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J DeGoede

Publications and source records attributed to J DeGoede.

At least 37 records · Page 2Linked to original sources
PubMed1993

Maturation of the ventilatory response to CO2 in the newborn piglet.

In 12 piglets aged 0 to 1.5 d, we assessed the contribution of the peripheral and central chemoreceptors in mediating the ventilatory response to CO2 and the apneic threshold during normoxia (arterial O2 tension, 13 kPa) using the dynamic end-tidal forcing technique. With this technique, the ventilatory response is separated into a peripheral and a central component using a two-compartment model. Each component is described by a CO2 sensitivity, a time constant, a transport delay time, and an apneic threshold. The means of the estimated parameters per piglet were compared with those obtained in a previous study in piglets aged 2 to 11 d (Wolsink JG, Berkenbosch A, DeGoede J, Olievier CN: J Physiol (Lond) 456:39-48, 1992). The ratio of the peripheral CO2 sensitivity to the total CO2 sensitivity was found to be significantly lower in the younger group of piglets (0.14 +/- 0.10 versus 0.29 +/- 0.10), whereas the apneic threshold was significantly higher (2.52 +/- 1.12 kPa versus 1.06 +/- 1.46 kPa). We conclude that the peripheral chemoreceptors are responsive to CO2 shortly after birth. However, the ventilatory response to CO2 maturates in the first few days after birth by an increase in the relative contribution of the peripheral chemoreceptors to the total ventilatory response and a decreasing apneic threshold.

Aging↗
PubMed1992

The effects of hypoxia on the ventilatory response to sudden changes in CO2 in newborn piglets.

1. The ventilatory response to square-wave challenges in end-tidal partial pressure of CO2 (PCO2) was investigated at three levels of arterial PO2 (Pa,O2) in nineteen anaesthetized 2- to 11-day-old piglets. 2. The ventilatory responses, measured on a breath-to-breath basis, were separated into a peripheral and a central component using a two-compartment model. Both components were described by a CO2 sensitivity, a time constant, a time delay and a single offset. 3. Fifty-six responses were analysed against a background of normoxaemia (Pa,O2 = 12.70 +/- 0.72 kPa, mean +/- S.D.), fifty-three against a background of moderate hypoxaemia (Pa,O2 = 8.63 +/- 0.34 kPa) and fifty-one against a background of severe hypoxaemia (Pa,O2 = 4.98 +/- 0.30 kPa). 4. The sensitivity of the peripheral chemoreceptors in mediating the response to CO2 increased from 38.3 +/- 17.0 ml min-1 kPa-1 kg-1 during normoxaemia to 48.8 +/- 15.3 ml min-1 kPa-1 kg-1 during moderate hypoxaemia and to 72.9 +/- 24.0 ml min-1 kPa-1 kg-1 at severe hypoxaemia. 5. As compared with the central CO2 sensitivity during moderate hypoxaemia and normoxaemia (104.0 +/- 39.0 and 100.8 +/- 41.6 ml min-1 kPa-1 kg-1, respectively) it decreased to 85.9 +/- 54.1 ml min-1 kPa-1 kg-1 at severe hypoxaemia. 6. We conclude that in newborn piglets there is a positive interaction between hypoxia and hypercapnia at the level of the peripheral chemoreceptors while severe hypoxaemia reduced the CO2 sensitivity centrally.

Animals↗
PubMed1992

The ventilatory response to CO2 of the peripheral and central chemoreflex loop before and after sustained hypoxia in man.

