Effect of theophylline and dipyridamole on the respiratory response to isocapnic hypoxia in normal human subjects

1991 ◽  
Vol 80 (2) ◽  
pp. 107-112 ◽  
Author(s):  
S. T. Parsons ◽  
T. L. Griffiths ◽  
J. M. L. Christie ◽  
S. T. Holgate
Keyword(s):  
Oxygen Saturation ◽  
Maximum Rate ◽  
Human Subjects ◽  
Minute Ventilation ◽  
Physiological Role ◽  
Respiratory Control ◽  
Inspiratory Pressure ◽  
Respiratory Response ◽  
Peripheral Chemoreceptor ◽  
Pressure Development

1. Twelve healthy young men took part in this investigation of the effect of oral theophylline and dipyridamole (two drugs known to affect the pharmacological effects of the purine nucleoside adenosine) on the respiratory response to isocapnic hypoxia. 2. The subjects underwent hypoxic rebreathing manoeuvres after 3-day pretreatments with each of the drugs for 12 h and were at least 2 h postprandial. For each in-Minute ventilation, the maximum rate of isometric inspiratory pressure development at the mouth and the ratio of inspiratory duration to total breath duration were analysed breath-by-breath and regressions of these variables upon the haemoglobin oxygen saturation were performed. 3. The slopes and intercepts of the lines describing the relationships of minute ventilation and the maximum rate of isometric inspiratory pressure development at the mouth with haemoglobin oxygen saturation were unaffected by the study drugs, and no differences in the pattern of breathing were observed. 4. We conclude that oral administration of these drugs does not result in alteration of the response of the respiratory system to progressive isocapnic hypoxia. 5. This suggests that either adenosine has no physiological role in hypoxic respiratory control as measured, or that it has opposing peripheral chemoreceptor and central respiratory centre effects which could not be distinguished by the techniques used.

Ventilatory response to transient hyperoxia in head injury hyperventilation

1980 ◽  
Vol 49 (1) ◽  
pp. 52-58 ◽  
Author(s):  
A. G. Leitch ◽  
J. E. McLennan ◽  
S. Balkenhol ◽  
R. L. McLaurin ◽  
R. G. Loudon
Keyword(s):  
Head Injury ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Normal Subjects ◽  
Respiratory Alkalosis ◽  
Cerebral Injury ◽  
Peripheral Chemoreceptor ◽  
Male Patients ◽  
Almost All

We have measured breath-by-breath instantaneous minute ventilation (VIinst) before, during, and after the administration of 10 breaths of 100% oxygen to seven male patients with head injury hyperventilation. The patients were hypoxemic (PaO2 61.2 ± 6.3) and hypocapnic (PaCO2 26.6 ± 5.9) with a respiratory alkalosis (pH 7.53 ± 0.06) while breathing air. Following the oxygen VIinst fell on the average by 40 ± 12.7% from 16.06 ± 3.75 1.min-1 to a minimum of 9.73 ± 3.20 1.min-1 at 20.4 ± 2.9 s after the first breath of oxygen. In the majority of our hyperventilating patients, almost all of the resting hyperventilation could be abolished transiently by 100% oxygen. This fall in ventilation represents the peripheral chemoreceptor contribution to resting ventilation and is increased in the head injury patients in comparison with normal subjects breathing air or hypoxic gas mixtures, altitude-acclimatized subjects and patients who are hypoxic because of chronic bronchitis or interstitial lung disease. We suggest that the increased reflex hypoxic drive to ventilation found in our patients is secondary to their cerebral injury, resulting in a reduction of descending cortical inhibitory influences on the medullary respiratory control centers.

