Ventilatory behavior after hypoxia in C57BL/6J and A/J mice

2001 ◽  
Vol 91 (5) ◽  
pp. 1962-1970 ◽  
Author(s):  
Fang Han ◽  
Shyam Subramanian ◽  
Thomas E. Dick ◽  
Ismail A. Dreshaj ◽  
Kingman P. Strohl
Keyword(s):  
Airway Resistance ◽  
Minute Ventilation ◽  
Genetic Effect ◽  
Strain Differences ◽  
Whole Body ◽  
Environmental Forcing ◽  
Ventilatory Responses ◽  
Term Potentiation ◽  
Genetic Mechanisms ◽  
Whole Body Plethysmography

Given the environmental forcing by extremes in hypoxia-reoxygenation, there might be no genetic effect on posthypoxic short-term potentiation of ventilation. Minute ventilation (V˙e), respiratory frequency (f), tidal volume (Vt), and the airway resistance during chemical loading were assessed in unanesthetized unrestrained C57BL/6J (B6) and A/J mice using whole body plethysmography. Static pressure-volume curves were also performed. In 12 males for each strain, after 5 min of 8% O2 exposure, B6 mice had a prominent decrease inV˙e on reoxygenation with either air (−11%) or 100% O2 (−20%), due to the decline of f. In contrast, A/J animals had no ventilatory undershoot or f decline. After 5 min of 3% CO2-10% O2 exposure, B6 exhibited significant decrease in V˙e (−28.4 vs. −38.7%, air vs. 100% O2) and f (−13.8 vs. −22.3%, air vs. 100% O2) during reoxygenation with both air and 100% O2; however, A/J mice showed significant increase inV˙e (+116%) and f (+62.2%) during air reoxygenation and significant increase in V˙e (+68.2%) during 100% O2 reoxygenation. There were no strain differences in dynamic airway resistance during gas challenges or in steady-state total respiratory compliance measured postmortem. Strain differences in ventilatory responses to reoxygenation indicate that genetic mechanisms strongly influence posthypoxic ventilatory behavior.

Differential control of ventilation among inbred strains of mice

1994 ◽  
Vol 267 (5) ◽  
pp. R1371-R1377 ◽  
Author(s):  
C. G. Tankersley ◽  
R. S. Fitzgerald ◽  
S. R. Kleeberger
Keyword(s):  
Minute Ventilation ◽  
Inbred Strains ◽  
Whole Body ◽  
Genetic Determinants ◽  
Ventilatory Responses ◽  
Hypoxic Conditions ◽  
Inbred Strains Of Mice ◽  
Genetic Mechanisms ◽  
The Difference ◽  
Differential Control

The role genetic factors play in ventilatory control was examined by challenging eight inbred strains of mice to acute hypercapnia under normoxic and hypoxic conditions. Age-matched mice were exposed for 3-5 min to inspired gases of the following composition (FICO2:FIO2) 0.03:0.10, 2) 0.03:0.21, 3) 0.08:0.10, and 4) 0.08:0.21, with intermittent room air exposures. Breathing frequency (f) and tidal volume (VT) of unanesthetized, unrestrained mice were assessed by whole body plethysmography. During room air breathing, significant (P < 0.01) interstrain differences were noted in the pattern, but minute ventilation (VE) did not differ among the strains. Relative to room air, mild hypercapnia with hypoxia (0.03:0.10) significantly (P < 0.01) elevated VE in each strain, and the percent increase in VE of the DBA/2J strain was significantly (P < 0.05) greater than the other strains. The ventilatory response to these conditions was achieved primarily by a significant (P < 0.01) increase in f among the strains. During severely hypercapnic normoxia (0.08:0.21) and hypoxia (0.08:0.10), the increase in VE was significantly (P < 0.01) greatest in the C57BL/6J (B6) mice and least in the C3H/HeJ (C3) mice. The difference in hypercapnic VE between B6 and C3 strains was largely due to a significantly (P < 0.01) greater increase in VT by B6 mice. On the assumption that environmental factors were identical, these data suggest that genetic determinants govern interstrain variation in the magnitude and pattern of breathing during hypoxia and hypercapnia. Moreover, hypoxic and hypercapnic ventilatory responses appear to be influenced by different genetic mechanisms.

