Effect of a synthetic progestin on ventilatory response to hypoxia in anesthetized rats

1989 ◽  
Vol 67 (5) ◽  
pp. 1754-1758 ◽  
Author(s):  
H. Kimura ◽  
M. Mikami ◽  
T. Kuriyama ◽  
Y. Fukuda
Keyword(s):  
Regulatory Mechanism ◽  
Carotid Sinus ◽  
Ventilatory Response ◽  
Break Point ◽  
Male Rat ◽  
Carotid Sinus Nerve ◽  
Ventilatory Responses ◽  
Chlormadinone Acetate ◽  
Ventilatory Depression ◽  
Ventilatory Response To Hypoxia

Effects on ventilatory responses to progressive isocapnic hypoxia of a synthetic potent progestin, chlormadinone acetate (CMA), were determined in the halothane-anesthetized male rat. Ventilation during the breathing of hyperoxic gas was largely unaffected by treatment with CMA when carotid chemoreceptor afferents were kept intact. The sensitivity to hypoxia evaluated by hyperbolic regression analysis of the response curve did not differ between the control and CMA groups. The reduction of ventilation after bilateral section of the carotid sinus nerve (CSN) in hyperoxia was less severe in CMA-treated than in untreated animals. Furthermore, the CMA-treated rats showed a larger increase in ventilation during the hypoxia test and a lower PO2 break point for ventilatory depression. Inhibition of hypoxic ventilatory depression by CMA persisted even after the denervation of CSN. We conclude that exogenous progestin likely protects regulatory mechanism(s) for respiration against hypoxic depression through a stimulating action independent of carotid chemoreceptor afferents and without a change in the sensitivity of the ventilatory response to hypoxia.

scholarly journals Carotid sinus nerve transection abolishes the facilitation of breathing that occurs upon cessation of a hypercapnic gas challenge in male mice

2021 ◽  
Author(s):  
Paulina M. Getsy ◽  
Sripriya Sundararajan ◽  
Stephen John Lewis
Keyword(s):  
Carotid Sinus ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Nerve Transection ◽  
Carotid Sinus Nerve ◽  
Ventilatory Responses ◽  
Bilateral Carotid ◽  
Baseline Values ◽  
Freely Moving

Arterial pCO2 elevations increase minute ventilation via activation of chemosensors within the carotid body (CB) and brainstem. Although the roles of CB chemoafferents in the hypercapnic (HC) ventilatory response have been investigated, there are no studies reporting the role of these chemoafferents in the ventilatory responses to a HC challenge or the responses that occur upon return to room-air, in freely-moving mice. This study found that a HC challenge (5%CO2, 21% O2, 74% N2 for 15 min) elicited an array of responses, including increases in frequency of breathing (accompanied by decreases in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives in sham-operated (SHAM) adult male C57BL6 mice, and that return to room-air elicited a brief excitatory phase followed by gradual recovery of all parameters toward baseline values over a 15 min period. The array of ventilatory responses to the HC challenge in mice with bilateral carotid sinus nerve transection (CSNX) performed 7 days previously, occurred more slowly but reached similar maxima as SHAM mice. A major finding was responses upon return to room-air were dramatically lower in CSNX mice than SHAM mice, and the parameters returned to baseline values within 1-2 min in CSNX mice, whereas it took much longer in SHAM mice. These findings are the first evidence that CB chemoafferents play a key role in initiating the ventilatory responses to HC challenge in C57BL6 mice and are essential for the expression of post-HC ventilatory responses.

Effect of elastic loading on ventilatory response to hypoxia in conscious man

1975 ◽  
Vol 39 (4) ◽  
pp. 548-551 ◽  
Author(s):  
A. S. Rebuck ◽  
M. Betts ◽  
N. A. Saunders
Keyword(s):  
Ventilatory Response ◽  
Variable Speed ◽  
Ventilatory Responses ◽  
Elastic Load ◽  
Resistive Loading ◽  
Elastic Loading ◽  
Progressive Hypoxia ◽  
End Tidal ◽  
Linear Regressions ◽  
Ventilatory Response To Hypoxia

