scholarly journals Interleukin-1beta suppresses the ventilatory hypoxic response in rats via prostaglandin-dependent pathways

2017 ◽  
Vol 95 (6) ◽  
pp. 681-685 ◽  
Author(s):  
Nina P. Aleksandrova ◽  
Galina A. Danilova ◽  
Viacheslav G. Aleksandrov
Keyword(s):  
Ventilatory Response ◽  
Prostaglandin Synthesis ◽  
Respiratory Neurons ◽  
Hypoxic Ventilatory Response ◽  
Hypoxic Response ◽  
Interleukin 1Beta ◽  
Spontaneously Breathing ◽  
The Brain ◽  
Ventilatory Response To Hypoxia

We investigated the effect of the major inflammatory cytokine interleukin-1beta (IL-1β) on the ventilatory response to hypoxia. The goal was to test the hypothesis that IL-1β impairs the hypoxic ventilatory response in vivo by indirectly inhibiting respiratory neurons in the brainstem via prostaglandins. Thus, IL-1β was delivered by cerebroventricular injection, and the ventilatory hypoxic response was assessed in anesthetized, spontaneously breathing rats pretreated with or without diclofenac, a nonspecific inhibitor of prostaglandin synthesis. We found that the slope of the ventilatory response to hypoxia decreased almost 2-fold from 10.4 ± 3.02 to 4.06 ± 0.86 mL·min−1·(mm Hg)−1 (–61%) 90 min after administration of IL-1β (p < 0.05). The slope of tidal volume and mean inspiratory flow also decreased from 0.074 ± 0.02 to 0.039 ± 0.01 mL·(mm Hg)−1 (–45%, p < 0.05), and from 0.36 ± 0.07 to 0.2 ± 0.04 mL·s−1·(mm Hg)−1 (–46%, p < 0.05), respectively. Pretreatment with diclofenac blocked these effects. Thus, the data indicate that IL-1β degrades the ventilatory hypoxic response by stimulating production of prostaglandin. The increase of cerebral levels of IL-1β, which is induced by the activation of immune cells in the brain, may impair respiratory chemoreflexes.

scholarly journals Methodological and physiological variability within the ventilatory response to hypoxia in humans

2000 ◽  
Vol 88 (5) ◽  
pp. 1924-1932 ◽  
Author(s):  
Shu Zhang ◽  
Peter A. Robbins
Keyword(s):  
Coefficient Of Variation ◽  
Ventilatory Response ◽  
Systematic Variation ◽  
Hypoxic Ventilatory Response ◽  
Mean Values ◽  
Careful Choice ◽  
Physiological Variability ◽  
Coefficients Of Variation ◽  
Ventilatory Response To Hypoxia ◽  
Over Time

Measurement of the acute hypoxic ventilatory response (AHVR) requires careful choice of the hypoxic stimulus. If the stimulus is too brief, the response may be incomplete; if the stimulus is too long, hypoxic ventilatory depression may ensue. The purpose of this study was to compare three different techniques for assessing AHVR, using different hypoxic stimuli, and also to examine the between-day variability in AHVR. Ten subjects were studied, each on six different occasions, which were ≥1 wk apart. On each occasion, AHVR was assessed using three different protocols: 1) protocol SW, which uses square waves of hypoxia; 2) protocol IS, which uses incremental steps of hypoxia; and 3) protocol RB, which simulates an isocapnic rebreathing test. Mean values for hypoxic sensitivity were 1.02 ± 0.48, 1.15 ± 0.55, and 0.93 ± 0.60 (SD) l ⋅ min− 1 ⋅ %− 1for protocols SW, IS, and RB, respectively. These differed significantly ( P < 0.01). The coefficients of variation for measurement of AHVR were 20, 23, and 36% for the three protocols, respectively. These were not significantly different. There was a significant physiological variation in AHVR ( F 50,100 = 3.9, P < 0.001), with a coefficient of variation of 26%. We conclude that there was relatively little systematic variation between the three protocols but that AHVR varies physiologically over time.