1. The ventilatory response to sustained hypoxia is characterized by a fast increase due to the peripheral chemoreceptors followed by a slow decline. The mechanism of this decline is unknown. 2. To investigate the characteristics of the ventilatory response to sustained hypoxia ten healthy subjects were exposed to two consecutive periods of isocapnic hypoxia (arterial saturation 78%) separated by a 5 min exposure to isocapnic normoxia. 3. The acute hypoxic response to the second exposure to hypoxia (mean increase in ventilation +/- S.E.M., 7.2 +/- 0.8 l min-1) was significantly depressed (P = 0.04) compared to the first one (9.5 +/- 1.3 l min-1). 4. To investigate whether this depression was due to central or peripheral effects or both we measured, in the same ten subjects, the normoxic ventilatory response to CO2 before and after a period of 25 min of hypoxia using the technique of dynamic end-tidal forcing. 5. Each response was separated into a fast peripheral and slow central component characterized by a CO2 sensitivity, time constant, time delay and an off-set. 6. A total of thirty-six prehypoxic and thirty posthypoxic responses were analysed. The ventilatory CO2 sensitivities of the peripheral and central chemoreflex loops and the overall off-set (apnoeic threshold) after 25 min of hypoxia were somewhat larger than their prehypoxic values, but this effect was not significant. 7. We argue that the hypoxic ventilatory decline in man is due to a change in the off-set of the peripheral chemoreflex loop.

Adult↗
PubMed1991

Effect on ventilation of papaverine administered to the brain stem of the anaesthetized cat.

1. To investigate whether cerebral vasodilatation by itself contributes to the decrease in ventilation as found during brain stem hypoxia the role of cerebral vasodilatation on minute ventilation was investigated in twelve cats anaesthetized with alpha-chloralose-urethane. 2. Cerebral vasodilatation in the medulla oblongata was produced by adding papaverine to the blood perfusing the brain stem. 3. Papaverine at concentrations of 10-35 micrograms per millilitre of blood had an appreciable depressant effect on ventilation. At a concentration of 14.3 micrograms ml-1 the depression in ventilation averaged 0.7 +/- 0.1 l min-1. 4. The ventilatory response to stepwise changes in papaverine concentration could be adequately described with a single exponential function with a time delay. 5. The time constant of the ventilatory response following a step increase in papaverine concentration (134 +/- 15 s) was longer than that of the step decrease (105 +/- 10 s) in concentration (P = 0.034). The time delays of the ventilatory response (88 +/- 21 s and 53 +/- 8 s respectively) were not significantly different (P = 0.126). 6. The ventilatory response to stimulation of the peripheral chemoreceptors by hypoxia and of the central chemoreceptors by hypercapnia was not impaired by papaverine. 7. The results support the hypothesis that cerebral vasodilatation by itself contributes to the decrease in ventilation by brain stem hypoxia.

Animals↗
PubMed1991

Dynamic response of the peripheral chemoreflex loop to changes in end-tidal O2.

We studied the peripheral ventilatory response dynamics to changes in end-tidal O2 tension (PETO2) in 13 cats anesthetized with alpha-chloralose-urethan. The arterial O2 tension in the medulla oblongata was kept constant using the technique of artificial perfusion of the brain stem. At constant end-tidal CO2 tension, 72 ventilatory on-responses due to stepwise changes in PETO2 from hyperoxia (45-55 kPa) to hypoxia (4.7-9.0 kPa) and 62 ventilatory off-responses due to changes from hypoxia to hyperoxia were assessed. We fitted two exponential functions with the same time delay to the breath-by-breath ventilation and found a fast and a slow component in 85% of the ventilatory on-responses and in 76% of the off-responses. The time constant of the fast component of the ventilatory on-response was 1.6 +/- 1.5 (SD) s, and that of the off-response was 2.4 +/- 1.3 s; the gain of the on-response was smaller than that of the off-response (P = 0.020). For the slow component, the time constant of the on-response (72.6 +/- 36.4 s) was larger (P = 0.028) than that of the off-response (43.7 +/- 28.3 s), whereas the gain of the on-response exceeded that of the off-response (P = 0.031). We conclude that the ventilatory response of the peripheral chemoreflex loop to stepwise changes in PETO2 contains a fast and a slow component.

Animals↗
PubMed1991

Ventilatory sensitivities of peripheral and central chemoreceptors of young piglets to inhalation of CO2 in air.