Effect of Almitrine on Hypoxic Ventilatory Drive Measured by Transient and Progressive Isocapnic Hypoxia in Normal Men

1989 ◽  
Vol 77 (4) ◽  
pp. 431-437 ◽  
Author(s):  
M. A. A. Airlie ◽  
D. C. Flenley ◽  
P. M. Warren
Keyword(s):  
Oxygen Saturation ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen ◽  
Controlled Study ◽  
Peripheral Chemoreceptor ◽  
Ventilatory Drive ◽  
The Difference ◽  
Normal Men

1. In a double-blind placebo-controlled study, we have investigated the effect of the peripheral chemoreceptor stimulant drug almitrine bismesylate on hypoxic ventilatory drive (expressed as the slope of the minute ventilation/arterial oxygen saturation relationship in litres min−1 %−1) as measured by both progressive isocapnic hypoxia at rest and transient hypoxia (three breaths of 100% N2) during moderate exercise, in seven normal men, to determine if the ventilatory response to the transient hypoxic stimulus is a more specific measure of peripheral chemoreceptor sensitivity to hypoxia. 2. Hypoxic ventilatory drive measured using progressive isocapnic hypoxia ranged from −0.13 to −2.65 litres min−1 % −1 after placebo and from − 0.20 to − 6.48 litres min−1 %−1 after almitrine. The response was greater after almitrine in six of the seven subjects, and the difference was significant for the whole group (P < 0.05). 3. Hypoxic ventilatory drive measured using transient hypoxia ranged from −0.19 to −1.59 litres min−1 %−1 after placebo and from −0.09 to −1.62 litres min−1 %−1 after almitrine. The response was not consistently greater after almitrine, and the difference was not significant for the group. 4. Difficulties in accurately quantifying a brief rise in minute ventilation after transient hypoxia, particularly in subjects with a low hypoxic ventilatory drive, may have masked small changes in the slope of the minute ventilation/arterial oxygen saturation relationship with this method. However, the significant increase in the response to progressive isocapnic hypoxia after almitrine suggests that the failure to demonstrate an effect using transient hypoxic stimuli was not solely due to between-day variation in hypoxic ventilatory drive or the small numbers of subjects studied. 5. We conclude that, although transient hypoxia avoids any central depression of ventilation that might result from the prolonged hypoxia used in the conventional steady state or progressive isocapnic methods (thereby leading to underestimation of the hypoxic ventilatory drive), the ventilatory response to such transient stimuli is also affected by factors other than peripheral chemoreceptor activity.

Effect of caffeine on peripheral chemoreceptor activity in premature neonates: interaction with sleep stages

2004 ◽  
Vol 96 (6) ◽  
pp. 2161-2166 ◽  
Author(s):  
Karen Chardon ◽  
Véronique Bach ◽  
Frédéric Telliez ◽  
Virginie Cardot ◽  
Pierre Tourneux ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Sleep Stage ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Sleep Stages ◽  
Quiet Sleep ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Premature Neonates ◽  
Postconceptional Age

Caffeine is widely used for the treatment of apnea in premature neonates. However, the localization of caffeine's target site (central nervous system and/or peripheral chemoreceptors) is not well defined, especially for sleeping neonates whose sleep stages interact with respiratory control. The aim of this study was to assess the activity of the peripheral chemoreceptors in relation to sleep stages in premature neonates treated (or not) with caffeine for idiopathic apnea. Peripheral chemoreceptor activity was assessed in 22 neonates (postconceptional age of 36 ± 1 wk with birth weights ranging from 790 to 1,910 g) by performing a 30-s hyperoxic test during active and quiet sleep. Eleven neonates received caffeine treatment (4.0 ± 0.5 mg·kg-1·day-1) and 11 served as controls. For all neonates, the decrease in minute ventilation observed during hyperoxia was greater during active than during quiet sleep. Neonates receiving caffeine showed a significantly greater decrease in ventilation during hyperoxia in both sleep stages, compared with controls (caffeine; -29.7 ± 12.8% vs. control; -22.0 ± 7.4%; F1,15 = 4.6, P = 0.04). We conclude that caffeine administration increases the effectiveness of chemoreceptor activity. Because sleep stage durations were not affected by the treatment, it is likely that the decrease in apneic episodes typically observed with caffeine therapy is only related to respiratory processes and is independent of the sleep stage organization.

