J. De Goede

Relative contribution of central and peripheral chemoreceptors to the ventilatory response to CO2 during hyperoxia.

Using the technique of artificial ponto-medullary perfusion, the steady state ventilation during hyperoxia was measured in 15 anaesthetized cats as a function of the central PaCO2 (PaCO2) and peripheral PaCO2 (PapCO2). To a first approximation the ventilatory response was linearly related to both the central and peripheral arterial carbon dioxide pressures, viz. VE=SC . PacCO2 + Sp . PapCO2 - K where Sc and Sp represent the overall central and peripheral sensitivity to carbon dioxide. The mean ratio Sp/Sc was 0.48 (range 0.21 to 1.08). In carotid sinus denervated cats Sp was zero, while the values of Sc in these cats were in the range of Sc of cats with intact carotid sinus nerves. It is concluded that the peripse to CO2 under steady-state conditions. Chemodenervation experiments revealed that the carotid bodies play an essential role in this contribution.

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.

Influence of peripheral O2 tension on the ventilatory response to CO2 in cats

The effects of peripheral hypoxia on ventilation were investigated in 18 cats anaesthetized with chloralose urethane. The ponto-medullary region of the brain was artificially perfused via a cannulated vertebral artery, using an extracorporeal circuit fed from a femoral artery. In this way the carbon dioxide tension (PacCO2) and the oxygen tension in the blood supplying the brainstem could be imposed independently from the peripheral PCO2 (PapCO2) and PO2 (PapO2) in the systemic circulation. In all experiments the brainstem was kept hyperoxic. The steady-state ventilation VE could be described by (formula; see text) where Sp and Sc represent the peripheral and central sensitivity to carbon dioxide and K is a constant. Sc and K were independent of the PapO2. In general, peripheral hypoxia increased and peripheral hyperoxia decreased Sp, compared to normoxia. It is concluded that: (1) there is no interaction in the ventilatory response between peripheral O2-CO2 and central CO2 stimuli; and (2) a positive interaction in the ventilatory response between peripheral hypoxia and CO2 originates from the arterial chemoreceptors.

The contribution of the peripheral chemoreceptors to the ventilatory response to CO2 in anaesthetized cats during hyperoxia

Abstract Experiments were performed on nine adult cats anaesthetized with chloralose and urethane. The ventilatory response to CO2 during hyperoxia (FlO2) was determined before and after denervation of the peripheral chemoreceptors. We observed flattening of the upper part of the CO2 response curve occurring at lower levels of V e after vagotomy. The part of the V e vs. PaCO2 curve could be described by a linear relation with slope S and intercept B at zero ventilation. In four cats both the slope and B value remained essentially the same after vagotomy. After subsequent sinus neurotomy a reduction in S in the range of 32–46% (mean 41%) was observed with no systematic change in B. In five cats the sequence of the denervation procedures was reversed. After carotid chemodenervation the slope decreased in the range of 23–54% (mean 41%) with no systematic change in B. When subsequent vagotomy was performed the changes in slope were negligible, except for one experiment where a further reduction in slope of 15% was observed. The arterial blood pressure and the stability of the respiratory variables tended to be more affected when both vagotomy and sinus neurotomy were performed. It is concluded from the slope reductions that in the presence of hyperoxia the contribution of the carotid chemoreceptors to the respiratory response to CO2 amounts to about 40%, and that the relative contribution of the aortic bodies to the ventilation is negligible.

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.

Conductance fluctuations in ranvier nodes

SummaryVoltage fluctuations associated with the sodium system were measured upon elimination of the potassium current in the nodal membrane by internal application of cesium-ions. The intensity of this noise reaches a maximal value at a membrane potential in the vicinity of −40 mV. Here the power spectrum consists of two additive components: a 1/f component and a Lorentzian. The Lorentzian is associated with h-gate kinetics and is consistent with the binary state conduction model. On the basis of this model the sodium-channel conductance is calculated to be2 to 5·10−12S. The analysis is complicated by the existence of an incomplete slow sodium inactivation process.

Influence of the CSF bicarbonate concentration on the ventilatory response to CO2 in relation to the location of the central chemoreceptors

In anaesthetized cats, in which the cerebrospinal fluid bicarbonate concentration was varied by a ventriculocisternal perfusion technique, the ventilatory response to CO2 during hyperoxia could be satisfactorily described by VE = S(PCSFCO2 -B). Both the slope S and the intercept B were positively and linearly related to the CSF bicarbonate concentration. Assuming that the PCSFCO2 is equal to the PCO2 in extracellular fluid, it can be shown that VE is a linear, but not a unique function of the [H+] at the site of the chemoreceptors; the slope of this relation varies with the bicarbonate concentration at that site, possibly due to chemical complex formation between HCO-3 and Ca2+ or Mg2+. Changes in the B-value were related to the location of the central chemoreceptors with the models of Pappenheimer and Berndt aand their coworkers. It was found that changes in the CSF bicarbonate concentration are reflected for 60 per cent at the site of the central chemoreceptors, and that this was independent of the cerebral perfusion. Using Berndts model a distance between CSF and central chemoreceptors of approximately 100 micron was found; this calculated distance is relatively insensitive to relationship (logarithmic or not) between ventilation and H+ concentration and to changes in cerebral perfusion, owing to the approximate nature of the diffusion model.

Effect of temperature on the ventilation response curve to carbon dioxide in anaesthetized cats

Effects of body temperature on the ventilatory control system were studied in 17 anaesthetized cats. At different body temperatures (stabilized within 0.1 degrees C) CO2 response curves were measured in each cat. In with chloralose-urethan anaesthetized cats it was found that in the body temperature range of 34-40 degrees C, in which neither shivering nor panting occurred, no statistically significant trend with temperature was found in the slope (S) and the extrapolated intercept on the PaCO2-axis (B) of the linear CO2 response curve during hyperoxia as well as hypoxia. In two with pentobarbital anaesthetized cats similar results were obtained. The resting ventilation (at FICO2 = 0) did not change significantly, while the resting PaCO2 during hyperoxia showed a trend to increase with temperature just reaching the level of significance (P less than 0.05). Breathing frequency increased significantly with temperature (P less than 0.0005). When body temperature was elevated above 41 degrees C both the slope (S) and the intercept of the CO2 response curve (B) decreased. In three cats ventriculo-cisternal perfusion was performed and no apparent influence of body temperature was found on the relation between the PCSFCO2 and PETCO2 and on the VE-PCSFCO2 response curves. These findings show that body temperature has no important modifying effect on the ventilatory response to CO2 in anaesthetized cats in the temperature range of 34-40 degrees C.

The influence of TTX, DNP and TEA on membrane flicker noise and shot effect noise of the frog node of Ranvier

SummaryVoltage noise spectra of the node of Ranvier upon depolarization were investigated in normal Ringer solution and in TTX, DNP, TEA and saccharose Ringer. The intensities of both the 1/f component and the shot effect component of the voltage noise did change in TEA Ringer only. This excludes the sodium channels and active transport as sources of these noises. From considerations of a representation of the potassium and leakage system it follows that leakage as the sole noise source is excluded. The shot effect noise is probably caused by fluctuations of the potassium conductance. For the 1/f noise the behaviour is more complex. Part of it however is due to the potassium system.

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