In 20 piglets aged 2-12 d (mean 6.8 d) and anesthetized with alpha-chloralose-urethane, we investigated the contribution of the peripheral and central chemoreceptors to the ventilatory response to inhalation of CO2 in air. For this purpose we used the dynamic end-tidal forcing technique, applying square-wave changes in end-tidal CO2 tension of 1.5-2.0 kPa at a constant end-tidal O2 tension of 15 kPa. Each response, measured on a breath-to-breath basis, was separated into a fast peripheral and a slow central component by fitting the sum of two exponentials to the measured ventilation. Each component was characterized by a CO2 sensitivity, a time constant, a time delay, and an apneic threshold. The results showed that in 2- to 12-d-old piglets the peripheral chemoreceptors are responsive to CO2 during air breathing. The contribution of the peripheral chemoreceptors in mediating the response to CO2 averaged 30 +/- 10%. Within this age range we could not demonstrate a significant correlation of the parameters characterizing the dynamic ventilatory response to CO2 with postnatal age.

Age Factors↗
PubMed1990

On a pseudo-rebreathing technique to assess the ventilatory sensitivity to carbon dioxide in man.

1. The ventilatory sensitivity to carbon dioxide obtained from a step-ramp CO2 challenge was compared to the CO2 sensitivity from the steady-state method. 2. Experiments were performed in nine healthy male subjects against a background of hyperoxia and in two subjects against a background of normoxia. 3. In each subject experiments were performed in which the stepwise increase in end-tidal PCO2 above its resting value (A) was varied (range 0-2 kPa) and the subsequent rate of rise of end-tidal PCO2 in time (R) kept constant at 0.6 or 0.8 kPa min-1. 4. The results of the hyperoxic experiments show that the slope of the non-steady-state ventilatory response to CO2 (Sn) is greatly influenced by the magnitude of A. An increase of A of 1 kPa results in a 54% increase of the ratio non-steady-state ventilatory CO2 sensitivity to steady-state ventilatory CO2 sensitivity (Ss). The magnitude of R plays a minor role in determining Sn. The normoxic experiments gave similar results. 5. In experiments performed during hyperoxia Sn approximates Ss when the magnitude of A is 0.5 kPa. 6. The results are discussed and related to a physiological model. Simulations with representative values for the model parameters are in fair agreement with experimental values.

Carbon Dioxide↗
PubMed1990

The influence of oxygen on the ventilatory response to carbon dioxide in man.

1. The ventilatory response to isoxic square-wave challenges in end-tidal PCO2 was investigated at three levels of end-tidal PO2 (PET, O2) in nine healthy male subjects. 2. Twenty-seven responses against a background of mild hypoxia (PET, O2 approximately 10 kPa), sixty-seven against a background of normoxia (PET, O2 approximately 14.5 kPa) and seventy-six against a background of hyperoxia (PET, O2 approximately 70 kPa) were collected. 3. The breath-to-breath data were partitioned into a fast and a slow ventilatory component using a two-compartment model. 4. In the normoxic and hypoxic experiments the CO2 sensitivity of the fast component averaged to about 30 and 40% of the total CO2 sensitivity, respectively. In the hyperoxic experiments three subjects had no fast component in their response while in three others the CO2 sensitivity of the fast component averaged to about 24% of the total CO2 sensitivity. In the remaining three subjects the presence of a fast component was doubtful. 5. We argue that the fast component is due to the peripheral chemoreflex loop and the slow component to the central chemoreflex loop. 6. The central CO2 sensitivity and the apnoeic threshold (extrapolated end-tidal CO2 at zero ventilation in the steady state) were 15% smaller in hyperoxia than those in normoxia and hypoxia. In normoxia and mild hypoxia the central CO2 sensitivities were not significantly different. 7. We argue, that apart from peripheral oxygen-carbon dioxide interaction, there is evidence for central oxygen-carbon dioxide interaction in human subjects. 8. We conclude that in general there is a contribution to ventilation of the peripheral chemoreceptors during hyperoxia in man.

