Biomedical subjects

A Berkenbosch

Publications and source records attributed to A Berkenbosch.

At least 37 records · Page 2Linked to original sources

PubMed1995

Influences of subanesthetic isoflurane on ventilatory control in humans.

BACKGROUND: The purpose of this study was to quantify in humans the effects of subanesthetic isoflurane on the ventilatory control system, in particular on the peripheral chemoreflex loop. Therefore we studied the dynamic ventilatory response to carbon dioxide, the effect of isoflurane wash-in upon sustained hypoxic steady-state ventilation, and the ventilatory response at the onset of 20 min of isocapnic hypoxia. METHODS: Study 1: Square-wave changes in end-tidal carbon dioxide tension (7.5-11.5 mmHg) were performed in eight healthy volunteers at 0 and 0.1 minimum alveolar concentration (MAC) isoflurane. Each hypercapnic response was separated into a fast, peripheral component and a slow, central component, characterized by a time constant, carbon dioxide sensitivity, time delay, and off-set (apneic threshold). Study 2: The ventilatory changes due to the wash-in of 0.1 MAC isoflurane, 15 min after the induction of isocapnic hypoxia, were studied in 11 healthy volunteers. Study 3: The ventilatory responses to a step decrease in end-tidal oxygen (end-tidal oxygen tension from 110 to 44 mmHg within 3-4 breaths; duration of hypoxia 20 min) were assessed in eight healthy volunteers at 0, 0.1, and 0.2 MAC isoflurane. RESULTS: Values are reported as means +/- SF. Study 1: The peripheral carbon dioxide sensitivities averaged 0.50 +/- 0.08 (control) and 0.28 +/- 0.05 l.min-1.mmHg-1 (isoflurane; P < 0.01). The central carbon dioxide sensitivities (control 1.20 +/- 0.12 vs. isoflurane 1.04 +/- 0.11 l.min-1.mmHg-1) and off-sets (control 36.0 +/- 0.1 mmHg vs. isoflurane 34.5 +/- 0.2 mmHg) did not differ between treatments. Study 2: Within 30 s of exposure to 0.1 MAC isoflurane, ventilation decreased significantly, from 17.7 +/- 1.6 (hypoxia, awake) to 15.0 +/- 1.5 l.min-1 (hypoxia, isoflurane). Study 3: At the initiation of hypoxia ventilation increased by 7.7 +/- 1.4 (control), 4.1 +/- 0.8 (0.1 MAC; P < 0.05 vs. control), and 2.8 +/- 0.6 (0.2 MAC; P < 0.05 vs. control) l.min-1. The subsequent ventilatory decrease averaged 4.9 +/- 0.8 (control), 3.4 +/- 0.5 (0.1 MAC; difference not statistically significant), and 2.0 +/- 0.4 (0.2 MAC; P < 0.05 vs. control) l.min-1. There was a good correlation between the acute hypoxic response and the hypoxic ventilatory decrease (r = 0.9; P < 0.001). CONCLUSIONS: The results of all three studies indicate a selective and profound effect of subanesthetic isoflurane on the peripheral chemoreflex loop at the site of the peripheral chemoreceptors. We relate the reduction of the ventilatory decrease of sustained hypoxia to the decrease of the initial ventilatory response to hypoxia.

Adult↗

PubMed1995

Strength of the Breuer-Hering inflation reflex in term and preterm infants.

The effect of the presence of the respiratory distress syndrome (RDS) or related factors (static compliance of the respiratory system and transcutaneous blood gases) and gestational age on the strength of the Breuer-Hering inflation reflex (BHIR) was studied in three groups of infants. Twenty-six ventilated preterm infants with and without RDS were studied 6 h after birth (group 1). In 24 preterm infants, we followed the development of reflex strength during the first year of life (group 2). Twenty-one healthy nonintubated term infants were studied within the first week of life (group 3). The BHIR was initiated by end-inspiratory occlusions, and the strength was characterized by the ratio of expiratory time after and without preceding airway occlusion. The static compliance of the respiratory system in ventilated infants was assessed by the multiple-occlusion technique. In group 1, reflex strength declined with increasing gestational age; in the presence of RDS or low respiratory compliance, the decline was less. Transcutaneous blood gases did not affect reflex strength. At term age, reflex strength was similar in spontaneously breathing preterm (group 2) and term infants (group 3). The BHIR decreased in strength during the first year after preterm birth. We conclude that 1) the strength of the BHIR decreases with increasing gestational and postnatal ages and 2) RDS, due to changes in respiratory system mechanics, causes an increase in reflex strength.

Age Factors↗

PubMed1994

The influence of indomethacin on the ventilatory response to CO2 in newborn anaesthetized piglets.