Effect of Age on Oxygen-Binding in Normal Human Subjects

1976 ◽  
Vol 51 (2) ◽  
pp. 185-188
Author(s):  
P. M. Tweeddale ◽  
R. J. E. Leggett ◽  
D. C. Flenley
Keyword(s):  
Oxygen Saturation ◽  
Oxygen Tension ◽  
Inorganic Phosphate ◽  
Human Subjects ◽  
Oxygen Binding ◽  
Corpuscular Haemoglobin ◽  
Positive Correlation ◽  
Normal Human ◽  
Mean Corpuscular Haemoglobin ◽  
Effect Of Age

1. Oxygen-binding, plasma and intra-erythrocytic pH, and haemoglobin, 2,3-diphosphoglycerate and inorganic phosphate concentrations were measured in sixty-two healthy non-smokers aged between 18 and 89 years. 2. P50 (oxygen tension at 50% oxygen saturation) expressed at plasma pH 7·40 and Pco2 5·33 kPa showed a positive correlation with age. 3. This correlation of P50 with age was closer when P50 was expressed at a constant intra-erythrocytic pH 7·20. On average P50 at intra-erythrocytic pH 7·20 increased from 3·59 kPa at 20 years to 3·96 kPa at 90 years of age. 4. 2,3-Diphosphoglycerate, inorganic phosphate, haemoglobin and mean corpuscular haemoglobin concentrations did not correlate with P50 or with age.

Clock gene-independent daily regulation of haemoglobin oxidation in red blood cells

2021 ◽  
Author(s):  
Andrew D. Beale ◽  
Priya Crosby ◽  
Utham K. Valekunja ◽  
Rachel S. Edgar ◽  
Johanna E. Chesham ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Human Subjects ◽  
Developmental Regulation ◽  
Physiological Role ◽  
Cell Types ◽  
The Body

AbstractCellular circadian rhythms confer daily temporal organisation upon behaviour and physiology that is fundamental to human health and disease. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body. Being naturally anucleate, RBC circadian rhythms share key elements of post-translational, but not transcriptional, regulation with other cell types. The physiological function and developmental regulation of RBC circadian rhythms is poorly understood, however, partly due to the small number of appropriate techniques available. Here, we extend the RBC circadian toolkit with a novel biochemical assay for haemoglobin oxidation status, termed “Bloody Blotting”. Our approach relies on a redox-sensitive covalent haem-haemoglobin linkage that forms during cell lysis. Formation of this linkage exhibits daily rhythms in vitro, which are unaffected by mutations that affect the timing of circadian rhythms in nucleated cells. In vivo, haemoglobin oxidation rhythms demonstrate daily variation in the oxygen-carrying and nitrite reductase capacity of the blood, and are seen in human subjects under controlled laboratory conditions as well as in freely-behaving humans. These results extend our molecular understanding of RBC circadian rhythms and suggest they serve an important physiological role in gas transport.

Pathophysiology of genetic deficiency in tissue kallikrein activity in mouse and man

2013 ◽  
Vol 110 (09) ◽  
pp. 476-483 ◽  
Author(s):  
Ludovic Waecke ◽  
Louis Potier ◽  
Christine Richer ◽  
Ronan Roussel ◽  
Nadine Bouby ◽  
...  
Keyword(s):  
Human Subjects ◽  
Physiological Role ◽  
Tissue Kallikrein ◽  
Site Mutation ◽  
Cardiac Ischaemia ◽  
Kinin Receptors ◽  
At1 Receptor Antagonists ◽  
Kallikrein Activity ◽  
Deficient Mice

SummaryStudy of mice rendered deficient in tissue kallikrein (TK) by gene inactivation and human subjects partially deficient in TK activity as consequence of an active site mutation has allowed recognising the physiological role of TK and its peptide products kinins in arterial function and in vasodilatation, in both species. TK appears as the major kinin forming enzyme in arteries, heart and kidney. Non-kinin mediated actions of TK may occur in epithelial cells in the renal tubule. In basal condition, TK deficiency induces mild defective phenotypes in the cardiovascular system and the kidney. However, in pathological situations where TK synthesis is typically increased and kinins are produced, TK deficiency has major, deleterious consequences. This has been well documented experimentally for cardiac ischaemia, diabetes renal disease, peripheral ischaemia and aldosterone-salt induced hypertension. These conditions are all aggravated by TK deficiency. The beneficial effect of ACE/kininase II inhibitors or angiotensin II AT1 receptor antagonists in cardiac ischaemia is abolished in TK-deficient mice, suggesting a prominent role for TK and kinins in the cardioprotective action of these drugs. Based on findings made in TK-deficient mice and additional evidence obtained by pharmacological or genetic inactivation of kinin receptors, development of novel therapeutic approaches relying on kinin receptor agonism may be warranted.

