Effects of p-chlorophenylalanine on ventilatory control in goats

1983 ◽  
Vol 54 (1) ◽  
pp. 277-283 ◽  
Author(s):  
G. S. Mitchell ◽  
C. A. Smith ◽  
E. H. Vidruk ◽  
L. C. Jameson ◽  
J. A. Dempsey
Keyword(s):  
Tryptophan Hydroxylase ◽  
Ventilatory Response ◽  
Blood Gases ◽  
Co2 Production ◽  
Neural Pathways ◽  
Ventilatory Control ◽  
Arterial Pco2 ◽  
Carotid Bodies ◽  
Bilateral Carotid ◽  
O2 Concentration

The effects of tryptophan hydroxylase inhibition with p-chlorophenylalanine (PCPA; 100 mg/kg iv) on ventilatory control were studied in awake goats. Ventilation, CO2 production, and blood gases were measured 16–24 h after PCPA at rest and during mild exercise in normoxia and at rest in hypoxia and hypercapnia. PCPA increased ventilation 36% at rest, predominantly through an effect on respiratory frequency, and decreased arterial PCO2 (PaCO2) 6.5 Torr. Ventilatory gain in exercise (delta VI/deltaVCO2) was increased 20% by PCPA thereby maintaining PaCO2 at its new resting value. Hypoxia (fractional inspired O2 concentration = 0.12) had little effect on ventilation or PaCO2 at rest, either on control or on PCPA test days. Ventilatory sensitivity to CO2 at rest (delta VI/delta PaCO2) was unaffected by PCPA. Bilateral carotid body denervation (CBX) was performed in the animals, and experiments were repeated 3 mo after the first administration of PCPA. CBX alone decreased ventilation 29% and increased PaCO2 9.4 Torr. Administration of PCPA increased ventilation 35%, decreased PaCO2 by 10.2 Torr at rest, and increased ventilatory gain in exercise 26%. Thus carotid bodies are not necessary for the ventilatory response to PCPA. Furthermore, the primary neural pathways associated with exercise or hypercapnia are not specifically affected by inhibition of serotonin metabolism via PCPA.

Ventilatory effects of hypoxia and adenosine infusion in patients after bilateral carotid endarterectomy

1990 ◽  
Vol 78 (1) ◽  
pp. 25-31 ◽  
Author(s):  
T. L. Griffiths ◽  
S. J. Warren ◽  
A. D. B. Chant ◽  
S. T. Holgate
Keyword(s):  
Carotid Endarterectomy ◽  
Ventilatory Response ◽  
Adenosine Infusion ◽  
Respiratory Drive ◽  
Stimulant Effect ◽  
Carotid Bodies ◽  
Ventilatory Drive ◽  
Bilateral Carotid ◽  
Respiratory Stimulant ◽  
Ventilatory Effects

1. We have studied the carotid body contribution to hypoxic respiratory drive, using a hypoxic/hyperoxic switching technique, and the ventilatory response to intravenous infusion of adenosine, a recently described respiratory stimulant, in five patients with bilateral carotid endarterectomy. 2. The contribution made by the carotid bodies to total ventilatory drive during hypoxia varied from 2.5% to 45.9%. 3. The ventilatory response to adenosine infusion varied from a 7% decrease to a 25% increase in ventilation. 4. Those patients with intact hypoxic ventilatory drive showed respiratory stimulation, whereas of the two patients with attenuated chemoreflexes, one showed no stimulation and the other depression of ventilation in response to adenosine infusion. 5. We conclude that adenosine exerts its respiratory stimulant effect via an action on the peripheral chemoreceptors. This may coexist with a centrally mediated respiratory depression that is masked when the carotid bodies are intact.