Adult↗
PubMed1990

Dynamics of the ventilatory response to central hypoxia in cats.

The dynamics of the effect of central hypoxia on ventilation were investigated by the technique of artificial perfusion of the brain stem in alpha-chloralose-urethan-anesthetized cats. A two-channel roller pump and a four-way valve allowed switching the gas exchanger into and out of the extracorporeal circuit which controlled the brain stem perfusion. When isocapnic hypoxia (arterial PO2 range 18-59 Torr) was limited to the brain stem, a decline in ventilation was consistently found. In 12 cats 47 steps into and 48 steps out of central hypoxia were made. The ventilatory response was fitted using least squares with a model that consisted of a latency followed by a single-exponential function. The latencies for the steps into and out of hypoxia were not significantly different (P = 0.14) and were 32.3 +/- 4.0 and 25.1 +/- 3.6 (SE) s, respectively. The time constant for the steps into hypoxia (149.7 +/- 8.5 s) was significantly longer (P = 0.0002) than for the steps out of hypoxia (105.5 +/- 10.1 s). The time constants for the increase and decrease in ventilation after step changes in the central arterial PCO2 found in a previous study (J. Appl. Physiol. 66: 2168-2172, 1989) were not significantly different (P greater than 0.2) from the corresponding time constants in this study (for 7 cats common to both studies). Theories of the mechanisms behind hypoxic ventilatory decline need to account for the long latency, the similarity between the time constants for the ventilatory response to O2 and CO2, and the differences between the time constants for increasing and decreasing ventilation.

Animals↗
PubMed1989

Almitrine and the peripheral ventilatory response to CO2 in hyperoxia and hypoxia.

The effects of almitrine bismesylate (initial intravenous dose 0.6 mg.kg-1 followed by continuous infusion of 0.4 mg.kg-1.h-1) on the ventilatory response to CO2 during hyperoxia and hypoxia were determined in 6 anaesthetized cats with the use of the dynamic end-tidal CO2 forcing technique. It was found that almitrine almost doubled the peripheral ventilatory sensitivity to CO2 during hyperoxia (mean PETO2 45.6 kPa) and also during mild hypoxia (mean PETO2 8.7 kPa). The apnoeic threshold (B) was in both cases shifted to substantially lower values than those of the control measurements. No significant effects of almitrine were found on the central ventilatory sensitivity to CO2 either during hyperoxia or during hypoxia. It is argued that the decrease of the apnoeic threshold may be due to an inhibitory effect of almitrine on the carotid body dopaminergic activity, and that the increase of the sensitivity to CO2 stems from a "hypoxia mimetic" mechanism.

Almitrine↗
PubMed1989

The ventilatory CO2 sensitivities from Read's rebreathing method and the steady-state method are not equal in man.

1. The ventilatory response to changes in end-tidal carbon dioxide tension during hyperoxia, obtained with Read's rebreathing method and a steady-state technique, were compared. 2. In ten young male subjects, forty successful rebreathing and thirteen steady-state experiments were performed on thirteen different morning sessions. 3. In all subjects the ventilatory CO2 sensitivities obtained with the rebreathing method (Sr) were appreciably larger than the steady-state CO2 sensitivities (Ss). The ratio Sr/Ss ranged from 1.40 to 2.59 with a mean value of 1.85. 4. We argue that these results can be explained by considering the effect of changes in cerebral blood flow upon increasing the arterial CO2 tension during rebreathing and the steady state. 5. We conclude that in general the CO2 sensitivity obtained with Read's rebreathing method does not represent the steady-state CO2 sensitivity.

Adult↗
PubMed1989

Dynamics of ventilatory response to step changes in PCO2 of blood perfusing the brain stem.