Acetazolamide protects against posthypoxic unstable breathing in the C57BL/6J mouse

2007 ◽  
Vol 103 (4) ◽  
pp. 1263-1268 ◽  
Author(s):  
Motoo Yamauchi ◽  
Jesse Dostal ◽  
Kingman P. Strohl
Keyword(s):  
Minute Ventilation ◽  
Periodic Breathing ◽  
Whole Body ◽  
Short Term ◽  
Term Potentiation ◽  
Coefficient Of Variability ◽  
Vehicle Treatment ◽  
Flow Through ◽  
Whole Body Plethysmography ◽  
Hypercapnic Response

Acetazolamide (Acz), a carbonic anhydrase inhibitor, is used to manage periodic breathing associated with altitude and with heart failure. We examined whether Acz would alter posthypoxic ventilatory behavior in the C57BL/6J (B6) mouse model of recurrent central apnea. Experiments were performed with unanesthetized, awake adult male B6 mice ( n = 9), ventilatory behavior was measured using flow-through whole body plethysmography. Mice were given an intraperitoneal injection of either vehicle or Acz (40 mg/kg), and 1 h later they were exposed to 1 min of 8% O2-balance N2 (poikilocapnic hypoxia) or 12% O2-3% CO2-balance N2 (isocapnic hypoxia) followed by rapid reoxygenation (100% O2). Hypercapnic response (8% CO2-balance O2) was examined in six mice. With Acz, ventilation, including respiratory frequency, tidal volume, and minute ventilation, in room air was significantly higher and hyperoxic hypercapnic ventilatory responsiveness was generally lower compared with vehicle. Poikilocapnic and isocapnic hypoxic ventilatory responsiveness were similar among treatments. One minute after reoxygenation, animals given Acz exhibited posthypoxic frequency decline, a lower coefficient of variability for frequency, and no tendency toward periodic breathing, compared with vehicle treatment. We conclude that Acz improves unstable breathing in the B6 model, without altering hypoxic response or producing short-term potentiation, but with some blunting of hypercapnic responsiveness.

scholarly journals Activation of Astrocytes in the Persistence of Post-hypoxic Respiratory Augmentation

2021 ◽  
Vol 12 ◽  
Author(s):  
Isato Fukushi ◽  
Kotaro Takeda ◽  
Mieczyslaw Pokorski ◽  
Yosuke Kono ◽  
Masashi Yoshizawa ◽  
...  
Keyword(s):  
Acute Hypoxia ◽  
Whole Body ◽  
High Dose ◽  
Ventilatory Responses ◽  
Adult Mice ◽  
Term Potentiation ◽  
Before And After ◽  
Whole Body Plethysmography ◽  
Hypoxic Gas Mixture

Acute hypoxia increases ventilation. After cessation of hypoxia loading, ventilation decreases but remains above the pre-exposure baseline level for a time. However, the mechanism of this post-hypoxic persistent respiratory augmentation (PHRA), which is a short-term potentiation of breathing, has not been elucidated. We aimed to test the hypothesis that astrocytes are involved in PHRA. To this end, we investigated hypoxic ventilatory responses by whole-body plethysmography in unanesthetized adult mice. The animals breathed room air, hypoxic gas mixture (7% O2, 93% N2) for 2min, and again room air for 10min before and after i.p. administration of low (100mg/kg) and high (300mg/kg) doses of arundic acid (AA), an astrocyte inhibitor. AA suppressed PHRA, with the high dose decreasing ventilation below the pre-hypoxic level. Further, we investigated the role of the astrocytic TRPA1 channel, a putative ventilatory hypoxia sensor, in PHRA using astrocyte-specific Trpa1 knockout (asTrpa1−/−) and floxed Trpa1 (Trpa1f/f) mice. In both Trpa1f/f and asTrpa1−/− mice, PHRA was noticeable, indicating that the astrocyte TRPA1 channel was not directly involved in PHRA. Taken together, these results indicate that astrocytes mediate the PHRA by mechanisms other than TRPA1 channels that are engaged in hypoxia sensing.

