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Biomedical subjects

A Berkenbosch

Publications and source records attributed to A Berkenbosch.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1987

Almitrine bismesylate and the central and peripheral ventilatory response to CO2.

Effects of almitrine bismesylate on the peripheral and central chemoreflex to a CO2 challenge during normoxia were studied in nine alpha-chloralose-urethan anesthetized cats. With the dynamic end-tidal CO2 forcing technique the ventilatory response after a square-wave change in end-tidal PCO2 (PETCO2) was partitioned into a central and a peripheral part using a two-compartment model. With almitrine administered intravenously (0.6 mg/kg followed by a maintenance dose of 0.4 mg.kg-1 X h-1) the CO2 sensitivity of the peripheral chemoreflex increased on the average from 0.315 to 0.564 l.min-1 X kPa-1 (P less than 0.001, 6 cats, 73 runs), whereas the CO2 sensitivity of the central chemoreflex remained the same (P = 0.87). The extrapolated PETCO2 at zero ventilation (apneic threshold) of the (total) steady-state response curve decreased on the average from 3.50 to 2.36 kPa (P less than 0.001). With the artificial brain stem perfusion technique it was confirmed that almitrine did not affect ventilation by administering it to the blood perfusing the brain stem. We conclude that almitrine bismesylate during normoxia enhances the CO2 sensitivity of the peripheral chemoreflex loop and decreases the apneic threshold due to an action located outside the brain stem.

Almitrine↗
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↗
PubMed1986

Response of vertebral and carotid blood flow to isocapnic changes in end-tidal oxygen tension.

The response of the vertebral and carotid blood flow to isocapnic hypoxia was measured in 9 cats anaesthetized with chloralose-urethane using perivascular electromagnetic flow probes. The carotid flow was already significantly increased when going from hyperoxia (PETO2 55 kPa) to normoxia. For the vertebral blood flow a significant increase compared to hyperoxia was observed at a moderate level of hypoxia (PETO2 9 kPa). The time course of the response of the blood flow to isocapnic step-like changes in PETO2 was fitted with a first order model. The mean time constant (+/- SD) for steps into hypoxia for the carotid flow was 35 +/- 38 sec(8 cats) and for the vertebral flow, 44 +/- 37 sec (5 cats). The mean time constant (+/- SD) for steps out of hypoxia was significantly smaller and found to be 23 +/- 22 sec (8 cats) and 19 +/- 18 sec (4 cats), respectively. We argue that a major part of the changes in vertebral and carotid blood flow to steps into hypoxia goes to brain tissue.

Animals↗
PubMed1986

Effects of CO2 and H+ on the ventilatory response to peripheral chemoreceptor stimulation.

To determine whether the stimulatory effect of CO2 on the peripheral chemoreceptors is due to molecular CO2, H+ or both we measured steady-state ventilation (Ve) during normoxia in 9 and during hypoxia in 5 chloralose-urethane anaesthetized cats using the artificial brain stem perfusion technique. This technique allows one to manipulate independently the PaCO2, PaO2 and the pHa of the blood in the systemic circulation (peripheral) and the blood perfusing the brain stem (central). Keeping the central conditions constant the H+ and CO2 concentrations in the systemic circulation were changed by i.v. infusion of 0.3 M HCl or 0.6 M NaHCO3 and by giving the animal different CO2 mixtures to inhale. The peripheral H+ concentration ([H+]p) range covered was from 27 to 103 nmol X 1(-1); the peripheral arterial CO2 tension (PaPCO2) ranged from 2.3 kPa to 8.4 kPa. Fitting the data with the function VE = a[H+]p + bPaPCO2 + c revealed that the coefficient b was not significantly different from zero at the 0.05 level during normoxia and hypoxia. The mean value (+/- SEM) found for the coefficient a was 33.0 +/- 3.6 at normoxia and 36.0 +/- 15.4 ml X min-1 X nM-1 at hypoxia. We conclude that the steady-state ventilatory response due to the stimulation of the peripheral chemoreceptors with CO2 is mediated by H+. The effects of molecular CO2 are negligible.

Acid-Base Equilibrium↗
PubMed1986

A pseudo-rebreathing technique for assessing the ventilatory response to carbon dioxide in cats.

1. The ventilatory sensitivity to CO2 obtained from a non-steady-state step-ramp CO2 challenge (analogous to the Read rebreathing method) was compared with the one of the steady-state method. 2. Experiments were performed during normoxia on twenty cats anaesthetized with chloralose-urethane. In eight of these cats additional measurements were carried out during metabolic acidosis and alkalosis. 3. The slope of the non-steady-state ventilatory response curve to CO2 was not significantly different from the steady-state one only if the ratio of the step-wise increase in end-tidal PCO2 (PET,CO2) (A) above its resting value and the subsequent rate of rise of the PET,CO2 (R) was equal to the time constant of the central chemoreflex pathway (tau c). This also held true during metabolic acidosis and alkalosis. 4. It is predicted that in human beings during hyperoxia the ventilatory response line obtained with Read's rebreathing method is to a fair approximation shifted to the right by a value of A with respect to the steady-state response line, provided A/R = tau c. 5. We argue that Read's prescription that a PET,CO2 equilibrium should be established between mixed venous blood, arterial blood and end-tidal gas has to be regarded as an experimental condition leading to stable-experiments rather than dictated by physiological mechanisms.