Respiratory stimulation by female hormones in awake male rats

1991 ◽  
Vol 71 (1) ◽  
pp. 37-42 ◽  
Author(s):  
K. Tatsumi ◽  
M. Mikami ◽  
T. Kuriyama ◽  
Y. Fukuda
Keyword(s):  
Tidal Volume ◽  
Ventilatory Response ◽  
Blood Gases ◽  
Male Rats ◽  
Co2 Production ◽  
Male Rat ◽  
O2 Consumption ◽  
Estradiol Treatment ◽  
Respiratory Stimulation ◽  
Ventilatory Response To Co2

The respiratory effect of progestin differs among various animal species and humans. The rat does not hyperventilate in response to exogenous progestin. The present study was conducted to determine whether administration of combined progestin and estrogen prompts ventilatory stimulation in the male rat. Ventilation, blood gases, and metabolic rates (O2 consumption and CO2 production) were measured in the awake and unrestrained male Wistar rat. The combined administration of a synthetic potent progestin (TZP4238) and estradiol for 5 days significantly increased tidal volume and minute expiratory ventilation (VE), reduced arterial PCO2, and enhanced the ventilatory response to CO2 inhalation (delta VE/delta PCO2). On the other hand, respiratory frequency, O2 consumption, CO2 production, and body temperature were not affected. The arterial pH increased slightly, with a concomitant decrease in plasma [HCO3-]. Administration of either TZP4238 or estradiol alone or vehicle (Tween 80) had no effect on respiration, blood gases, and ventilatory response to CO2. The results indicated that respiratory stimulation following combined progestin plus estradiol treatment in the male rat involves activation of process(es) that regulate tidal volume and its augmentation during CO2 stimulus.

Interaction between CO2 production and ventilation in the hypoxic kitten

1993 ◽  
Vol 74 (2) ◽  
pp. 905-910 ◽  
Author(s):  
J. P. Mortola ◽  
T. Matsuoka
Keyword(s):  
Breathing Pattern ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Co2 Production ◽  
Depressant Effect ◽  
Arterial Pco2 ◽  
Ventilatory Responses ◽  
Parallel Increase ◽  
Shallow Breathing

We hypothesized that in the hypoxic newborn the drop in metabolic rate, and particularly in CO2 production (VCO2), contributes to the magnitude of the ventilatory response. Experiments were performed on unanesthetized newborn kittens in a warm [28–30 degrees C ambient temperature (Ta)] or cold (20 degrees C) environment. Breathing pattern and gaseous metabolism were measured by the barometric technique and the inflow-outflow O2 and CO2 difference, respectively. At 30 degrees C, hypoxia (10% O2) decreased VCO2 and induced rapid and shallow breathing, with little effect on minute ventilation (VE). Normoxic exposure to 20 degrees C determined a parallel increase in VE and metabolism; at this Ta, hypoxia decreased VCO2 more than at the higher Ta, and the drop in tidal volume (VT) was also proportionally larger; hence, at 20 degrees C, hypoxic VE was markedly below the normoxic values. Despite these changes in breathing pattern, at neither Ta during hypoxia did arterial PCO2 increase above the normoxic value; in fact, arterial PCO2 at 20 degrees C was slightly decreased because of the important drop in VCO2. Exposure to hypoxia with a CO2 load (inspired CO2 = 1, 3, or 5%) did not abolish the hypometabolic response; the hypoxic depressant effect on VT was either unchanged (by 1% CO2), completely offset (by 3% CO2), or reversed (by 5% CO2), with parallel effects on VE. The results are consistent with the hypothesis that in the newborn the level of CO2, by controlling VT, could represent a link between the metabolic and ventilatory responses to acute hypoxia.

DIDS decreases CSF HCO3- and increases breathing in response to CO2 in awake rabbits

1988 ◽  
Vol 64 (1) ◽  
pp. 397-403 ◽  
Author(s):  
E. E. Nattie ◽  
J. M. Adams
Keyword(s):  
Ventilatory Response ◽  
Ph Regulation ◽  
Minute Ventilation ◽  
Blood Gases ◽  
Disulfonic Acid ◽  
Carrier Protein ◽  
Related Effect ◽  
Arterial Pco2 ◽  
Ionic Mechanisms ◽  
Ventilatory Response To Co2