Ventilatory responses to isocapnic hypoxia, with and without an inspiratory elastic load (12.1 cmH2O/l), were measured in seven healthy subjects using a rebreathing technique. During each experiment, the end-tidal PCO2 was held constant using a variable-speed pump to draw gas from the rebreathing bag through a CO2 absorbing bypass. Studies with and without the load were performed in a formally randomized order for each subject. Linear regressions for rise in ventilation against fall in SaO2 were calculated. The range of unloaded responses was 0.74–1.38 1/min per 1% fall in SaO2 and loaded responses 0.71–1.56 1/min per 1% fall in SaO2. Elastic loading did not significantly alter the ventilatory response to progressive hypoxia (P greater than 0.2). In all subjects there was, however, a change in breathing pattern during loading, whereby increments in ventilation were attained by smaller tidal volumes and higher frequencies than in the control experiments. These results support the hypothesis previously proposed in our studies of resistive loading during progressive hypoxia, that a similar control pathway appears to be involved in response to the application of loads to breathing, whether ventilation is stimulated by hypoxia or hypercapnia.

Neonatal maternal separation enhances phrenic responses to hypoxia and carotid sinus nerve stimulation in the adult anesthetized rat

2005 ◽  
Vol 99 (1) ◽  
pp. 189-196 ◽  
Author(s):  
Richard Kinkead ◽  
Roumiana Gulemetova ◽  
Aida Bairam
Keyword(s):  
Nerve Stimulation ◽  
Maternal Separation ◽  
Carotid Sinus ◽  
Ventilatory Response ◽  
Male Rats ◽  
Hypoxic Ventilatory Response ◽  
Carotid Sinus Nerve ◽  
Neonatal Maternal Separation ◽  
Carotid Sinus Nerve Stimulation ◽  
Series Of Experiments

In awake animals, our laboratory recently showed that the hypoxic ventilatory response of adult male (but not female) rats previously subjected to neonatal maternal separation (NMS) is 25% greater than controls (Genest SE, Gulemetova R, Laforest S, Drolet G, and Kinkead R. J Physiol 554: 543–557, 2004). To begin mechanistic investigations of the effects of this neonatal stress on respiratory control development, we tested the hypothesis that, in male rats, NMS enhances central integration of carotid body chemoafferent signals. Experiments were performed on two groups of adult male rats. Pups subjected to NMS were placed in a temperature-controlled incubator 3 h/day from postnatal day 3 to postnatal day 12. Control pups were undisturbed. At adulthood (8–10 wk), rats were anesthetized (urethane; 1.6 g/kg), paralyzed, and ventilated with a hyperoxic gas mixture [inspired O2 fraction (FiO2) = 0.5], and phrenic nerve activity was recorded. The first series of experiments aimed to demonstrate that NMS-related enhancement of the inspiratory motor output (phrenic) response to hypoxia occurs in anesthetized animals also. In this series, rats were exposed to moderate, followed by severe, isocapnic hypoxia (FiO2 = 0.12 and 0.08, respectively, 5 min each). NMS enhanced both the frequency and amplitude components of the phrenic response to hypoxia relative to controls, thereby validating the use of this approach. In a second series of experiments, NMS increased the amplitude (but not the frequency) response to unilateral carotid sinus nerve stimulation (stimulation frequency range: 0.5–33 Hz). We conclude that enhancement of central integration of carotid body afferent signal contributes to the larger hypoxic ventilatory response observed in NMS rats.

scholarly journals Interindividual variability in the dose-specific effect of dopamine on carotid chemoreceptor sensitivity to hypoxia

2016 ◽  
Vol 120 (2) ◽  
pp. 138-147 ◽  
Author(s):  
Jacqueline K. Limberg ◽  
Blair D. Johnson ◽  
Walter W. Holbein ◽  
Sushant M. Ranadive ◽  
Michael T. Mozer ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ventilatory Response ◽  
Peripheral Resistance ◽  
Specific Effect ◽  
Cardiovascular Responses ◽  
Healthy Adults ◽  
Dopamine Infusion ◽  
Ventilatory Responses ◽  
Body Responsiveness ◽  
Ventilatory Response To Hypoxia