Effect of sleep on nocturnal bronchoconstriction and ventilatory patterns in asthmatics

1989 ◽  
Vol 67 (1) ◽  
pp. 243-249 ◽  
Author(s):  
R. D. Ballard ◽  
M. C. Saathoff ◽  
D. K. Patel ◽  
P. L. Kelly ◽  
R. J. Martin
Keyword(s):  
Airway Resistance ◽  
Minute Ventilation ◽  
The Other ◽  
Lower Airway ◽  
Sleep Laboratory ◽  
Sleep State ◽  
Asthmatic Patients ◽  
Ventilatory Responses ◽  
Rate Of Increase ◽  
Normal Controls

To assess the effect of sleep on airflow resistance and patterns of ventilation in asthmatic patients with nocturnal worsening, 10 adult subjects (6 asthmatic patients with nocturnal worsening, 4 normal controls) were monitored overnight in the sleep laboratory on two separate occasions. During 1 night, subjects were allowed to sleep normally, whereas during the other night all sleep was prevented. The six asthmatic patients demonstrated progressive increases in lower airway resistance (Rla) on both nights, but the rate of increase was twofold greater (P less than 0.0001) during the sleep night compared with the sleep prevention night. However, overnight decrements in forced expired volume in 1 s (FEV1) were similar over the 2 nights. The asthmatic patients maintained their minute ventilation as Rla increased during sleep, demonstrating a stable tidal volume with a mild increase in respiratory frequency. We conclude that in asthmatic patients with nocturnal worsening 1) Rla increases and FEV1 falls overnight regardless of sleep state, 2) sleep enhances the observed overnight increases in Rla, and 3) sleep does not abolish compensatory ventilatory responses to spontaneously occurring bronchoconstriction.

Maturation of baseline breathing and of hypercapnic and hypoxic ventilatory responses in newborn mice

2001 ◽  
Vol 281 (5) ◽  
pp. R1746-R1753 ◽  
Author(s):  
Sylvain Renolleau ◽  
Stéphane Dauger ◽  
Fanny Autret ◽  
Guy Vardon ◽  
Claude Gaultier ◽  
...  
Keyword(s):  
Cesarean Section ◽  
Tidal Volume ◽  
Mammalian Species ◽  
Whole Body ◽  
Body Plethysmography ◽  
Genetic Studies ◽  
Newborn Mice ◽  
Ventilatory Responses ◽  
Neuronal Mechanisms ◽  
Whole Body Plethysmography

Breathing during the first postnatal hours has not been examined in mice, the preferred mammalian species for genetic studies. We used whole body plethysmography to measure ventilation (V˙e), breath duration (TTOT), and tidal volume (Vt) in mice delivered vaginally (VD) or by cesarean section (CS). In experiment 1, 101 VD and 100 CS pups aged 1, 6, 12, 24, or 48 h were exposed to 8% CO2 or 10% O2for 90 s. In experiment 2, 31 VD pups aged 1, 12, or 24 h were exposed to 10% O2 for 5 min. Baseline breathing maturation was delayed in CS pups, but V˙eresponses to hypercapnia and hypoxia were not significantly different between VD and CS pups [at postnatal age of 1 h (H1): 48 ± 44 and 18 ± 32%, respectively, in VD and CS pups combined]. TheV˙e increase induced by hypoxia was greater at H12 (46 ± 27%) because of TTOT response maturation. At all ages, hypoxic decline was ascribable mainly to a Vtdecrease, and posthypoxic decline was ascribable to a TTOTincrease with apneas, suggesting different underlying neuronal mechanisms.

Stress-induced attenuation of the hypercapnic ventilatory response in awake rats

2001 ◽  
Vol 90 (5) ◽  
pp. 1729-1735 ◽  
Author(s):  
Richard Kinkead ◽  
Lydie Dupenloup ◽  
Nadine Valois ◽  
Roumiana Gulemetova
Keyword(s):  
Control System ◽  
Immobilization Stress ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Whole Body ◽  
Respiratory Homeostasis ◽  
Whole Body Plethysmography ◽  
Ventilatory Response To Hypoxia ◽  
Awake Rats

To test the hypothesis that stress alters the performance of the respiratory control system, we compared the acute (20 min) responses to moderate hypoxia and hypercapnia of rats previously subjected to immobilization stress (90 min/day) with responses of control animals. Ventilatory measurements were performed on awake rats using whole body plethysmography. Under baseline conditions, there were no differences in minute ventilation between stressed and unstressed groups. Rats previously exposed to immobilization stress had a 45% lower ventilatory response to hypercapnia (inspiratory CO2 fraction = 0.05) than controls. In contrast, stress exposure had no statistically significant effect on the ventilatory response to hypoxia (inspiratory O2 fraction = 0.12). Stress-induced attenuation of the hypercapnic response was associated with reduced tidal volume and inspiratory flow increases; the frequency and timing components of the response were not different between groups. We conclude that previous exposure to a stressful condition that does not constitute a direct challenge to respiratory homeostasis can elicit persistent (≥24 h) functional plasticity in the ventilatory control system.