An inhibitor of the HCO3-/Cl- exchange carrier protein, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or vehicle was infused in mock cerebrospinal fluid (CSF) via the cisterna magna in conscious rabbits at 10 mumol/l for 40 min at 10 microliter/min. Neither treatment had any effect over 2-5 h on the non-CO2-stimulated CSF ion values or blood gases. With CO2 stimulation such that arterial PCO2 (PaCO2) was increased 25 Torr over 3 h, DIDS treatment significantly decreased the stoichiometrically opposite changes in CSF [HCO3-] and [Cl-] that normally accompany hypercapnia and reflect ionic mechanisms of CSF pH regulation. Expressed as delta CSF [HCO3-]/delta PaCO2, DIDS treatment decreased the CSF ionic response by 35%. In a separate paired study design DIDS administration via the same protocol had no effect on resting ventilation but significantly increased the ventilation and tidal volume responses to a 28-Torr increase in PaCO2. Expressed as change in minute ventilation divided by delta PaCO2, DIDS treatment produced a 39.6% increase. The results support the concept of a DIDS-inhibitable anion exchange carrier being involved in CSF pH regulation in hypercapnia and suggest a DIDS-related effect on the ventilatory response to CO2.

Effect of chronic resistive loading on hypoxic ventilatory responsiveness

1997 ◽  
Vol 82 (2) ◽  
pp. 500-507 ◽  
Author(s):  
Harly E. Greenberg ◽  
Rammohan S. Rao ◽  
Anthony L. Sica ◽  
Steven M. Scharf
Keyword(s):  
Ventilatory Response ◽  
Blood Gases ◽  
Endogenous Opioids ◽  
Ventilatory Control ◽  
Arterial Blood ◽  
Sham Surgery ◽  
Ventilatory Pattern ◽  
Resistive Loading ◽  
Ventilatory Response To Hypoxia

Greenberg, Harly E., Rammohan S. Rao, Anthony L. Sica, and Steven M. Scharf. Effect of chronic resistive loading on hypoxic ventilatory responsiveness. J. Appl. Physiol. 82(2): 500–507, 1997.—Depression of ventilation mediated by endogenous opioids has been observed acutely after resistive airway loading. We evaluated the effects of chronically increased airway resistance on hypoxic ventilatory responsiveness shortly after load imposition and 6 wk later. A circumferential tracheal band was placed in 200-g rats, tripling tracheal resistance. Sham surgery was performed in controls. Ventilation and the ventilatory response to hypoxia were measured by using barometric plethysmography at 2 days and 6 wk postsurgery in unanesthetized rats during exposure to room air and to 12% O2-5% CO2-balance N2. Trials were performed with and without naloxone (1 mg/kg ip). Room air arterial blood gases demonstrated hypercapnia with normoxia in obstructed rats at 2 days and 6 wk postsurgery. During hypoxia, a 30-Torr fall in[Formula: see text] occurred with no change in[Formula: see text]. Hypoxic ventilatory responsiveness was suppressed in obstructed rats at 2 days postloading. Naloxone partially reversed this suppression. However, hypoxic responsiveness at 6 wk was not different from control levels. Naloxone had a small effect on ventilatory pattern at this time with no overall effect on hypoxic responsiveness. This was in contrast to previously demonstrated long-term suppression of CO2 sensitivity in this model, which was partially reversible by naloxone only during the immediate period after load imposition. Endogenous opioids apparently modulate ventilatory control acutely after load imposition. Their effect wanes with time despite persistence of depressed CO2 sensitivity.

Metabolic-ventilatory interaction in conscious rats: effect of hypoxia and ambient temperature

1994 ◽  
Vol 76 (4) ◽  
pp. 1594-1599 ◽  
Author(s):  
C. Saiki ◽  
T. Matsuoka ◽  
J. P. Mortola
Keyword(s):  
Blood Pressure ◽  
Metabolic Rate ◽  
Ambient Temperature ◽  
Blood Gases ◽  
Male Rats ◽  
Co2 Production ◽  
O2 Consumption ◽  
Arterial Pco2 ◽  
Open Flow ◽  
Arterial Po2

