K. Berger

Influence of calcium and magnesium on the respiratory response to changes in CSF pH.

Abstract The ventral surface of the medulla oblongata of anesthetized cats was superfused with fluids of different Ca++ and Mg++ concentration and pH. The effects of altered composition of the superfusing fluids on respiration were studied. A three-fold increase of the reference Ca++ concentration (1.5 meq/1) in the fluids was followed by a decrease in the tidal volume and ventilation at pH 7.0, whereas at pH 7.6 an effect on respiration could not be observed. When CSP Ca++ was reduced to 30% of the reference concentration, an increase of respiratory parameters at pH 7.6 followed, while at pH 7.0 tidal volume and ventilation remained unchanged. Lower CSF Ca++ concentrations (0.15 meq/1) had no significant influence on respiration. Removal of Ca++ from the superfusing fluids caused respiratory irregularity which in some cases was accompanied by convulsions of skeletal muscles. Mean tidal volume and ventilation values were reduced. Effects of Ca++ removal were partially neutralized by adding equivalent amounts of Mg++ to the Ca++-free fluids, whereas Mg++ when added to fluids containing physiological amounts of Ca++, had no significant effect on respiration. The possible mechanisms involved in the propagation of Ca++ and Mg++ effects are discussed.

Untersuchungen zum zentralen chemosensiblen Mechanismus der Atmung

SummaryIn cats lightly anesthetized with chloralose-urethane, the respiratory response to changes in the medullary extracellular pH (pHe) was studied before and after cervical vagotomy. pHe was varied by perfusion of the ventral medullary surface with mock CSF of different pH (pHCSF) and by changes inPACO2; it was calculated from the acid-base parameters of the blood and the mock CSF by means of a mathematical model described by Berndt, Berger, and Mückenhoff (1972). Results. 1. The hydrogen ion concentration in the CSF does not influence respiration at pHCSF values below 6.5. 2. An increase of ventilation as a response to increasing extracellular hydrogen ion concentration is only obtained in a pHe range of about 0.2 pH units, which under the conditions of the present experiments lay between pHe 7.1 and 7.3, due to the methods of calculation employed. pHe-values below 7.1 usually caused a decrease in ventilation. 3. Vagotomy influences the response of the tidal volume and the respiratory frequency to changes in pHe: the tidal volume is increased after vagotomy and the slope of the pHe-response curve ofVTis steeper, while the frequency decreases and further diminishes with decreasing pHe. The average response of ventilation, however, is not significantly altered after vagotomy. This confirms the hypothesis that in the case of the central chemical control of respiration the vagal activity is responsible for the partition of the total response to chemical stimuli into partial responses ofVTandf rather than for the magnitude of the total ventilatory response.

Interaction of peripheral and central respiratory drives in cats I. Effects of sodium cyanide as a peripheral chemoreceptor stimulus at different levels of CSF pH

In cats anesthetized with chloralose-urethane, the central respiratory chemoreceptors were exposed to mock CSF of pH 7.02, 7.20, or 7.57. The right carotid body was simultaneously stimulated by intracarotid injections of 40, 80, or 160 μg sodium cyanide in 200 μl Ringer solution. The left carotid nerve and, in some animals, both vagosympathetic truncs were dissected. It could be demonstrated the the increase in ventilation produced by application of NaCN to the peripheral chemoreceptors is significantly larger at high than at low mock CSF pH (i.e. at low than at high central stimulus intensity). In vagotomized cats the responses of VT and gelai to NaCN similarly depend upon CSF pH; they are somewhat larger, though, than in intact animals. These results are discussed as compared with results reported by different authors.

Untersuchungen zum zentralen chemosensiblen Mechanismus der Atmung@@@Studies on the central chemosensitive mechanism of respiration: II. Die Steuerung der Atmung durch das extracellulre pH im Gewebe der Medulla oblongata@@@II. Control of respiration by the extracellular pH in medullary tissue

SummaryIn cats lightly anesthetized with chloralose-urethane, vagal and carotid nerves dissected, the ventral surface of the medulla oblongata was perfused with mock CSF solutions. The pH of the fluids was varied by altering either the bicarbonate concentration or the CO2 pressure. During each period of perfusion steady statePACO2 response curves of respiration were recorded.Tidal volume, respiratory frequency, and ventilation were plotted against a) the alveolar CO2 pressure, b) the pH of the perfusion fluids (pHCSF), and c) the pH in the extracellular space of the medulla (pHe). pHe was calculated from the acid base parameters of the blood and the mock CSF by means of a mathematical model described by Berndt, Berger and Mückenhoff (1972).Under the conditions specified above respiration was neither a unique function ofPACO2 nor of pHCSF. In a single experiment, severalPACO2 response curves could be recorded, the number and position of which depended upon the number and the composition of the fluids simultaneously applied to the medullary surface. Similarly, pHCSF response curves could be constructed, the position and course of which was determined by thePACO2.On the other hand, respiration could be shown to be an almost unique function of the medullary extracellular pH—irrespective of whether pHe was changed by alteringPACO2 or pHCSF—ifVT or  were platted against the pHe values located at a depth of 200–400 μm below the ventral medullary surface. A worse correlation was obtained between respiration and pHe at smaller or greater depth.It is concluded that the effects on respiration of changes in the CO2 pressure of the blood or in the bicarbonate concentration and the CO2 pressure of the CSF can be explained by their influence on the extracellular hydrogen ion concentration in the medulla. The chemosensitive structures responding to the hydrogen ion concentration have to be assumed at a location less than 1 mm below the ventral medullary surface.