The affinity of hemoglobin for oxygen affects ventilatory responses in mutant mice with Presbyterian hemoglobinopathy

2003 ◽  
Vol 285 (4) ◽  
pp. R747-R753 ◽  
Author(s):  
Masahiko Izumizaki ◽  
Masakatsu Tamaki ◽  
Yo-ichi Suzuki ◽  
Michiko Iwase ◽  
Takuji Shirasawa ◽  
...  
Keyword(s):  
Minute Ventilation ◽  
Globin Gene ◽  
Open Circuit ◽  
Mutant Mice ◽  
Whole Body ◽  
Wild Type ◽  
Peripheral Tissues ◽  
Ventilatory Responses ◽  
Significant Difference ◽  
In The Wild

The purpose of this study was to test whether chronically enhanced O2 delivery to tissues, without arterial hyperoxia, can change acute ventilatory responses to hypercapnia and hypoxia. The effects of decreased hemoglobin (Hb)-O2 affinity on ventilatory responses during hypercapnia (0, 5, 7, and 9% CO2 in O2) and hypoxia (10 and 15% O2 in N2) were assessed in mutant mice expressing Hb Presbyterian (mutation in the β-globin gene, β108 Asn → Lys). O2 consumption during normoxia, measured via open-circuit methods, was significantly higher in the mutant mice than in wild-type mice. Respiratory measurements were conducted with a whole body, unrestrained, single-chamber plethysmograph under conscious conditions. During hypercapnia, there was no difference between the slopes of the hypercapnic ventilatory responses, whereas minute ventilation at the same levels of arterial PCO2 was lower in the Presbyterian mice than in the wild-type mice. During both hypoxic exposures, ventilatory responses were blunted in the mutant mice compared with responses in the wild-type mice. The effects of brief hyperoxia exposure (100% O2) after 10% hypoxia on ventilation were examined in anesthetized, spontaneously breathing mice with a double-chamber plethysmograph. No significant difference was found in ventilatory responses to brief hypoxia between both groups of mice, indicating possible involvement of central mechanisms in blunted ventilatory responses to hypoxia in Presbyterian mice. We conclude that chronically enhanced O2 delivery to peripheral tissues can reduce ventilation during acute hypercapnic and hypoxic exposures.

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.

scholarly journals Ventilatory responses during and following hypercapnic gas challenge are impaired in male but not female endothelial NOS knock-out mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paulina M. Getsy ◽  
Sripriya Sundararajan ◽  
Walter J. May ◽  
Graham C. von Schill ◽  
Dylan K. McLaughlin ◽  
...  
Keyword(s):  
Tidal Volume ◽  
Minute Ventilation ◽  
Whole Body ◽  
Inspiratory Time ◽  
Male And Female ◽  
Knock Out ◽  
Ventilatory Responses ◽  
Knock Out Mice ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

AbstractThe roles of endothelial nitric oxide synthase (eNOS) in the ventilatory responses during and after a hypercapnic gas challenge (HCC, 5% CO2, 21% O2, 74% N2) were assessed in freely-moving female and male wild-type (WT) C57BL6 mice and eNOS knock-out (eNOS-/-) mice of C57BL6 background using whole body plethysmography. HCC elicited an array of ventilatory responses that were similar in male and female WT mice, such as increases in breathing frequency (with falls in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives. eNOS-/- male mice had smaller increases in minute ventilation, peak inspiratory flow and inspiratory drive, and smaller decreases in inspiratory time than WT males. Ventilatory responses in female eNOS-/- mice were similar to those in female WT mice. The ventilatory excitatory phase upon return to room-air was similar in both male and female WT mice. However, the post-HCC increases in frequency of breathing (with decreases in inspiratory times), and increases in tidal volume, minute ventilation, inspiratory drive (i.e., tidal volume/inspiratory time) and expiratory drive (i.e., tidal volume/expiratory time), and peak inspiratory and expiratory flows in male eNOS-/- mice were smaller than in male WT mice. In contrast, the post-HCC responses in female eNOS-/- mice were equal to those of the female WT mice. These findings provide the first evidence that the loss of eNOS affects the ventilatory responses during and after HCC in male C57BL6 mice, whereas female C57BL6 mice can compensate for the loss of eNOS, at least in respect to triggering ventilatory responses to HCC.

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