Ventilatory effects of acetazolamide in cats during hypoxemia

1992 ◽  
Vol 72 (5) ◽  
pp. 1717-1723 ◽  
Author(s):  
L. J. Teppema ◽  
F. Rochette ◽  
M. Demedts
Keyword(s):  
Steady State ◽  
Ventilatory Response ◽  
Significant Rise ◽  
Hypoxic Ventilatory Response ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Relative Contribution ◽  
Ventilatory Effects ◽  
Arterial Po2 ◽  
Mean Alveolar Pco2

In normoxemic cats, acetazolamide (ACTZ) has been shown to cause a large rise in ventilation (VE) but a decrease in peripheral chemoreceptor activity. The relative contribution of the peripheral chemoreceptors to ventilation is higher during hypoxemia than during normoxemia. Therefore, what are the effects of ACTZ during steady-state hypoxemia? The aims of this study in anesthetized cats were 1) to study the effect of ACTZ (50 mg/kg iv) on mean hypoxemic [arterial PO2 (PaO2) approximately 6 kPa] ventilation and 2) to study the effect of ACTZ on the isocapnic hypoxic ventilatory response. In the first study, in six cats with an inspiratory CO2 fraction of 0, ACTZ led to an insignificant rise in mean VE of 119 ml.min-1.kg-1 after 1 h. In five other cats maintained at an inspiratory CO2 fraction of 0.015, ACTZ resulted in a significantly larger response in VE (268 and 373 ml.min-1.kg-1 after 1 and 2 h, respectively). In the second study, before infusion in five cats, an isocapnic fall in mean PaO2 from 13 to 4.7 kPa led to a significant rise in mean VE of 385 ml.min-1.kg-1; 1 h later, the response (at the same mean alveolar PCO2) was reduced to an insignificant rise of 38 ml.min-1.kg-1. Before infusion four other cats showed a significant rise in mean VE of 390 ml.min-1.kg-1 when mean PaO2 was lowered isocapnically from 12.4 to 6.8 kPa; 2 h after infusion, an isocapnic fall in mean PaO2 from 13.9 to 7.2 kPa led to an insignificant rise of 112 ml.min-1.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventilatory effects of substance P, vasoactive intestinal peptide, and nitroprusside in humans

1990 ◽  
Vol 68 (1) ◽  
pp. 295-301 ◽  
Author(s):  
D. L. Maxwell ◽  
R. W. Fuller ◽  
C. M. Dixon ◽  
F. M. Cuss ◽  
P. J. Barnes
Keyword(s):  
Substance P ◽  
Vasoactive Intestinal Peptide ◽  
Carotid Body ◽  
Animal Studies ◽  
Ventilatory Response ◽  
Hypoxic Ventilatory Response ◽  
Peripheral Chemoreceptor ◽  
Hypotensive Action ◽  
Ventilatory Effects ◽  
Stimulation Of

Animal studies suggest that the neuropeptides, substance P and vasoactive intestinal peptide (VIP), may influence carotid body chemoreceptor activity and that substance P may take part in the carotid body response to hypoxia. The effects of these peptides on resting ventilation and on ventilatory responses to hypoxia and to hypercapnia have been investigated in six normal humans. Infusions of substance P (1 pmol.kg-1.min-1) and of VIP (6 pmol.kg-1.min-1) were compared with placebo and with nitroprusside (5 micrograms.kg-1.min-1) as a control for the hypotensive action of the peptides. Both peptides caused significantly less hypotension than nitroprusside. Substance P and nitroprusside caused significantly greater increases in ventilation and in the hypoxic ventilatory response than VIP. No changes were seen in hypercapnic sensitivity. The stimulation of ventilation and the differential effects on ventilatory chemosensitivity that accompanied hypotension are consistent either with stimulation of carotid body chemoreceptor activity or with an interaction with peripheral chemoreceptor input to the respiratory center, as is seen in animals. The similar cardiovascular but different ventilatory effects of the peptides suggest that substance P may also stimulate the carotid body in a manner independent of the effect of hypotension. This is consistent with a role of substance P in the hypoxic ventilatory response in humans.

