focus of this paper. Specific questions related to the exchanger concern the structure of the lungs of the first amniotes and the efficiency of structurally simple snake lungs in health and disease, as well as secondary functions of the lungs in heat exchange during the evolution of sauropod dinosaurs. With regard to the active pump, I discuss how the unique ventilatory mechanism of turtles evolved and how understanding the avian ventilatory strategy affects animal welfare issues in the poultry industry. © 2016 New York Academy of Sciences.

Periodic breathing and oxygen supplementation in Chilean miners at high altitude (4200m).

PubMed

Moraga, Fernando A; Jiménez, Daniel; Richalet, Jean Paul; Vargas, Manuel; Osorio, Jorge

2014-11-01

Our objective was to determine the nocturnal ventilatory pattern and characterize the effect of oxygen enrichment on nocturnal ventilatory pattern and sleep quality in miners exposed to intermittent hypobaric hypoxia at 4200m. A total of 16 acclimatized miners were studied. Nocturnal ventilatory pattern (plethysmographic inductance), arterial oxygen saturation and heart rate (pulse oximetry) were performed in 9/16 subjects. Sleep quality at high altitude was assessed by self-questionnaires in 16/16 subjects. All measurements were performed during at least 7h of sleep. Subjects were studied while sleeping at high altitude without (control, C) and with oxygen supplementation (FiO2=0.25, treated, T). Periodic breathing (%) C: 25±18 vs T: 6.6±5.6 (p<0.05), apneas index (no./h) C: 34.9±24.1 vs T: 8.5±6.8 (p<0.05); and sleep quality C: 17.8±3.4 vs T: 12.1±2.2 (p<0.0001) were evaluated. In conclusion, periodic breathing with apneas was present in miners exposed to high altitude for 1 to 4 years and was reduced by treatment with supplementary oxygen. Copyright © 2014 Elsevier B.V. All rights reserved.

Bronchitis in men employed in the coke industry

PubMed Central

Walker, D. D.; Archibald, R. M.; Attfield, M. D.

1971-01-01

Walker, D. D., Archibald, R. M., and Attfield, M. D. (1971).Brit. J. industr. Med.,28, 358-363. Bronchitis in men employed in the coke industry. An epidemiological survey to determine the prevalence of bronchitis in men employed at two of the National Coal Board's coking plants is described. Eight hundred and eighty-one men (91%) of the total working population were examined. A strong association was found between bronchitis prevalence and cigarette smoking (P < 0·001). In addition, men who smoked and who were exposed to high temperatures, dust, and fumes in the environment of the coke-ovens had more bronchitis than men who worked elsewhere in the cokeworks (P < 0·02). Both the presence of bronchitis and employment in the environment of the coke-ovens had significant and independent effects on ventilatory capacity. The combination of cigarette smoking and previous employment in a dusty industry also had a significant effect on ventilatory capacity. The investigation suggests that cigarette smoking, and the combination of smoking and pollution from the coke-ovens and previous occupation, appear to be important factors in the aetiology of bronchitis and reduced ventilatory capacity in men employed in the coke manufacturing industry. PMID:5124835

Reducing the Indication for Ventilatory Support in the Severely Burned Patient: Results of a New Protocol Approach at a Regional Burn Center.

PubMed

Gille, Jochen; Bauer, Nicole; Malcharek, Michael J; Dragu, Adrian; Sablotzki, Armin; Taha, Hischam; Czeslick, Elke