1. Indomethacin, a cyclo-oxygenase inhibitor, decreases baseline values of cerebral blood flow, attenuates the cerebrovascular sensitivity to CO2 and stimulates ventilation in newborn piglets. 2. In twelve newborn anaesthetized piglets we investigated the influence of indomethacin on the ventilatory response to CO2 using the dynamic end-tidal forcing technique by applying square-wave changes in end-tidal CO2 tension of 1.5-2.0 kPa at constant end-tidal PO2 of 15 kPa. 3. Each response, measured on a breath-to-breath basis, is separated into a fast peripheral and a slow central component with each component characterized by a CO2 sensitivity, a time constant, a time delay and an apnoeic threshold. 4. The results showed that indomethacin increases the central CO2 sensitivity from 232 +/- 38 to 292 +/- 43 ml min-1 kPa-1 (mean +/- S.E.M.). Neither the peripheral CO2 sensitivity nor the apnoeic threshold changed. 5. The central on-transient and off-transient time constants increased from 50.0 +/- 7.4 and 81.0 +/- 9.6 s, respectively, to 69.1 +/- 9.8 and 139.9 +/- 13.4 s after indomethacin. 6. Using a physiological model we argue that the respiratory effects of indomethacin are due to effects on cerebral blood flow.

Anesthesia↗

PubMed1994

Hypercapnia induces c-fos expression in neurons of retrotrapezoid nucleus in cats.

To investigate which neurons in the medulla oblongata produced the nuclear protein FOS during stimulation of respiration by hypercapnia, we subjected six anaesthetized cats to 10% CO2 in air for one hour. Four animals inhaled room air. Coronal sections from the medulla oblongata were processed for FOS immunohistochemistry. Only the retrotrapezoid nucleus (RTN) of the animals exposed to CO2 contained a large population of labelled neurons. This indicates that RTN neurons are strongly activated during hypercapnia.

Animals↗

PubMed1994

Ventilatory interaction between hypoxia and hypercapnia in piglets shortly after birth.

In 12 piglets aged 0-1.5 days we assessed the relative contribution of the peripheral and central chemoreceptors in mediating the ventilatory response to CO2 at three levels of arterial O2 tension 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 time and a single apnoeic threshold. The results showed that the sensitivity of the peripheral chemoreceptors significantly (P < 0.01) increased from 25.0 +/- 23.6 ml.min-1.kPa-1.kg-1 (mean +/- SD) during normoxia (PaO2 = 12.8 +/- 0.3 kPa) to 42.5 +/- 29.4 ml.min-1.kPa-1.kg-1 during moderate hypoxia (PaO2 = 8.8 +/- 0.4 kPa) and to 80.2 +/- 44.4 ml.min-1.kPa-1.kg-1 at severe hypoxia (PaO2 = 5.1 +/- 0.3 kPa). There was no significant effect of the level of PaO2 on the other parameters. The results were compared with those obtained in a previous study in piglets aged 2-11 days. It showed that the interaction strength at the level of the peripheral chemoreceptors, defined as the negative ratio of the change in the peripheral CO2 sensitivity to the changes in PaO2 was greater in the younger piglets. From these results we conclude that in the newborn piglet the positive ventilatory interaction between hypoxia and hypercapnia at the level of the peripheral chemoreceptors is already developed shortly after birth and becomes smaller during development.

Animals↗

PubMed1994

Effects of subanesthetic halothane on the ventilatory responses to hypercapnia and acute hypoxia in healthy volunteers.