Effect of temperature on central chemical control of ventilation in the alligator Alligator mississippiensis

1993 ◽  
Vol 179 (1) ◽  
pp. 261-272
Author(s):  
L. G. Branco ◽  
S. C. Wood
Keyword(s):  
Fourth Ventricle ◽  
Ventilatory Response ◽  
Pulmonary Ventilation ◽  
Gas Mixtures ◽  
Alligator Mississippiensis ◽  
Effect Of Temperature ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Ph Values ◽  
Arterial Ph

Central chemoreceptor function was assessed in unanesthetized alligators, Alligator mississippiensis, at body temperatures of 15, 25 and 35 degrees C. Two experiments were performed. In the first experiment, the fourth ventricle was perfused with mock cerebrospinal fluid (CSF) solutions of different pH values (7.1-7.9). Changes in pulmonary ventilation were evaluated with a pneumotachograph and arterial pH (pHa) was measured. Perfusion with low-pH solutions increased ventilation and arterial pH. Perfusion with high-pH solutions decreased ventilation and arterial pH. Mock CSF pH had a greater effect at higher temperatures. In the second experiment, the relative contributions of central and peripheral chemoreceptor drive to breathing were evaluated using hypercapnic gas mixtures to stimulate both central and peripheral chemoreceptors. Hypercapnia caused an increase in ventilation which was larger at higher temperatures. To stimulate only the peripheral chemoreceptors, the same hypercapnic gas mixtures were applied while the CSF pH of the fourth ventricle was kept constant by perfusion with a mock CSF solution. This reduced significantly the ventilatory response induced by hypercapnia. These data indicate that, regardless of the temperature, central chemoreceptors play a major role in the ventilatory regulation of the alligator. The change in pHa with temperature is compatible with the alphastat hypothesis.

Ventilatory response to moderate hypoxia in awake chemodenervated cats

1993 ◽  
Vol 74 (2) ◽  
pp. 805-810 ◽  
Author(s):  
W. Q. Long ◽  
G. G. Giesbrecht ◽  
N. R. Anthonisen
Keyword(s):  
Ventilatory Response ◽  
Systemic Blood Pressure ◽  
Initial Increase ◽  
Sham Operation ◽  
Biphasic Response ◽  
Peripheral Chemoreceptor ◽  
Moderate Hypoxia ◽  
Subsequent Decrease ◽  
End Tidal ◽  
Arterial Po2

In humans and cats the ventilatory response to 30 min of moderate hypoxia (arterial PO2 40–55 Torr) is biphasic: ventilation increases sharply for the first 5 min and then declines. In humans there is evidence that the decline is dependent on the initial increase. We therefore examined ventilatory responses to moderate isocapnic hypoxia in awake cats with and without carotid body denervation. Cats underwent denervation or a sham operation. Then they were studied in a Drorbaugh-Fenn plethysmograph while ventilation, arterial PO2, and end-tidal PO2 and PCO2 were measured. Three sham-operated and four denervated cats were studied with room air as the control. Sham animals demonstrated a biphasic response: ventilation rose to 211% of control at 5 min and fell to 114% of control at 25 min. Denervated animals showed neither the initial increase nor the subsequent decrease in ventilation. Three sham-operated and three denervated cats were studied with 2% CO2 added to the inspirate. Results were similar: intact cats showed a biphasic response to hypoxia, whereas denervated cats showed neither an increase nor a decrease in ventilation. Preliminary experiments showed that hypoxia was not associated with changes in CO2 output or systemic blood pressure in either denervated or intact animals. We conclude that depression of ventilation does not occur in awake denervated cats in response to moderate hypoxia and that the decline in ventilation that occurs in intact cats is in some way dependent on peripheral chemoreceptor output.