The technique of artificial brain stem perfusion was used to assess the ventilatory response to step changes in PCO2 of the blood perfusing the brain stem of the cat. A two-channel roller pump and a four-way valve allow switching the gas exchanger into and out of the extracorporeal circuit, which controlled the perfusion to the brain stem. Seven alpha-chloralose-urethan-anesthetized cats were studied, and 25 steps of increasing and 23 steps of decreasing PCO2 were analyzed. A model consisting of a single-exponential function with time delay best described the ventilatory response. The time delays 11.7 +/- 8.1 and 6.4 +/- 6.8 (SD) s (obtained from mean values per cat) for the step into and out of hypercapnia, respectively, were not significantly different (P = 0.10) and were of the order of the transit time of the tubing from valve to brain stem. The steady-state CO2 sensitivities obtained from the on- and off-responses were also not significantly different (P = 0.10). The time constants 87 +/- 25 and 150 +/- 51 s, respectively, were significantly different (P = 0.0002). We conclude that the central chemoreflex is adequately modeled by a single component with a different time constant for on- and off-responses.

Animals↗
PubMed1988

Effects of the dopamine antagonists haloperidol and domperidone on the normoxic ventilatory response to CO2 in cats.

We investigated the effects of the dopamine antagonists haloperidol and domperidone on the ventilatory response following square-wave changes in end-tidal CO2 during normoxia in chloralose-urethane anaesthetized cats. In 7 cats these responses were measured before (control, 28 runs) and after the administration of 1 mg/kg haloperidol i.v. (26 runs) and in 8 other cats before (39 runs) and after 0.5 mg/kg domperidone i.v. (34 runs). Each response was separated into a slow central and a fast peripheral part by fitting two exponential functions to the measured ventilation. These functions have as parameters a CO2 sensitivity, a time constant, a time delay and an apnoeic threshold B (extrapolated PETCO2 of the steady-state response curve at zero ventilation). Haloperidol significantly diminished the peripheral (Sp) and the central (Sc) ventilatory sensitivity to CO2 and the B-value (P less than 0.001). The ratio Sp/Sc, the time constants and the time delays were not significantly changed. Domperidone only diminished the B-value significantly (P less than 0.001). Since domperidone does not readily cross the blood-brain barrier, its effect was a CO2 independent increase of the ventilation mediated by the peripheral chemoreceptors. Haloperidol exhibited, besides the peripheral stimulatory effect a depressant central effect due to an action on the central integrative structures, resulting in a proportional decrease of Sp and Sc.

Animals↗
PubMed1988

Dynamic response of peripheral chemoreflex loop to changes in end-tidal CO2.

The dynamic ventilatory response of the peripheral chemoreflex loop after isoxic step changes in end-tidal PCO2 (PETCO2) (range 5-30 Torr) was studied in 12 alpha-chloralose-urethan-anesthetized cats. The technique of artificial brain stem perfusion allowed the response to be observed in isolation from the central chemoreflex loop. The data were fitted by an exponential with time delay. During normoxia the mean time constant and time delay (with SD) were 8.6 +/- 7.3 and 3.3 +/- 0.9 s, respectively (9 cats, 56 runs). During hypoxia [arterial PO2 (PaO2) approximately 60 Torr] these values were 6.0 +/- 4.5 and 2.9 +/- 0.9 s (6 cats, 38 runs). In 17 of the 94 runs an augmented breath occurred in the first three breaths after the stepwise increase in PETCO2. For these augmented breaths, tidal volume, inspiratory time, and expiratory time were not different from the next augmented breath occurring in the same run in the steady state. Neither a rate-sensitive component nor a central neural mechanism (central afterdischarge), with the property of maintaining an increased but slowly declining respiratory activity for some minutes after cessation of the PETCO2 challenge, was found. We conclude that the description of the ventilatory response of the peripheral chemoreflex loop to step changes in PETCO2 with a single exponential and time delay is adequate.

Animals↗
PubMed1987

Ventilatory responses to respiratory and metabolic acid-base disturbances in cats.