Hypoxic-hypercapnic interaction in subjects with bilateral cerebral dysfunction

1963 ◽  
Vol 18 (6) ◽  
pp. 1139-1145 ◽  
Author(s):  
Fred Plum ◽  
Harold W. Brown
Keyword(s):  
Carbon Dioxide ◽  
Brain Damage ◽  
Pyramidal Tract ◽  
Ventilatory Response ◽  
Cerebral Dysfunction ◽  
Tract Disease ◽  
The Brain ◽  
Carbon Dioxide Response ◽  
Ventilatory Response To Hypoxia ◽  
Respiratory Responses

To analyze cerebral influences modifying autonomic respiratory responses, we compared normals and patients with bilateral pyramidal tract disease for their ventilatory response to hypoxia and hypoxia-hypercapnia. During eucapnia, the two groups showed similar hypoxic responses. During hypercapnia, the ventilatory response to hypoxia was greater in the brain-damaged subjects. This apparent augmentation, however, was due entirely to anoxia interacting with an abnormally facilitated carbon dioxide sensitivity: compared with normals, brain-damaged patients at PaOO2 90–100 mm Hg showed an 85% greater CO2 response, and at PaOO2 50 mm Hg showed a 79% greater CO2 response. Since cerebral dysfunction facilitated the ventilatory response to hypoxia-hypercapnia combined but not the response to hypoxia alone, the results imply that the two respiratory stimuli interact centrally rather than peripherally. respiration; brain damage; interaction; carbon dioxide response; forebrain effects; ventilation with CNS disease Submitted on February 18, 1963

Depression of hypoxic ventilatory response in humans by somatostatin

1988 ◽  
Vol 65 (3) ◽  
pp. 1050-1054 ◽  
Author(s):  
R. B. Filuk ◽  
D. J. Berezanski ◽  
N. R. Anthonisen
Keyword(s):  
Intravenous Infusion ◽  
Ventilatory Response ◽  
Normal Subjects ◽  
Small Decrease ◽  
Hypoxic Ventilatory Response ◽  
Arterial O2 Saturation ◽  
Ventilatory Response To Hypoxia

In nine normal subjects we measured the ventilatory response to isocapnic hypoxia with and without an intravenous infusion of 1 mg of somatostatin. Arterial O2 saturation was rapidly lowered to 80 +/- 2% in 2 min and maintained for 30 min. During control experiments, ventilation increased immediately (3-5 min) and then declined so that at 25 min of hypoxia ventilation was little above that in room air. Somatostatin was associated with a small decrease in ventilation while the subjects breathed room air. With hypoxia there was no immediate increase in ventilation for the group as a whole, although an increase was observed in one subject. With somatostatin, after 25 min of hypoxia, mean ventilation was lower than at any other time in the study; as hypoxia was discontinued ventilation increased slightly. Somatostatin causes profound depression of the ventilatory response to hypoxia by a mechanism that is not known but may be central. With somatostatin hypoxia of 25-min duration tends to depress ventilation.

Sex-dependent regulation of hypoxic ventilation in mice and humans is mediated by erythropoietin

2009 ◽  
Vol 296 (6) ◽  
pp. R1837-R1846 ◽  
Author(s):  
Jorge Soliz ◽  
Jonas Juhl Thomsen ◽  
Christophe Soulage ◽  
Carsten Lundby ◽  
Max Gassmann
Keyword(s):  
Ventilatory Response ◽  
Hypoxic Exposure ◽  
Hypoxic Ventilatory Response ◽  
Sexual Hormones ◽  
Female Mice ◽  
Knowing That ◽  
Human Volunteers ◽  
Respiratory Centers ◽  
The Brain ◽  
Transgenic Male

Acclimatization to hypoxic exposure relies on an elevated ventilation and erythropoietic activity. We recently proposed that erythropoietin (Epo) links both responses: apart from red blood cell production, cerebral and plasma Epo interact with the central and peripheral respiratory centers. Knowing that women cope better than men with reduced oxygen supply (as observed at high altitude), we analyzed the hypoxic ventilatory response in Epo-overexpressing transgenic male and female mice with high Epo levels in brain and plasma (Tg6) or in wild-type animals injected with recombinant human Epo (rhEpo). Exposure to moderate and severe hypoxia as well as to hyperoxia and injection of domperidone, a potent peripheral ventilatory stimulant, revealed that the presence of transgenic or rhEpo extensively increased the hypoxic ventilatory response in female mice compared with their corresponding male siblings. Alterations of catecholamines in the brain stem's respiratory centers were also sex dependent. In a proof-of-concept study, human volunteers were intravenously injected with 5,000 units rhEpo and subsequently exposed to 10% oxygen. Compared with men, the hypoxic ventilatory response was significantly increased in women. We conclude that Epo exerts a sex-dependent impact on hypoxic ventilation improving the response in female mice and in women that most probably involves sexual hormones. Our data provides an explanation as to why women are less susceptible to hypoxia-associated syndromes than men.