Ventilatory effects and interactions with change in PaO2 in awake goats

1991 ◽  
Vol 71 (4) ◽  
pp. 1254-1260 ◽  
Author(s):  
L. Daristotle ◽  
M. J. Engwall ◽  
W. Z. Niu ◽  
G. E. Bisgard
Keyword(s):  
Tidal Volume ◽  
Carotid Body ◽  
Ventilatory Response ◽  
Respiratory Frequency ◽  
Systemic Hypoxia ◽  
Ventilatory Effects ◽  
Arterial Po2

We utilized selective carotid body (CB) perfusion while changing inspired O2 fraction in arterial isocapnia to characterize the non-CB chemoreceptor ventilatory response to changes in arterial PO2 (PaO2) in awake goats and to define the effect of varying levels of CB PO2 on this response. Systemic hyperoxia (PaO2 greater than 400 Torr) significantly increased inspired ventilation (VI) and tidal volume (VT) in goats during CB normoxia, and systemic hypoxia (PaO2 = 29 Torr) significantly increased VI and respiratory frequency in these goats. CB hypoxia (CB PO2 = 34 Torr) in systemic normoxia significantly increased VI, VT, and VT/TI; the ventilatory effects of CB hypoxia were not significantly altered by varying systemic PaO2. We conclude that ventilation is stimulated by systemic hypoxia and hyperoxia in CB normoxia and that this ventilatory response to changes in systemic O2 affects the CB O2 response in an additive manner.

Effects of CO2 on immediate ventilatory response to O2 in preterm infants

1976 ◽  
Vol 41 (5) ◽  
pp. 609-611 ◽  
Author(s):  
S. Albersheim ◽  
R. Boychuk ◽  
M. M. Seshia ◽  
D. Cates ◽  
H. Rigatto
Keyword(s):  
Preterm Infants ◽  
Ventilatory Response ◽  
Background Concentrations ◽  
Peripheral Chemoreceptor ◽  
Co2 Response ◽  
Peripheral Chemoreceptors ◽  
Paradoxical Response

We wanted to know wheter the paradoxical response to CO2 under various background concentrations of O2 in preterm infants was mediated at the peripheral chemoreceptors. In five preterm infants we estimated peripheral chemoreceptor activity using the immediate change in ventilation (first 30 s) when 15%, 40%, 60%, or 100% O2 was substituted for 21% O2. Potentiation between O2 and CO2 was assessed by comparing the response with and without 4% CO2. CO2 enhanced the immediate hyperventilation with hypoxia (P less than 0.005) and reduced the immediate hypoventilation with hyperoxia (P less than 0.025 for 40% O2). This effect of CO2 increased from .00% to 15% O2 (P lessthan 0.05). These findings suggest: 1) CO2 interacts with O2 at the peripheral chemoreceptor level, and 2) because this interaction is more pronouncedwith hypoxia, the flatter CO2 response we observed with hypoxia was probably not mediated through the peripheral chemoreceptors and is likely to be central in origin.

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.

Ventilatory response in the fetal lamb following peripheral chemodenervation

1977 ◽  
Vol 42 (4) ◽  
pp. 630-635 ◽  
Author(s):  
D. E. Woodrum ◽  
T. A. Standaert ◽  
C. R. Parks ◽  
D. Belenky ◽  
J. Murphy ◽  
...  
Keyword(s):  
Ventilatory Response ◽  
Blood Gases ◽  
System Control ◽  
Fetal Blood ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Marked Variability ◽  
Fetal Lamb ◽  
Before And After ◽  
Chemical Stimuli

Carotid infusions of sodium cyanide solution and perfusions of hypoxemic or hypercapnic fetal blood were done before and after peripheral chemoreceptor denervation. Step changes in PaO2 ranged from -11 to -22 Torr; step changes in PaCO2 ranged from +17 to +42 Torr. The cyanide dose was 0.2 mg/kg per loop system. Control perfusions consisted of 25 ml of fetal blood without changes in pH and blood gases. A ventilatory response occurred in the majority of all experimental perfusions regardless of innervation status of the peripheral chemoreceptors. No response occurred with control perfusions. There was a marked variability in the time of onset of ventilatory activity with a delay of greater than 10 s occurring following most perfusions. These studies demonstrate that the fetus has an attenuated ventilatory response to chemical stimuli and that hypoxia stimulates ventilation in the absence of peripheral chemoreceptors.