Human studies use varying levels of low-dose (1-4 μg·kg−1·min−1) dopamine to examine peripheral chemosensitivity, based on its known ability to blunt carotid body responsiveness to hypoxia. However, the effect of dopamine on the ventilatory responses to hypoxia is highly variable between individuals. Thus we sought to determine 1) the dose response relationship between dopamine and peripheral chemosensitivity as assessed by the ventilatory response to hypoxia in a cohort of healthy adults, and 2) potential confounding cardiovascular responses at variable low doses of dopamine. Young, healthy adults ( n = 30, age = 32 ± 1, 24 male/6 female) were given intravenous (iv) saline and a range of iv dopamine doses (1–4 μg·kg−1·min−1) prior to and throughout five hypoxic ventilatory response (HVR) tests. Subjects initially received iv saline, and after each HVR the dopamine infusion rate was increased by 1 μg·kg−1·min−1. Tidal volume, respiratory rate, heart rate, blood pressure, and oxygen saturation were continuously measured. Dopamine significantly reduced HVR at all doses ( P < 0.05). When subjects were divided into high ( n = 13) and low ( n = 17) baseline chemosensitivity, dopamine infusion (when assessed by dose) reduced HVR in the high group only ( P < 0.01), with no effect of dopamine on HVR in the low group ( P > 0.05). Dopamine infusion also resulted in a reduction in blood pressure (3 μg·kg−1·min−1) and total peripheral resistance (1–4 μg·kg−1·min−1), driven primarily by subjects with low baseline chemosensitivity. In conclusion, we did not find a single dose of dopamine that elicited a nadir HVR in all subjects. Additionally, potential confounding cardiovascular responses occur with dopamine infusion, which may limit its usage.

scholarly journals The Role of Carotid Sinus Nerve Input in the Hypoxic-Hypercapnic Ventilatory Response in Juvenile Rats

2020 ◽  
Vol 11 ◽  
Author(s):  
Paulina M. Getsy ◽  
Gregory A. Coffee ◽  
Stephen J. Lewis
Keyword(s):  
Carotid Sinus ◽  
Nucleus Tractus Solitarius ◽  
Minute Ventilation ◽  
Respiratory Pattern ◽  
Whole Body ◽  
Carotid Sinus Nerve ◽  
Sprague Dawley ◽  
Juvenile Rats ◽  
Ventilatory Responses ◽  
Chemosensory Pathway

In juvenile rats, the carotid body (CB) is the primary sensor of oxygen (O2) and a secondary sensor of carbon dioxide (CO2) in the blood. The CB communicates to the respiratory pattern generator via the carotid sinus nerve, which terminates within the commissural nucleus tractus solitarius (cNTS). While this is not the only peripheral chemosensory pathway in juvenile rodents, we hypothesize that it has a unique role in determining the interaction between O2 and CO2, and consequently, the response to hypoxic-hypercapnic gas challenges. The objectives of this study were to determine (1) the ventilatory responses to a poikilocapnic hypoxic (HX) gas challenge, a hypercapnic (HC) gas challenge or a hypoxic-hypercapnic (HH) gas challenge in juvenile rats; and (2) the roles of CSN chemoafferents in the interactions between HX and HC signaling in these rats. Studies were performed on conscious, freely moving juvenile (P25) male Sprague Dawley rats that underwent sham-surgery (SHAM) or bilateral transection of the carotid sinus nerves (CSNX) 4 days previously. Rats were placed in whole-body plethysmographs to record ventilatory parameters (frequency of breathing, tidal volume and minute ventilation). After acclimatization, they were exposed to HX (10% O2, 90% N2), HC (5% CO2, 21% O2, 74% N2) or HH (5% CO2, 10% O2, 85% N2) gas challenges for 5 min, followed by 15 min of room-air. The major findings were: (1) the HX, HC and HH challenges elicited robust ventilatory responses in SHAM rats; (2) ventilatory responses elicited by HX alone and HC alone were generally additive in SHAM rats; (3) the ventilatory responses to HX, HC and HH were markedly attenuated in CSNX rats compared to SHAM rats; and (4) ventilatory responses elicited by HX alone and HC alone were not additive in CSNX rats. Although the rats responded to HX after CSNX, CB chemoafferent input was necessary for the response to HH challenge. Thus, secondary peripheral chemoreceptors do not compensate for the loss of chemoreceptor input from the CB in juvenile rats.