Previous studies have indicated that the hypometabolic response to hypoxia depends on ambient temperature (Ta), being more pronounced in the cold. If metabolic rate were an important contributor to the level of ventilation (VE), the magnitude of the hyperpneic response to hypoxia should also depend on Ta. We tested this hypothesis on adult conscious male rats. In normoxia, a drop in Ta from 25 to 10 degrees C increased O2 consumption and CO2 production (VO2 and VCO2, respectively, measured by an open-flow technique) and VE (measured with the barometric method) by 80 and 60%, respectively, with no changes in blood gases. At both Ta, hypoxia (10% inspired O2, 33–35 Torr arterial PO2) induced the same degree of hyperventilation, i.e., the same drop in arterial PCO2 (about -13 Torr). The hyperventilation at 25 degrees C Ta was achieved exclusively by an increase in VE, whereas at 10 degrees C Ta the hyperpnea was minimal (+15%) and accompanied by a drop (-30%) in VO2 and VCO2. Diaphragmatic electromyograms confirmed the VE results. Changes in blood pressure were similar at both Ta. Addition of 3% CO2 to the inspired air further increased VE, indicating that the hypoxic rat was not breathing at its maximal VE at either Ta. We conclude that, in the rat, changes in metabolic rate play an important role in the VE response to hypoxia and that Ta influences the response because of its effect on the degree of hypoxic hypometabolism.

Arterial hypocapnia during exercise in beagle dogs

1986 ◽  
Vol 61 (2) ◽  
pp. 599-602 ◽  
Author(s):  
P. S. Clifford ◽  
J. T. Litzow ◽  
R. L. Coon
Keyword(s):  
Ventilatory Response ◽  
Blood Gases ◽  
Sampling Period ◽  
Work Load ◽  
Beagle Dogs ◽  
Tight Coupling ◽  
Arterial Pco2 ◽  
Arterial Blood ◽  
Response To Exercise ◽  
Arterial Po2

Previous investigators have assumed that during exercise there is a tight coupling of ventilation with CO2 delivery to the lungs such that arterial blood remains isocapnic. We measured arterial blood gases in a group of 10 beagle dogs in which arterial blood sampling could be accomplished via exteriorized carotid artery loops and in six of the same dogs following chronic pulmonary denervation. Samples were taken at rest, at 15-s intervals during the first minute of unrestrained treadmill exercise at 5.0 km/h, 0% grade, and then at 2 and 3 min at the same work load. Mean resting arterial PCO2 for the control dogs was 37.1 Torr. At the onset of exercise arterial PCO2 fell progressively to a nadir of 34.6 Torr during the 30- to 45-s sampling period. Samples at 2 and 3 min remained significantly hypocapnic (PCO2 = 34.8 Torr). The arterial PCO2 and pH responses to exercise in the lung-denervated dogs were not significantly different from those of the control dogs, although arterial PO2 was lower at rest and during exercise following denervation of the lungs. The arterial hypocapnia exhibited in intact beagle dogs at the onset of exercise persists into the steady state and suggests that there is not a tight coupling of ventilation with pulmonary CO2 delivery. The similarity of the response in lung-denervated dogs suggests that intrapulmonary receptors with afferents in the vagi are not the primary mediators of the ventilatory response to exercise.

Carotid chemoreceptors in ventilatory responses to changes in venous CO2 load

1981 ◽  
Vol 51 (6) ◽  
pp. 1398-1403 ◽  
Author(s):  
E. A. Phillipson ◽  
G. Bowes ◽  
E. R. Townsend ◽  
J. Duffin ◽  
J. D. Cooper
Keyword(s):  
Ventilatory Response ◽  
Venous Blood ◽  
Major Influence ◽  
Arterial Pco2 ◽  
Peripheral Venous Blood ◽  
Carotid Chemoreceptors ◽  
Ventilatory Responses ◽  
Carotid Bodies ◽  
Co2 Excretion

We examined the role of the carotid chemoreceptors in the ventilatory response to changes in venous CO2 load in 12 awake sheep using a venovenous extracorporeal perfusion circuit and two carbon dioxide membrane lungs (CDML). Three of the sheep had undergone surgical denervation of the carotid bodies (CBD). In the nine intact sheep, as CO2 was removed from or added to the peripheral venous blood through the CDML under normoxic conditions, there was a linear relationship between the rate of pulmonary CO2 excretion (VCO2) and the resulting rate of ventilation over a VCO2 range of 0--800% of control, so that arterial PCO2 remained close to isocapnic. In contrast, in the three CBD sheep, the ventilatory response to changes in VCO2 was significantly decreased under normoxic conditions, resulting in marked hypercapnia. The results indicate that the carotid chemoreceptors exert a major influence on the ventilatory response to changes in venous CO2 load.