Peripheral chemoreceptor function after carbonic anhydrase inhibition during moderate-intensity exercise

1999 ◽  
Vol 86 (5) ◽  
pp. 1544-1551 ◽  
Author(s):  
Barry W. Scheuermann ◽  
John M. Kowalchuk ◽  
Donald H. Paterson ◽  
David A. Cunningham
Keyword(s):  
Steady State ◽  
Carbonic Anhydrase ◽  
Ventilatory Threshold ◽  
Ventilatory Response ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Peripheral Chemoreceptor ◽  
Ventilatory Drive ◽  
Carbonic Anhydrase Inhibition ◽  
End Tidal

The effect of carbonic anhydrase inhibition with acetazolamide (Acz, 10 mg/kg) on the ventilatory response to an abrupt switch into hyperoxia (end-tidal [Formula: see text]= 450 Torr) and hypoxia (end-tidal[Formula: see text] = 50 Torr) was examined in five male subjects [30 ± 3 (SE) yr]. Subjects exercised at a work rate chosen to elicit an O2 uptake equivalent to 80% of the ventilatory threshold. Ventilation (V˙e) was measured breath by breath. Arterial oxyhemoglobin saturation (%[Formula: see text]) was determined by ear oximetry. After the switch into hyperoxia, V˙eremained unchanged from the steady-state exercise prehyperoxic value (60.6 ± 6.5 l/min) during Acz. During control studies (Con),V˙e decreased from the prehyperoxic value (52.4 ± 5.5 l/min) by ∼20% (V˙enadir = 42.4 ± 6.3 l/min) within 20 s after the switch into hyperoxia. V˙e increased during Acz and Con after the switch into hypoxia; the hypoxic ventilatory response was significantly lower after Acz compared with Con [Acz, change (Δ) inV˙e/[Formula: see text]= 1.54 ± 0.10 l ⋅ min−1 ⋅ [Formula: see text] −1; Con, ΔV˙e/[Formula: see text]= 2.22 ± 0.28 l ⋅ min−1 ⋅ [Formula: see text] −1]. The peripheral chemoreceptor contribution to the ventilatory drive after acute Acz-induced carbonic anhydrase inhibition is not apparent in the steady state of moderate-intensity exercise. However, Acz administration did not completely attenuate the peripheral chemoreceptor response to hypoxia.

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.

Vagal and chemoreceptor influences on abdominal muscle activity in awake lambs during hypoxia

1993 ◽  
Vol 74 (4) ◽  
pp. 1689-1696 ◽  
Author(s):  
J. P. Praud ◽  
E. Canet ◽  
I. Kianicka ◽  
C. Gaultier ◽  
M. Bureau
Keyword(s):  
Dynamic Control ◽  
Abdominal Muscle ◽  
Vagal Afferents ◽  
Emg Activity ◽  
Control Mechanisms ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Air Breathing ◽  
Relative Contribution ◽  
Afferent Information

The ventilatory response to hypoxia is a complex phenomenon involving several control mechanisms. We designed this study to examine the dynamic control of abdominal muscle expiratory electromyogram (EMG) activity during room-air breathing and hypoxia and then to analyze the relative contribution of the chemoreceptors and vagal afferents. We studied 12 11- to 22-day-old awake nonsedated lambs, six intact and six vagotomized. To assess the dynamic influence of peripheral chemoreceptors on abdominal muscle expiratory activity, we performed transient testing of peripheral chemoreceptor function (pure O2 and N2 inhalation, KCN injection). To assess the influence of central chemoreceptor afferents, we compared results obtained during hypocapnic and isocapnic 15-min hypoxic runs (fractional concentration of inspired O2 0.08) in each lamb. We also compared results obtained in intact and vagotomized lambs so that the importance of vagal afferents could be assessed. We consistently observed abdominal muscle expiratory EMG activity in each lamb, whether intact or vagotomized, during baseline room air breathing; further recruitment was observed during hypoxia. We also consistently observed abdominal muscle expiratory recruitment during hypocapnic hypoxia in each lamb, although it was significantly less marked than during isocapnic hypoxia. Our transient testing of peripheral chemoreceptor function showed, furthermore, that peripheral chemoreceptor afferents dynamically modulate abdominal muscle expiratory activity. Thus, during hypoxia in 11- to 22-day-old awake nonsedated lambs, increased afferent information from peripheral chemoreceptors forcefully enhances abdominal muscle expiratory activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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