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.

Ovalbumin sensitization alters the ventilatory responses to chemical challenges in guinea pigs

2005 ◽  
Vol 99 (5) ◽  
pp. 1782-1788 ◽  
Author(s):  
Fadi Xu ◽  
Jianguo Zhuang ◽  
Tongrong Zhou ◽  
Lu-Yuan Lee
Keyword(s):  
Guinea Pigs ◽  
Ventilatory Response ◽  
Underlying Mechanism ◽  
Right Atrial ◽  
Control Group ◽  
Ventilatory Responses ◽  
C Fibers ◽  
Arterial Blood ◽  
Aerosol Exposure ◽  
Ventilatory Response To Hypoxia

Patients with chronic bronchial asthma show a depressed ventilatory response to hypoxia (DVH), but the underlying mechanism remains unclear. We tested whether DVH existed in ovalbumin (Ova)-treated guinea pigs, an established animal model of asthma. Twelve guinea pigs were exposed to Ova (1% in saline) or saline aerosol (control) for 5 min, 5 days/wk, for 2 wk. After completing aerosol exposure, the animals were anesthetized and exposed to systemic hypoxia. Ova treatment had no effects on animal body weight, baseline cardiorespiratory variables, or arterial blood O2 and CO2 tensions, but it attenuated the ventilatory response to hypoxia (10 breaths of pure N2) by 65% ( P < 0.05). When the animals were subjected to intracarotid injections of sodium cyanide (20 μg) and doxapram (2 mg) to selectively stimulate carotid chemoreceptors, the ventilatory responses were reduced by 50% ( P < 0.05) and 74% ( P < 0.05), respectively. In contrast, Ova exposure failed to affect the ventilatory response to CO2 (7% CO2-21% O2-balance N2 for 5 min; P > 0.05). Furthermore, the apneic response evoked by stimulating bronchopulmonary C fibers (PCFs) with right atrial injection of capsaicin (5 μg) was markedly increased in the Ova-sensitized group (5.02 ± 1.56 s), compared with the control group (1.82 ± 0.45 s; P < 0.05). These results suggest that Ova sensitization induces a DVH in guinea pigs, which probably results from an attenuation of the carotid chemoreceptor-mediated ventilatory excitation and an enhancement of the PCF-mediated ventilatory inhibition.

Influences of Morphine on the Ventilatory Response to Isocapnic Hypoxia 

1997 ◽  
Vol 86 (6) ◽  
pp. 1342-1349 ◽  
Author(s):  
Aad Berkenbosch ◽  
Luc J. Teppema ◽  
Cees N. Olievier ◽  
Albert Dahan
Keyword(s):  
Carbon Dioxide ◽  
Steady State ◽  
Shape Parameter ◽  
Ventilatory Response ◽  
Depressant Effect ◽  
Ventilatory Responses ◽  
Before And After ◽  
End Tidal ◽  
Ventilatory Response To Hypoxia ◽  
Carbon Dioxide Sensitivity

Background The ventilatory response to hypoxia is composed of the stimulatory activity from peripheral chemoreceptors and a depressant effect from within the central nervous system. Morphine induces respiratory depression by affecting the peripheral and central carbon dioxide chemoreflex loops. There are only few reports on its effect on the hypoxic response. Thus the authors assessed the effect of morphine on the isocapnic ventilatory response to hypoxia in eight cats anesthetized with alpha-chloralose-urethan and on the ventilatory carbon dioxide sensitivities of the central and peripheral chemoreflex loops. Methods The steady-state ventilatory responses to six levels of end-tidal oxygen tension (PO2) ranging from 375 to 45 mmHg were measured at constant end-tidal carbon dioxide tension (P[ET]CO2, 41 mmHg) before and after intravenous administration of morphine hydrochloride (0.15 mg/kg). Each oxygen response was fitted to an exponential function characterized by the hypoxic sensitivity and a shape parameter. The hypercapnic ventilatory responses, determined before and after administration of morphine hydrochloride, were separated into a slow central and a fast peripheral component characterized by a carbon dioxide sensitivity and a single offset B (apneic threshold). Results At constant P(ET)CO2, morphine decreased ventilation during hyperoxia from 1,260 +/- 140 ml/min to 530 +/- 110 ml/ min (P &lt; 0.01). The hypoxic sensitivity and shape parameter did not differ from control. The ventilatory response to carbon dioxide was displaced to higher P(ET)CO2 levels, and the apneic threshold increased by 6 mmHg (P &lt; 0.01). The central and peripheral carbon dioxide sensitivities decreased by about 30% (P &lt; 0.01). Their ratio (peripheral carbon dioxide sensitivity:central carbon dioxide sensitivity) did not differ for the treatments (control = 0.165 +/- 0.105; morphine = 0.161 +/- 0.084). Conclusions Morphine depresses ventilation at hyperoxia but does not depress the steady-state increase in ventilation due to hypoxia. The authors speculate that morphine reduces the central depressant effect of hypoxia and the peripheral carbon dioxide sensitivity at hyperoxia.