Cardiorespiratory responses to hypoxia in intact and bilaterally vagotomized pigeons

1986 ◽  
Vol 61 (4) ◽  
pp. 1340-1345 ◽  
Author(s):  
G. M. Barnas ◽  
M. Gleeson ◽  
W. Rautenberg
Keyword(s):  
Partial Pressure ◽  
Respiratory Exchange Ratio ◽  
Cardiovascular Responses ◽  
Co2 Production ◽  
Co2 Partial Pressure ◽  
Carotid Bodies ◽  
O2 Partial Pressure ◽  
O2 Concentration ◽  
Cervical Vagotomy ◽  
Mixed Venous

Bilateral, cervical vagotomy in birds denervates, among other receptors, the carotid bodies. To test whether such neural section removes sensitivity to hypoxia, we measured respiratory, cardiovascular, and blood gas responses to hypoxia at 84-, 70-, and 49-Torr inspiratory O2 partial pressure (PIO2) in five pigeons with intact vagi and in five bilaterally, cervically vagotomized pigeons. Normoxic respiratory frequency (fresp) and expiratory flow rate (VE) were decreased after vagotomy. Intact pigeons showed large increases in VE in response to hypoxia, effected mostly by increases in fresp. VE also increased greatly in response to hypoxia in vagotomized pigeons, but increases were largely the result of tidal volume. O2 consumption, CO2 production, and respiratory exchange ratio increased slightly in all pigeons during hypoxia. Normoxic heart rate was greater after vagotomy; cardiac output increased in all pigeons in response to hypoxia, but stroke volume increased only in intact pigeons. During normoxia, arterial and mixed venous O2 partial pressure, O2 concentration, and pH were lower and arterial and mixed venous CO2 partial pressure was higher, after vagotomy. In all pigeons during hypoxia, arterial and mixed venous O2 and CO2 partial pressure and O2 concentration decreased and arterial and mixed venous pH increased; changes were roughly parallel in intact and vagotomized pigeons. The arteriovenous O2 concentration differences during normoxia and hypoxia were similar in all pigeons. We conclude that bilateral, cervical vagotomy in the pigeon causes hypoventilation and tachycardia during normoxia, but strong respiratory and cardiovascular responses to hypoxia are still present.

Changes in the VI-VCO2 relationship during exercise in goats: role of carotid bodies

1984 ◽  
Vol 57 (6) ◽  
pp. 1894-1900 ◽  
Author(s):  
G. S. Mitchell ◽  
C. A. Smith ◽  
J. A. Dempsey
Keyword(s):  
Principal Component ◽  
Blood Gases ◽  
Whole Body ◽  
Co2 Production ◽  
Similar Degree ◽  
Experimental Conditions ◽  
Serotonin Depletion ◽  
Arterial Blood ◽  
Carotid Bodies

To assess the role of carotid bodies in modulating the ventilation-CO2 production relationship, steady-state responses to mild exercise were determined in goats following several experimental manipulations that led to chronic changes in resting ventilation and arterial blood gases. The experimental conditions were 1) control, 2) whole body serotonin depletion (induced by p-chlorophenylalanine, 100 mg/kg), 3) carotid body denervation (CBX), and 4) serotonin depletion with CBX. Resting values of arterial CO2 pressure (Pco2) ranged from 32 to 48 Torr. In each condition, arterial Pco2 was regulated to a similar degree in exercise due to changes in the slope of the ventilation-CO2 production relationship (delta Vi/delta Vco2) in accordance with the requirements of gas exchange. delta Vi/delta Vco2 increased with serotonin depletion both before and after CBX. The principal component of ventilation contributing to changes in delta Vi/delta Vco2 was tidal volume. These results suggest a basic property of the ventilatory control system whereby enhanced ventilatory activity at rest is associated with an increased ventilatory response to exercise via a mechanism that does not require peripheral chemoreceptors.

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