To determine the relative importance of the peripheral and central chemoreceptors in the ventilatory response to acute metabolic acid-base disturbances we measured the normoxic ventilatory response to acute respiratory and metabolic acidosis and alkalosis in 10 chloralose-urethane anesthetized cats using a technique of vertebral artery perfusion that allows one to independently manipulate the PaCO2, PaO2 and the H+ concentration of the blood in the systemic circulation (peripheral) and the blood perfusing the brain stem (central) (Berkenbosch et al., 1979). The ventilation could be satisfactorily described by a linear function of the peripheral and central arterial H+ concentration and the central PaCO2. Mean values (+/- SEM) found for the peripheral arterial H+ sensitivity and the isocapnic central arterial H+ sensitivity were 26.0 +/- 3.2 and 12.7 +/- 1.8 ml X min-1 X nM-1, respectively; the isohydric central arterial CO2 sensitivity was 545.9 +/- 96.7 ml X min-1 X kPa-1. We conclude that in the ventilatory response to an acute metabolic acid-base disturbance both the peripheral and central chemoreceptors play a role. However, the sensitivity of the peripheral chemoreceptors to isocapnic changes in the arterial H+ concentration is twice as large as the sensitivity of the central chemoreceptors. It is argued that in the adaptation of the ventilation to an acute metabolic acidosis the stimulatory effect of the peripheral chemoreceptors is counteracted by a diminished stimulation of the central chemoreceptors.

Acid-Base Imbalance↗
PubMed1986

G-protein-mediated interconversions of cell-surface cAMP receptors and their involvement in excitation and desensitization of guanylate cyclase in Dictyostelium discoideum.

In Dictyostelium discoideum cells, extracellular cAMP induces the rapid (within 2 s) activation of guanylate cyclase, which is followed by complete desensitization after about 10 s. cAMP binding to these cells is heterogeneous, showing a subclass of fast dissociating sites coupled to adenylate cyclase (A-sites) and a subclass of slowly dissociating sites coupled to guanylate cyclase (B-sites). The kinetics of the B-sites were further investigated on a seconds time scale. Statistical analysis of the association of [3H]cAMP to the B-sites and dissociation of the complex revealed that the receptor can exist in three states which interconvert according to the following scheme. (formula; see text). cAMP binds to the BF-state (off-rate 2.5 s) which rapidly (t1/2 = 3 s) converts to the BS-state (off-rate 15 s) and subsequently (without a detectable delay) into the BSS-state (off-rate 150 s). In membranes, both the BS- and BSS-states are converted to the BF-state by GTP and GDP, suggesting the involvement of a G-protein. Densensitized cells show a 80% reduction of the formation of the BSS-state, but no reduction of the BF- or BS-state. These data are combined into a model in which the transitions of the B-sites are mediated by a G-protein; activation of the G-protein and guanylate cyclase is associated with the transition of the BS- to the BSS-state of the receptor, whereas desensitization is associated with the inhibition of this transition.

Cell Membrane↗
PubMed1986

Effect of exogenous dopamine on the hypercapnic ventilatory response in cats during normoxia.

The effects of exogenous dopamine on the normoxic hypercapnic ventilatory response were assessed in nine chloralose-urethane anesthetized cats using the technique of dynamic end-tidal forcing. The ventilatory responses to step changes in end-tidal PCO2 (PETCO2) were measured before (control), during and after intravenous infusion of dopamine (420 micrograms X kg-1 X h-1). Each response was separated into a slow central and a fast peripheral chemoreflex loop by fitting two exponential functions to the measured ventilation. Both loops were described by a CO2 sensitivity, time constant, time delay and a single off-set B (extrapolated PETCO2 of the steady-state response curve at zero ventilation). Dopamine infusion only caused a significant increase of B (mean 0.3 kPa, P less than 0.0001) compared to control; the other model parameters were not significantly affected. After dopamine infusion B returned to significantly lower values (mean 0.2 kPa, P = 0.006) than in control. In two additional cats the dopamine administered to the blood which was artificially perfusing the brainstem, did not affect ventilation. We conclude that in normoxic cats the effect of exogenous dopamine on the ventilatory response to CO2 is due to a CO2 independent inhibition of the ventilatory drive which originates outside the brainstem.

Animals↗