Influence of potassium on the respiratory response to changes in CSF pH

Abstract The ventral surface of the medulla oblongata of anesthetized cats was superfused with mock CSF of different K + concentration and pH. The effects of the potassium concentration on the respiratory response to pH changes were studied. 50.0 meq/1 K + in the superfusing fluid cause respiratory arrest. This effect does not depend on the pH of the mock CSF. 15.0 meq/1 K + stimulate respiration. This excitatory action is strong at alkaline mock CSF pH (pH 7.6) and less pronounced at acid values (pH 7.0). Thus the differences between Vt or e at acid and at alkaline CSF pH values are diminished and as a consequence the respiratory sensitivity to changes in the CSF pH is reduced, when [k + Csf is elevated to 15.0 meq/1. The stimulatory effect of 15.0 meq/1 K + on respiration and the depressant effect on the respiratory sensitivity to pHcsp changes are not abolished by a simultaneous increase of [Ca ++ lcsr. No significant influence on respiration is observed during superfusion with fluids of decreased K + content (1.5 and 0.5 meq/1). Removal of potassium from the mock CSF is followed by diminished respiration. The possible mechanisms involved in the interaction of hydrogen and potassium ions in the stimulation of respiration are discussed.

[Respiratory response to isolated changes of cerebrospinal fluid pH: studies of anesthetized and decerebrate cats before and during vagus nerve blockade].

SummaryThe ventral medullary surface of cats was perfused with mock CSF of different hydrogen ion concentrations (pH 6.5–7.9).PACO2andPCSFCO2were kept constant at about 35 mm Hg throughout the experiments. The curves relating tidal volume, respiratory frequency, and ventilation to pHCSF were determined in lightly anesthetized (chloralose-urethane) and decerebrate animals, before and during vagal blockade.In anesthetized cats respiratory frequency and ventilation were diminished as compared with decerebrate animals while the pHCSF-response curve of tidal volume was almost the same in both cases.The influence of vagal activity on the pHCSF-response curves of respiration was the same in decerebrate and in anesthetized cats: vagotomy caused an increase in tidal volume and a decrease of respiratory frequency in the whole range of pHCSF studied in the experiments. Ventilation, however, remained almost unchanged.In the vagotomized animal the ventilatory response to changes in pHCSF was due to a reaction of tidal volume only, while both tidal volume, and respiratory frequency contributed to the ventilatory response if the vagal nerves were intact.Vagotomy linearized the response curves of tidal volume and ventilation mainly by increasing the slopes of these curves in the low pHCSF range. This effect was statistically significant in decerebrate cats in the case of tidal volume but less pronounced in the case of ventilation and in anesthetized animals.As far as the central chemosensitive mechanism is concerned, no influence of vagotomy on the sensitivity of the respiratory control system could be found. However, the nature of the ventilatory reactions to chemical stimuli, i.e. the ability to respond by changes in both tidal volume and frequency, depends upon the integrity of the vagal nerves.ZusammenfassungDie ventrale Oberfläche der Medulla oblongata von Katzen wurde mit künstlichem Liquor cerebrospinalis unterschiedlicher Wasserstoffionenkonzentration (pH 6,5–7,9) überströmt. Alveolärer CO2-Druck (PACO2)und CO2-Druck des künstlichen Liquors (PCSFCO2)wurden bei etwa 35 Torr konstant gehalten. Die Abhängigkeit des Atemzugvolumens, der Atemfrequenz und der Ventilation vom Liquor-pH (pHCSF) wurde an mit Chloralose-Urethan flach narkotisierten und an dezerebrierten Tieren vor und während Vagusblockade ermittelt.Bei anaesthesierten Katzen waren im Vergleich zu dezerebrierten Tieren Atemfrequenz und Ventilation vermindert, während die pHCSF-Antwortkurve des Atemzugvolumens in beiden Fällen nahezu den gleichen Verlauf zeigte.Die Vagusaktivität hatte auf die pHCSF-Antwortkurven der Atmung sowohl bei dezerebrierten wie auch bei anaesthesierten Tieren einen ähnlichen Einfluß: Vagotomie verursachte eine Zunahme des Atemzugvolumens und eine Abnahme der Atemfrequenz. Die Ventilation dagegen zeigte sich nicht deutlich verändert.Beim vagotomierten Tier waren die Antworten der Ventilation auf Änderungen im pHCSF allein auf Änderungen des Atemzugvolumens zurückzuführen, während sowohl Atemzugvolumen als auch Frequenz zur Atmungsantwort beitrugen, solange die Vagusnerven intakt waren. Vagotomie führte zu einer Begradigung der Antwortkurven des Atemzugvolumens und der Ventilation, vorwiegend über eine Zunahme der Anstiegssteilheit dieser Kurven im Bereich niedriger pHCSF-Werte. Dieser Effekt war bei dezerebrierten Tieren im Fall des Atemzugvolumens statistisch zu sichern. Im Fall der Ventilation und bei anaesthesierten Tieren war erweniger deutlich ausgeprägt. Ein Einfluß der Vagotomie auf die Empfindlichkeit des zentralen chemosensiblen Mechanismus konnte nicht festgestellt werden. Dagegen ist die Art der Atemantwort auf chemische Reize, d. h. die Fähigkeit, durch Veränderungen des Atemzugvolumens als auch der Atemfrequenz zu reagieren, von der Unversehrtheit der Nn. vagi abhängig.