Effect of transcendental meditation on breathing and respiratory control

1984 ◽  
Vol 56 (3) ◽  
pp. 607-612 ◽  
Author(s):  
N. Wolkove ◽  
H. Kreisman ◽  
D. Darragh ◽  
C. Cohen ◽  
H. Frank
Keyword(s):  
Transcendental Meditation ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Respiratory Pattern ◽  
Quiet Breathing ◽  
The Unconscious ◽  
Eyes Closed ◽  
Significant Difference ◽  
Regulation Of Breathing ◽  
Eyes Open

We studied the effect of transcendental meditation (TM) on breathing using 16 experienced meditators and 16 control subjects. In controls, there was no significant difference in minute ventilation (VE), respiratory pattern, or hypercapnic response, whether breathing with eyes open-awake (CA), or with eyes closed-relaxing (CR). In meditators, VE decreased significantly during quiet breathing from 14.0 +/- 0.7 1/min with eyes open-awake (MA) to 12.4 +/- 0.6 1/min during meditation (MM) (P less than 0.02). The change in VE during meditation was due to a decrease in tidal volume (VT) resulting from a shortened inspiratory time (TI). Meditation was associated with a decreased response to progressive hypercapnia from 3.7 +/- 0.4 to 2.5 +/- 0.21 X min-1 X Torr-1 during MA and MM trials, respectively (P less than 0.01). During meditation VT was smaller at a given alveolar PCO2 than during MA studies because of a decrease in mean inspiratory flow rate (VT/TI). These observations suggest that an alteration in wakefulness, more subtle than sleep or the unconscious state, can significantly affect the chemical and neural regulation of breathing.

Peripheral chemoreceptor function in children with the congenital central hypoventilation syndrome

1993 ◽  
Vol 74 (1) ◽  
pp. 379-387 ◽  
Author(s):  
D. Gozal ◽  
C. L. Marcus ◽  
D. Shoseyov ◽  
T. G. Keens
Keyword(s):  
Vital Capacity ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Clinical Manifestations ◽  
Congenital Central Hypoventilation Syndrome ◽  
Tidal Breathing ◽  
Peripheral Chemoreceptor ◽  
Ventilatory Responses ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome

In children with the congenital central hypoventilation syndrome (CCHS), some patients require mechanical ventilation during sleep, whereas others need respiratory assistance even when awake. The cause of this disparity is unclear. We hypothesized that differences in peripheral chemoreceptor response (PCR) could provide an explanatory mechanism for this disparity in clinical manifestations. PCR was measured in five children with CCHS and five sex- and age-matched controls by measuring the ventilatory responses induced by 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 5% and 15% CO2 in O2 and 5% CO2–95% N2. Tidal breathing of 100% O2 resulted in similar ventilatory responses in CCHS patients and controls with various changes dependent on the method of analysis of response used. Acute hypoxia by N2 tidal breathing resulted in a 39.2 +/- 22% increase in respiratory rate in CCHS patients and a 15.1 +/- 11.1% increase in controls (P < 0.05), with similar increases in minute ventilation (VE) of 124 +/- 69% and 85 +/- 11%, respectively. Vital capacity breaths of each of the CO2-containing gas mixtures induced similar increases in VE in CCHS patients and controls. The changes in VE obtained with 15% CO2–85% O2 and with 5% CO2–95% N2 were significantly greater than those with 5% CO2–95% O2, suggesting a dose-dependent response as well as additive effects of hypercapnic and hypoxic stimuli. We conclude that the PCR, when assessed by acute hypoxia, hyperoxia, or hypercapnia, is present and intact in CCHS children who are able to sustain adequate ventilation during wakefulness.(ABSTRACT TRUNCATED AT 250 WORDS)

Living high-training low increases hypoxic ventilatory response of well-trained endurance athletes

2002 ◽  
Vol 93 (4) ◽  
pp. 1498-1505 ◽  
Author(s):  
Nathan E. Townsend ◽  
Christopher J. Gore ◽  
Allan G. Hahn ◽  
Michael J. McKenna ◽  
Robert J. Aughey ◽  
...  
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Endurance Athletes ◽  
Hypoxic Exposure ◽  
Dependent Manner ◽  
Hypoxic Ventilatory Response ◽  
Ambient Conditions ◽  
Altitude Exposure ◽  
End Tidal