2016-01-01

Initial management of the severely injured routinely includes sedation and mechanical ventilatory support. However, nonjudiciously applied mechanical ventilatory support can itself lead to poorer patient outcomes. In an attempt to reduce this iatrogenic risk, a standardized, in-house, five-point protocol providing clinical guidance on the use and duration of ventilation was introduced and analyzed, and the impact on patient outcomes was assessed. In 2007, a protocol for early spontaneous breathing was introduced and established in clinical practice. This protocol included: 1) early extubation (≤6 hours after admission) in the absence of absolute ventilatory indication; 2) avoidance of "routine intubation" in spontaneously breathing patients; 3) early postoperative extubation, including patients requiring multiple surgical interventions; 4) intensive chest and respiratory physiotherapy with routine application of expectorants; and 5) early active mobilization. A retrospective clinical study compared patients (group A) over a 2-year period admitted under the new protocol with a historical patient group (group B). Patients in group A (n = 38) had fewer ventilator days over the time-course of treatment (3 [1; 5.8] vs 18.5 days [0.5; 20.5]; P = .0001) with a lower rate of tracheostomies (15.8 vs 54%; P = .0003). Patients on ventilation at admission in group A had shorter ventilation periods after admission (4.75 [4; 22.25] vs 378 hours [8.5; 681.5]; P = .0003), and 66.7% of these patients were extubated within 6 hours of admission (vs 9.1% in group B). No patients fulfilling the inclusion criteria required re- or emergency intubation. In the first 5 days of treatment, significantly lower Sequential Organ Failure Assessment scores were recorded in group A. There was also a trend for lower mortality rates (0 [0%] vs 6 [14%]), sepsis rates (24 [63.2%] vs 37 [88.1%]), and cumulative fluid balance on days 3 and 7 in group A. In contrast, group A demonstrated an elevated rate of pneumonia (15 [39.5%] vs 8 [19%]). These trends, however, lacked statistical significance. Our five-point protocol was safe and easily translated into clinical practice. In the authors experience, this protocol significantly reduced the ventilatory period in severely injured. Furthermore, this study suggests that many injured may be over-treated with routine ventilation, which carries accompanying risks.

Lipopolysaccharide-induced carotid body inflammation in cats: functional manifestations, histopathology and involvement of tumour necrosis factor-alpha.

PubMed

Fernández, Ricardo; González, Sergio; Rey, Sergio; Cortés, Paula P; Maisey, Kevin R; Reyes, Edison-Pablo; Larraín, Carolina; Zapata, Patricio

2008-07-01

In the absence of information on functional manifestations of carotid body (CB) inflammation, we studied an experimental model in which lipopolysaccharide (LPS) administration to pentobarbitone-anaesthetized cats was performed by topical application upon the CB surface or by intravenous infusion (endotoxaemia). The latter caused: (i) disorganization of CB glomoids, increased connective tissue, and rapid recruitment of polymorphonuclear cells into the vascular bed and parenchyma within 4 h; (ii) increased respiratory frequency and diminished ventilatory chemoreflex responses to brief hypoxia (breathing 100% N(2) for 10 s) and diminished ventilatory chemosensory drive (assessed by 100% O(2) tests) during normoxia and hypoxia; (iii) tachycardia, increased haematocrit and systemic hypotension in response to LPS i.v.; and (iv) increased basal frequency of carotid chemosensory discharges during normoxia, but no change in maximal chemoreceptor responses to brief hypoxic exposures. Lipopolysaccharide-induced tachypnoea was prevented by prior bilateral carotid neurotomy. Apoptosis was not observed in CBs from cats subjected to endotoxaemia. Searching for pro-inflammatory mediators, tumour necrosis factor-alpha (TNF-alpha) was localized by immunohistochemistry in glomus and endothelial cells; reverse transcriptase-polymerase chain reaction revealed that the CB expresses the mRNAs for both type-1 (TNF-R1) and type-2 TNF-alpha receptors (TNF-R2); Western blot confirmed a band of the size expected for TNF-R1; and histochemistry showed the presence of TNF-R1 in glomus cells and of TNF-R2 in endothelial cells. Experiments in vitro showed that the frequency of carotid nerve discharges recorded from CBs perfused and superfused under normoxic conditions was not significantly modified by TNF-alpha, but that the enhanced frequency of chemosensory discharges recorded along responses to hypoxic stimulation was transiently diminished in a dose-dependent manner by TNF-alpha injections. The results suggest that the CB may operate as a sensor for immune signals, that the CB exhibits histological features of acute inflammation induced by LPS, that TNF-alpha may participate in LPS-induced changes in chemosensory activity and that some pathophysiological reactions to high levels of LPS in the bloodstream may originate from changes in CB function.