Acidosis↗
PubMed1985

Effects of halothane on the ventilatory response to hypoxia and hypercapnia in cats.

The influence of halothane 0.8-1.2% inspired on the peripheral hypoxic chemoreflex was investigated in 13 cats subjected to artificial brain stem perfusion (ABP). This technique allows for an independent control of blood gas tensions and halothane concentration between blood perfusing the brain stem (central) and the systemic circulation (peripheral). In six cats the ventilatory response to isocapnic hypoxia was assessed during overall halothane anesthesia (HO) before and during ABP. Before ABP, systemic and brain stem circulations both were rendered hypoxic. During ABP, hypoxia was induced systemically while the brain stem was maintained hyperoxic. The ventilatory response in non-ABP cats (mean 698 ml . min-1 at PaO2 6.6 kPa; 50 mmHg) was about half the response in ABP cats (mean 1,194 ml . min-1 at PaO2 6.5 kPa; 49 mmHg), indicating that in the presence of halothane, central hypoxia depressed ventilation appreciably. Compared with chloralose-urethane anesthesia (CU), halothane reduced the ventilatory response to hypoxia in both perfusion conditions but never abolished it. To assess the influence of halothane on peripheral and central mediation of the CO2 response during hypoxia, each was assessed during CU anesthesia, during HO, and with halothane applied exclusively peripherally against a background of CU (CUHP). In all drug states, the periphery was kept hypoxic and brain stem hyperoxic. Compared with CU anesthesia, HO and CUHP anesthesia reduced both peripheral (Sp) and central (Sc) CO2 sensitivity but not the Sp/Sc ratio. Similarly, the extrapolated PaCO2 at zero ventilation was not detectably different among these three states.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1985

Comparison of chemoreflex gains obtained with two different methods in cats.

This study investigates the correspondence between results of the ventilatory response to CO2 obtained using the technique of dynamic end-tidal CO2 forcing (DEF) and results obtained using the technique of artificial brain stem perfusion (ABP). The DEF technique separates the dynamic ventilatory response into a slow and fast component with gains g1 and g2 as well as the extrapolated CO2 tension at zero ventilation (Bk). The ABP technique results in steady-state central (Sc) and peripheral (Sp) chemoreflex gains and extrapolated CO2 tension at zero ventilation (B). Experiments were performed on 14 alpha-chloralose-urethan anesthetized cats. A wide range of relative peripheral chemosensitivities was obtained by subjecting eight cats to normoxic and three cats to hypoxic CO2 challenges and three cats to both conditions. Statistical analysis of the experimental data showed that the vectors (g1, g2, Bk) and (Sc, Sp, B) for each cat did not differ significantly (P = 0.56). This was also the case for the vectors [g2/(g1 + g2), Bk] and [Sp/(Sc + Sp), B] (P = 0.21). We conclude that in the DEF experiments the slow ventilatory response to isoxic changes in end-tidal CO2 can be equated with the central chemoreflex loop and the faster ventilatory response to the peripheral chemoreflex loop. The agreement between the two techniques is good.

Animals↗
PubMed1984

Effects of brain stem hypoxaemia on the regulation of breathing.

In 22 cats, anaesthetized with chloralose-urethane, the brain stem was artificially perfused with their own blood via a gas exchanger in which the central PaO2 and PaCO2 were imposed independently from the peripheral PaO2 and PaCO2 in the systemic arterial blood. The effects of brain stem hypoxaemia on ventilation and on the ventilatory responses to central and peripheral chemoreceptor stimulation were investigated. When the central PaO2 was lowered from 375 mm Hg to 100 and 50 mm Hg, keeping all other blood gas tensions constant, ventilation decreased on the average by 0.22 L X min-1 and 0.54 L X min-1, respectively. The increase in ventilation due to peripheral hypoxaemia and the sensitivities to central and peripheral CO2 (delta VE/delta PaCO2) were independent of the central PaO2, despite the depression of ventilation. The sensitivity to central CO2 was also not influenced when central hypoxaemia was combined with peripheral hypoxaemia. The linear VE-VT relation was not affected by central hypoxaemia. Our findings suggest that the functioning of respiratory neurons in the brain stem is unaltered during moderate central hypoxaemia.

Animals↗
PubMed1984

Central respiratory CO2 sensitivity at extreme hypocapnia.

In 7 cats anaesthetized with chloralose-urethane the ponto-medullary region was artificially perfused with blood having PaCO2 values (central PaCO2) in the range of 0.3-4.5 kPa. The ventilatory response to changes in central PaCO2 was measured at constant hypercapnic and hypoxic conditions in the systemic circulation. Ventilation decreased upon lowering the central PaCO2 down to values of 0.5 kPa. There was no threshold for the effect of the central PaCO2 on ventilation. The CO2 sensitivity was undiminished at extreme hypocapnia compared to eucapnia. Under extreme central hypocapnic conditions the breathing pattern became irregular. It is concluded that there is still central CO2 sensitivity related to ventilation at extreme hypocapnia. Our findings suggest that central chemosensitive structures have a neural threshold below a PaCO2 of 0.5 kPa.

Animals↗