BACKGROUND: The peripheral chemoreceptors are responsible for the ventilatory response to hypoxia (acute hypoxic response) and for 30% of the normoxic hypercapnic ventilatory response. To quantify the effects of subanesthetic concentrations of halothane on the respiratory control system, in particular on the peripheral chemoreceptors, we studied the response of humans to carbon dioxide and oxygen at two subanesthetic concentrations of halothane. METHODS: Square-wave changes in end-tidal carbon dioxide tension (7.5-11.3 mmHg) and step decreases in end-tidal oxygen tension (arterial hemoglobin oxygen saturation 82 +/- 2%; duration of hypoxia 5 min) were performed in nine healthy male subjects during 0, 0.05 (HA-1), and 0.1 minimum alveolar concentration (HA-2) halothane. Each hypercapnic response was separated into a fast, peripheral component and a slow, central component, characterized by a time constant, carbon dioxide sensitivity, time delay, and off-set. RESULTS: Fifty-six carbon dioxide responses and 27 oxygen responses were obtained. The peripheral carbon dioxide sensitivities averaged to 0.76 +/- 0.14 l.min-1.mmHg-1 (control), 0.50 +/- 0.12 l.min-1.mmHg-1 (HA-1), and 0.30 +/- 0.08 l.min-1.mmHg-1 (HA-2; P < 0.01 vs. control). The central carbon dioxide sensitivity did not differ significantly among treatment groups (control, 1.47 +/- 0.22 l.min-1.mmHg-1; HA-1, 1.41 +/- 0.51 l.min-1.mmHg-1; and HA-2, 1.23 +/- 0.30 l.min-1.mmHg-1). The time constants of the central chemoreflex loop showed a large decrease during the administration of 0.1 minimum alveolar concentration halothane. The acute hypoxic response declined from 15.0 +/- 3.9 l.min-1 to 10.9 +/- 2.9 l.min-1 (HA-1) and 4.8 +/- 1.4 l.min-1 (HA-2; P < 0.01 vs. control and HA-1). All values are means +/- SEM. CONCLUSIONS: The results show depression of the ventilatory responses to hypoxia and hypercapnia during inhalation of subanesthetic concentrations of halothane. The depression is attributed to a selective effect of halothane on the peripheral chemoreflex loop. The oxygen and carbon dioxide responses mediated by the peripheral chemoreceptors are affected proportionally. It is argued that the decrease in central time constants is caused by an effect of halothane on central neuronal dynamics.

Administration, Inhalation↗

PubMed1994

Effects of morphine and physostigmine on the ventilatory response to carbon dioxide.

BACKGROUND: It has been reported that physostigmine antagonizes morphine-induced respiratory depression, but it is not known whether this is due to a central chemoreceptor effect, an effect on the peripheral chemoreflex loop, or both. We therefore assessed the effect of morphine and physostigmine on the normoxic hypercapnic ventilatory response mediated by the central and peripheral chemoreceptors in ten alpha-chloralose-urethan-anesthetized cats. METHODS: The breath-by-breath ventilatory responses to stepwise changes in end-tidal CO2 tension were determined before (control), after administration of morphine hydrochloride (0.15 mg.kg-1) and during intravenous infusion of physostigmine salicylate (bolus of 0.05 mg.kg-1 followed by 0.025 mg.kg-1.h-1). Each response was separated into a central and a peripheral chemoreflex characterized by CO2 sensitivity (Sc and Sp), time constant, time delay, and apneic threshold (a single off-set B). RESULTS: Morphine increased B and decreased Sc and Sp (P < 0.01), but not the ratio Sp/Sc. Subsequent infusion of physostigmine decreased B (P < 0.01), without further change of Sp and Sc. Premedication with physostigmine decreased B, Sp and Sc (P < 0.01) vs. control, but not Sp/Sc. Subsequent administration of morphine decreased Sp and Sc further but increased B (P < 0.01), while Sp/Sc remained constant. CONCLUSIONS: Because morphine diminishes the Sc and Sp of the chemoreflex loop to the same extent this depressant effect is presumably due to an action on the respiratory integrating centers rather than on the peripheral and central chemoreceptors as such and is not antagonized by physostigmine. We argue that the increase in B may be due to changes in the amount of acetylcholine available in the brain and can be antagonized by physostigmine.

Anesthesia↗

PubMed1994

Influence of a subanesthetic concentration of halothane on the ventilatory response to step changes into and out of sustained isocapnic hypoxia in healthy volunteers.

BACKGROUND: In humans the ventilatory response to isocapnic hypoxia is biphasic: an initial increase in minute ventilation (VE) from baseline, the acute hypoxic response, is followed after 3-5 min by a slow ventilatory decay, the hypoxic ventilatory decline, and a new steady state, 25-40% greater than baseline VE, is reached in about 15-20 min. The transition from 20 min of isocapnic hypoxia into normoxia results in a rapid decrease in VE, the off-response. In humans, halothane, at subanesthetic concentrations, is known to decrease the acute hypoxic response. In order to investigate the effects of halothane on sustained hypoxia we quantified the effects of 0.15 minimum alveolar concentration halothane on the ventilatory response at the onset of 20 min of hypoxia and at the termination of 20 min of hypoxia by normoxia in healthy volunteers. METHODS: Step changes in end-tidal oxygen tension were performed against a background of constant mild hypercapnia (end-tidal carbon dioxide tension about 1 mmHg above individual resting values) in fourteen male subjects. The end-tidal oxygen tension was forced as follows: 5-10 min at 110 mmHg, 20 min at 44 mmHg, and 10 min at 110 mmHg. In each subject we performed one trial before and one during 0.15 minimum alveolar concentration halothane administration. RESULTS: Ten responses into hypoxia and nine out of hypoxia were considered for analysis. All control trials were performed during wakefulness. Using behavioral characteristics, the central nervous system arousal state of the subjects during halothane inhalation was defined as "anesthesia-induced hypnosis." The acute hypoxic response averaged 10.4 +/- 4.7 l/min for control versus 3.7 +/- 2.4 l/min for halothane trials (P < 0.01). The hypoxic ventilatory decline was 4.8 +/- 2.5 l/min versus 3.9 +/- 2.9 l/min (NS), the off-response was 6.7 +/- 3.2 l/min versus 3.7 +/- 3.0 l/min (P < 0.05) for control versus halothane, respectively. All values are mean +/- SD. CONCLUSIONS: Our results indicate that halothane caused VE to be less than control levels during acute and sustained hypoxia as well as when sustained hypoxia is replaced by normoxia. It is argued that the depression of VE during acute hypoxia is attributed to an effect of halothane on the peripheral chemoreceptors. During sustained hypoxia halothane had no effect on the magnitude of the hypoxic ventilatory decrease, which is probably related to an increase by halothane of inhibitory neuromodulators within the central nervous system. With halothane, the ventilatory decrease when sustained hypoxia is replaced by normoxia is related to the removal of the hypoxic drive at the site of the peripheral chemoreceptors.