scholarly journals On the existence of a central respiratory oxygen sensor

2017 ◽  
Vol 123 (5) ◽  
pp. 1344-1349 ◽  
Author(s):  
Alexander V. Gourine ◽  
Gregory D. Funk
Keyword(s):  
Experimental Evidence ◽  
Oxygen Sensor ◽  
Ventilatory Response ◽  
Lung Ventilation ◽  
Partial Recovery ◽  
Hypoxic Ventilatory Response ◽  
Peripheral Chemoreceptor ◽  
Terrestrial Mammals

A commonly held view that dominates both the scientific and educational literature is that in terrestrial mammals the central nervous system lacks a physiological hypoxia sensor capable of triggering increases in lung ventilation in response to decreases in Po2 of the brain parenchyma. Indeed, a normocapnic hypoxic ventilatory response has never been observed in humans following bilateral resection of the carotid bodies. In contrast, almost complete or partial recovery of the hypoxic ventilatory response after denervation/removal of the peripheral respiratory oxygen chemoreceptors has been demonstrated in many experimental animals when assessed in an awake state. In this essay we review the experimental evidence obtained using in vitro and in vivo animal models, results of human studies, and discuss potential mechanisms underlying the effects of CNS hypoxia on breathing. We consider experimental limitations and discuss potential reasons why the recovery of the hypoxic ventilatory response has not been observed in humans. We review recent experimental evidence suggesting that the lower brain stem contains functional oxygen sensitive elements capable of stimulating respiratory activity independently of peripheral chemoreceptor input.

Somatostatin inhibits the ventilatory response to hypoxia in humans

1986 ◽  
Vol 60 (3) ◽  
pp. 997-1002 ◽  
Author(s):  
D. L. Maxwell ◽  
P. Chahal ◽  
K. B. Nolop ◽  
J. M. Hughes
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Open Circuit ◽  
Co2 Production ◽  
Adult Males ◽  
Hypoxic Response ◽  
Ventilatory Responses ◽  
End Tidal ◽  
Hypercapnic Response ◽  
Ventilatory Response To Hypoxia

The effects of a 90-min infusion of somatostatin (1 mg/h) on ventilation and the ventilatory responses to hypoxia and hypercapnia were studied in six normal adult males. Minute ventilation (VE) was measured with inductance plethysmography, arterial 02 saturation (SaO2) was measured with ear oximetry, and arterial PCO2 (Paco2) was estimated with a transcutaneous CO2 electrode. The steady-state ventilatory response to hypoxia (delta VE/delta SaO2) was measured in subjects breathing 10.5% O2 in an open circuit while isocapnia was maintained by the addition of CO2. The hypercapnic response (delta VE/delta PaCO2) was measured in subjects breathing first 5% and then 7.5% CO2 (in 52–55% O2). Somatostatin greatly attenuated the hypoxic response (control mean -790 ml x min-1.%SaO2 -1, somatostatin mean -120 ml x min-1.%SaO2 -1; P less than 0.01), caused a small fall in resting ventilation (mean % fall - 11%), but did not affect the hypercapnic response. In three of the subjects progressive ventilatory responses (using rebreathing techniques, dry gas meter, and end-tidal Pco2 analysis) and overall metabolism were measured. Somatostatin caused similar changes (mean fall in hypoxic response -73%; no change in hypercapnic response) and did not alter overall O2 consumption nor CO2 production. These results show an hitherto-unsuspected inhibitory potential of this neuropeptide on the control of breathing; the sparing of the hypercapnic response is suggestive of an action on the carotid body but does not exclude a central effect.