Hypoxic ventilatory decline: site of action

1995 ◽  
Vol 79 (2) ◽  
pp. 373-374 ◽  
Author(s):  
P. A. Robbins
Keyword(s):  
Ventilatory Response ◽  
Good Evidence ◽  
Striking Similarity ◽  
Moderate Hypoxia ◽  
Ventilatory Responses ◽  
Site Of Action ◽  
Working Out ◽  
Sustained Hypoxia ◽  
Ventilatory Response To Hypoxia ◽  
Awake Animal

Although superficially similar, HVD appears to arise from different mechanisms in the awake animal as compared with the anesthetized animal. Consequently, the good evidence supporting a central site of action for hypoxia in the genesis of HVD in the anesthetized animal cannot be used as evidence for a central site of action for hypoxia in the awake animal. In their paper on HVD in the awake cat, Long et al. (10) conclude: “The striking similarity between feline and human ventilatory responses to moderate hypoxia illustrated by this and previous experiments leads us to believe that it is likely similar mechanisms apply to both species. Thus it seems probable that working out the mechanisms of the ventilatory response to hypoxia in the awake cat will go a long way toward solving the same problems in humans.” This activity should not neglect a consideration of whether adaptation at the carotid body during sustained hypoxia may be involved in the genesis of HVD in the awake state.

scholarly journals Essential role of hemoglobin beta-93-cysteine in posthypoxia facilitation of breathing in conscious mice

2014 ◽  
Vol 116 (10) ◽  
pp. 1290-1299 ◽  
Author(s):  
Benjamin Gaston ◽  
Walter J. May ◽  
Spencer Sullivan ◽  
Sean Yemen ◽  
Nadzeya V. Marozkina ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Essential Role ◽  
Carotid Sinus ◽  
Acute Hypoxia ◽  
Carotid Sinus Nerve ◽  
Short Term ◽  
Ventilatory Responses ◽  
Term Potentiation ◽  
Β Chain

When erythrocyte hemoglobin (Hb) is fully saturated with O2, nitric oxide (NO) covalently binds to the cysteine 93 residue of the Hb β-chain (B93-CYS), forming S-nitrosohemoglobin. Binding of NO is allosterically coupled to the O2 saturation of Hb. As saturation falls, the NO group on B93-CYS is transferred to thiols in the erythrocyte, and in the plasma, forming circulating S-nitrosothiols. Here, we studied whether the changes in ventilation during and following exposure to a hypoxic challenge were dependent on erythrocytic B93-CYS. Studies were performed in conscious mice in which native murine Hb was replaced with human Hb (hB93-CYS mice) and in mice in which murine Hb was replaced with human Hb containing an alanine rather than cysteine at position 93 on the Bchain (hB93-ALA). Both strains expressed human γ-chain Hb, likely allowing a residual element of S-nitrosothiol-dependent signaling. While resting parameters and initial hypoxic (10% O2, 90% N2) ventilatory responses were similar in hB93-CYS mice and hB93-ALA mice, the excitatory ventilatory responses (short-term potentiation) that occurred once the mice were returned to room air were markedly diminished in hB93-ALA mice. Further, short-term potentiation responses were virtually absent in mice with bilateral transection of the carotid sinus nerves. These data demonstrate that hB93-CYS plays an essential role in mediating carotid sinus nerve-dependent short-term potentiation, an important mechanism for recovery from acute hypoxia.

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