Adult↗

PubMed1994

Does subanesthetic isoflurane affect the ventilatory response to acute isocapnic hypoxia in healthy volunteers?

BACKGROUND: Differences in results studying the effects of subanesthetic concentrations of volatile agents on the hypoxic ventilatory response may be related to the conditions under which the subjects were tested. In this study we investigated the effects of 0.1 minimum alveolar concentration (MAC) of isoflurane on the hypoxic ventilatory response without and with audiovisual stimulation. METHODS: Step decreases in arterial hemoglobin oxygen saturation from normoxia into hypoxia (arterial hemoglobin oxygen saturation 80% +/- 2%; duration of hypoxia 5 min) were performed in ten healthy subjects. We obtained four responses per subject: one without isoflurane in a darkened, quiet room; one without isoflurane with audiovisual input (music videos); one in a darkened room at 0.1 MAC isoflurane; and one at 0.1 MAC isoflurane with audiovisual input (subjects were addressed to keep their eyes open). Experiments were performed against a background of isocapnia (end-tidal carbon dioxide tension 1-1.4 mmHg above initial resting values). RESULTS: The hypoxic responses averaged 0.54 +/- 0.09 1.min-1.%-1 (without isoflurane in a darkened, quiet room), 0.27 +/- 0.06 l-min-1.%-1 (in a darkened room at 0.1 MAC isoflurane; P < 0.01), 0.56 +/- 0.131.min-1.%-1 (without isoflurane with audiovisual input), and 0.47 +/- 0.13 l.min-1.%-1 (at 0.1 MAC isoflurane with audiovisual input). Values are means +/- SE. During 0.1 MAC isoflurane administration, all subjects showed a depressed hypoxic response when not stimulated, while with stimulation two subjects had an increased response, four a decreased response and four an unchanged response compared to control. CONCLUSIONS: We observed an important effect of the study conditions on the effects that 0.1 MAC isoflurane has on the hypoxic ventilatory response. A depressant effect of subanesthetic isoflurane was found only when external stimuli to the subjects were absent. With extraneous audiovisual stimuli the effect of isoflurane on the response to hypoxia was more variable. On the average, however, the response then was not depressed by isoflurane.

Acoustic Stimulation↗

PubMed1993

Effects of eseroline on the ventilatory response to CO2.

The effect of eseroline on the normoxic hypercapnic ventilatory response was assessed in nine alpha-chloralose-urethane-anaesthetized cats. The ventilatory responses to step changes in end-tidal PCO2 were determined before (control), during i.v. infusion of eseroline (bolus of 1.2 mg.kg-1 followed by 0.65 mg.kg-1 x h-1) and 1 h after the end of the infusion. Each response was separated into central and peripheral chemoreflexes, characterized by CO2 sensitivity, time constant, time delay and apnoeic threshold. We found that eseroline depressed ventilation by affecting both tidal volume and breathing frequency. The ventilatory response to CO2 was depressed due to a decrease in the CO2 sensitivity of peripheral chemoreceptors from 0.20 to 0.12 l.min-1 x kPa-1 and in the CO2 sensitivity of central chemoreceptors from 1.04 to 0.50 l.min-1 x kPa-1 (P < 0.01). However, the ratio of these sensitivities was not changed, like the apnoeic threshold. The depressant effect was reversed by naloxone. We conclude that the depressant effect of eseroline on ventilatory response to CO2 is mainly due to an action on the respiratory integrating centres in the brainstem rather than on the CO2 sensitivity of peripheral and central chemoreceptors.

Analgesics↗

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↗