This study determined whether “living high-training low” (LHTL)-simulated altitude exposure increased the hypoxic ventilatory response (HVR) in well-trained endurance athletes. Thirty-three cyclists/triathletes were divided into three groups: 20 consecutive nights of hypoxic exposure (LHTLc, n = 12), 20 nights of intermittent hypoxic exposure (four 5-night blocks of hypoxia, each interspersed with 2 nights of normoxia, LHTLi, n = 10), or control (Con, n = 11). LHTLc and LHTLi slept 8–10 h/day overnight in normobaric hypoxia (∼2,650 m); Con slept under ambient conditions (600 m). Resting, isocapnic HVR (ΔV˙e/ΔSpO2 , whereV˙e is minute ventilation and SpO2 is blood O2 saturation) was measured in normoxia before hypoxia (Pre), after 1, 3, 10, and 15 nights of exposure (N1, N3, N10, and N15, respectively), and 2 nights after the exposure night 20 (Post). Before each HVR test, end-tidal Pco 2(Pet CO2 ) and V˙e were measured during room air breathing at rest. HVR (l · min−1 · %−1) was higher ( P < 0.05) in LHTLc than in Con at N1 (0.56 ± 0.32 vs. 0.28 ± 0.16), N3 (0.69 ± 0.30 vs. 0.36 ± 0.24), N10 (0.79 ± 0.36 vs. 0.34 ± 0.14), N15 (1.00 ± 0.38 vs. 0.36 ± 0.23), and Post (0.79 ± 0.37 vs. 0.36 ± 0.26). HVR at N15 was higher ( P < 0.05) in LHTLi (0.67 ± 0.33) than in Con and in LHTLc than in LHTLi. Pet CO2 was depressed in LHTLc and LHTLi compared with Con at all points after hypoxia ( P < 0.05). No significant differences were observed for V˙e at any point. We conclude that LHTL increases HVR in endurance athletes in a time-dependent manner and decreases Pet CO2 in normoxia, without change inV˙e. Thus endurance athletes sleeping in mild hypoxia may experience changes to the respiratory control system.

Manipulation of central blood volume and implications for respiratory control function

2014 ◽  
Vol 306 (12) ◽  
pp. H1669-H1678 ◽  
Author(s):  
Tadayoshi Miyamoto ◽  
Damian Miles Bailey ◽  
Hidehiro Nakahara ◽  
Shinya Ueda ◽  
Masashi Inagaki ◽  
...  
Keyword(s):  
Blood Volume ◽  
Lower Body Negative Pressure ◽  
Control Function ◽  
Minute Ventilation ◽  
Water Immersion ◽  
Respiratory Control ◽  
Intersection Point ◽  
Operating Point ◽  
Central Blood Volume ◽  
End Tidal

The respiratory operating point (ventilatory or arterial Pco2 response) is determined by the intersection point between the controller and plant subsystem elements within the respiratory control system. However, to what extent changes in central blood volume (CBV) influence these two elements and the corresponding implications for the respiratory operating point remain unclear. To examine this, 17 apparently healthy male participants were exposed to water immersion (WI) or lower body negative pressure (LBNP) challenges to manipulate CBV and determine the corresponding changes. The respiratory controller was characterized by determining the linear relationship between end-tidal Pco2 (PetCO2) and minute ventilation (V̇e) [V̇e = S × (PetCO2 − B)], whereas the plant was determined by the hyperbolic relationship between V̇e and PetCO2 (PetCO2 = A/V̇e + C). Changes in V̇e at the operating point were not observed under either WI or LBNP conditions despite altered PetCO2 ( P < 0.01), indicating a moving respiratory operating point. An increase (WI) and a decrease (LBNP) in CBV were shown to reset the controller element (PetCO2 intercept B) rightward and leftward, respectively ( P < 0.05), without any change in S, whereas the plant curve remained unaltered at the operating point. Collectively, these findings indicate that modification of the controller element rather than the plant element is the major factor that contributes toward an alteration of the respiratory operating point during CBV shifts.

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