Influence of pregnancy on ventilatory and carotid body neural output responsiveness to hypoxia in cats

1989 ◽  
Vol 67 (2) ◽  
pp. 797-803 ◽  
Author(s):  
B. Hannhart ◽  
C. K. Pickett ◽  
J. V. Weil ◽  
L. G. Moore
Keyword(s):  
Carotid Body ◽  
Ventilatory Response ◽  
Hypoxic Ventilatory Response ◽  
Air Ventilation ◽  
Near Term ◽  
End Tidal ◽  
Neural Influences ◽  
End Tidal Co2 ◽  
Ventilatory Response To Hypoxia

Pregnancy increases ventilation and ventilatory sensitivity to hypoxia and hypercapnia. To determine the role of the carotid body in the increased hypoxic ventilatory response, we measured ventilation and carotid body neural output (CBNO) during progressive isocapnic hypoxia in 15 anesthetized near-term pregnant cats and 15 nonpregnant females. The pregnant compared with nonpregnant cats had greater room-air ventilation [1.48 +/- 0.24 vs. 0.45 +/- 0.05 (SE) l/min BTPS, P less than 0.01], O2 consumption (29 +/- 2 vs. 19 +/- 1 ml/min STPD, P less than 0.01), and lower end-tidal PCO2 (30 +/- 1 vs. 35 +/- 1 Torr, P less than 0.01). Lower end-tidal CO2 tensions were also observed in seven awake pregnant compared with seven awake nonpregnant cats (28 +/- 1 vs. 31 +/- 1 Torr, P less than 0.05). The ventilatory response to hypoxia as measured by the shape of parameter A was twofold greater (38 +/- 5 vs. 17 +/- 3, P less than 0.01) in the anesthetized pregnant compared with nonpregnant cats, and the CBNO response to hypoxia was also increased twofold (58 +/- 11 vs. 29 +/- 5, P less than 0.05). The increased CBNO response to hypoxia in the pregnant compared with the nonpregnant cats persisted after cutting the carotid sinus nerve while recording from the distal end, indicating that the increased hypoxic sensitivity was not due to descending central neural influences. We concluded that greater carotid body sensitivity to hypoxia contributed to the increased hypoxic ventilatory responsiveness observed in pregnant cats.

Interindividual variation in hypoxic ventilatory response: potential role of carotid body

1987 ◽  
Vol 63 (5) ◽  
pp. 1884-1889 ◽  
Author(s):  
M. Vizek ◽  
C. K. Pickett ◽  
J. V. Weil
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Interindividual Variation ◽  
Potential Contribution ◽  
Hypoxic Ventilatory Response ◽  
Peripheral Chemoreceptor ◽  
Interindividual Differences ◽  
Carotid Bodies ◽  
Considerable Interindividual Variation ◽  
Ventilatory Response To Hypoxia

There is considerable interindividual variation in ventilatory response to hypoxia in humans but the mechanism remains unknown. To examine the potential contribution of variable peripheral chemorecptor function to variation in hypoxic ventilatory response (HVR), we compared the peripheral chemoreceptor and ventilatory response to hypoxia in 51 anesthetized cats. We found large interindividual differences in HVR spanning a sevenfold range. In 23 cats studied on two separate days, ventilatory measurements were correlated (r = 0.54, P less than 0.01), suggesting stable interindividual differences. Measurements during wakefulness and in anesthesia in nine cats showed that although anesthesia lowered the absolute HVR it had no influence on the range or the rank of the magnitude of the response of individuals in the group. We observed a positive correlation between ventilatory and carotid sinus nerve (CSN) responses to hypoxia measured during anesthesia in 51 cats (r = 0.63, P less than 0.001). To assess the translation of peripheral chemoreceptor activity into expiratory minute ventilation (VE) we used an index relating the increase of VE to the increase of CSN activity for a given hypoxic stimulus (delta VE/delta CSN). Comparison of this index for cats with lowest (n = 5, HVR A = 7.0 +/- 0.8) and cats with highest (n = 5, HVR A = 53.2 +/- 4.9) ventilatory responses showed similar efficiency of central translation (0.72 +/- 0.06 and 0.70 +/- 0.08, respectively). These results indicate that interindividual variation in HVR is associated with comparable variation in hypoxic sensitivity of carotid bodies. Thus differences in peripheral chemoreceptor sensitivity may contribute to interindividual variability of HVR.

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