Altered breathing pattern elicited by stimulation of abdominal visceral afferents.

The effect of stimulation of afferent mesenteric nerves on tidal volume (VT), phrenic nerve, and external intercostal muscle activities was studied in anesthetized spontaneously breathing cats. Both mechanical distension of the small intestine and electrical stimulation of the mesenteric nerves resulted in an initial inspiratory inhibition of VT followed by a gradual recovery above the prestimulus controls. Changes in VT were accompanied by a depression of phrenic nerve activity and an excitation of external intercostal muscle activity.

Electrical stimulation of arterial and central chemosensory afferents at different times in the respiratory cycle of the cat: I. Ventilatory responses.

Ventilatory responses to stimulation of chemoreceptor afferents were studied in the anesthetized, spontaneously breathing cat. Short bursts of electrical stimuli were applied, at various times in the inspiratory or expiratory phase of consecutive breaths, to the carotid sinus (CSN) and aortic nerves (AN) and to the ventral medulla (VM), and effects on tidal volume (VT), inspiratory, expiratory and cycle durations (tI, tE, ttot) and in ventilation (VE) were measured. The responses evoked by stimulating CSN, AN and VM were qualitatively the same, although there were quantitative differences.

Role of chemical afferents in the maintenance of rhythmic respiratory movements.

In seven anesthetized cats central chemosensitivity was eliminated (cold block) and peripheral chemoreceptors were either stimulated or eliminated (sectioned) to test whether nonchemical vagal afferents can maintain rhythmic ventilation and to determine the relative contribution of the carotid and aortic chemoreceptors to ventilatory drive without central chemosensitivity. Elimination of all chemical afferents invariably induced apnea, whereas ventilation was reduced from 533 to 159 ml X min-1 during cold block of central chemosensitivity and to 478 ml X min-1 after sectioning both sinus nerves. Cold block with only the aortic chemoreceptors and vagal afferents intact produced apnea in four of six cases tested.

Fast bicarbonate-chloride exchange between brain cells and brain extracellular fluid in respiratory acidosis.

The extracellular pH, PCO2, and [Cl-] at the surface of the brain cortex, expiratory PCO2 and arterial blood pressure were continuously recorded in anaesthetized and artificially ventilated cats. The observations from such a preparation were: 1. In response to a nearly step increase in end-tidal PCO2, the brain ECF pH, PCO2, [Cl-] and calculated [HCO-3] changed in the form of a nearly mono-exponential time function after a delay of 5-7 s.

Fast bicarbonate-chloride exchange between plasma and brain extracellular fluid at maintained PCO2.

The aim of this paper was to investigate the kinetics and mechanism of bicarbonate exchange at the blood-brain ECF barrier. The experiments were performed on anaesthetized and artificially ventilated cats in such a way that acid-base parameters of the brain extracellular fluid were continuously measured while an approximately rectangular increase in the arterial plasma bicarbonate concentration was produced at maintained PCO2. The results from such a preparation were: 1.

Transient and steady state responses of pulmonary ventilation to the medullary extracellular pH after approximately rectangular changes in alveolar PCO2.

The extracellular pH (pHe) either on the ventral surface of the medulla oblongata or the parietal cortex, the tidal volume, the expiratory PCO2 and the arterial blood pressure were continuously recorded in anaesthetized or unanaesthetized decerebrate cats. The concentration of the inspired CO2 was manipulated in order to obtain a nearly rectangular increase in the end-tidal PCO2. The responses of VT.

The influence of changes in pCO2 on the fractional packed cell volume of whole blood.

In order to investigate the influence of changes in pCO2 on the fractional packed cell volume (FPCV, hematocrit) of whole blood, a device for measuring the conductivity was developed. This method allows an instantaneous and continuous determination of the FPCV, because the erythrocyte membrane has insulating properties, and, consequently, the resistance of blood depends on the relative cell volume. The steady state and transient relationships between FPCV and acid-base levels were investigated by combining this method with simultaneous recordings of pCO2.

Respiratory response to hypoxia and hypercapnia after elimination of central chemosensitivity.

Central respiratory drive responding to pH changes was eliminated by bilateral coagulation or cold block of area S (intermediate area) on the ventral medullary surface in 7 anaesthetized cats. Arterial pH, PCO2, and PO2 (4 cats) and the respiratory response to hypoxia and hypercapnia (6 cats) were observed before and after coagulation. After coagulation in hyperoxia the arterial pH dropped from 7.

A cholinergic mechanism involved in the neuronal excitation by H+ in the respiratory chemosensitive structures of the ventral medulla oblongata of rats in vitro.

The mechanism of neuronal excitation by H+ in the medullary chemosensitive structures was analyzed in brains slices of the rat in vitro. Responses of neurons to H+ in the ventral surface layer were compared with responses to various transmitter substances. Neurons excited by H+ were always also excited by acetylcholine (ACH).

A cholinergic mechanism involved in the respiratory chemosensitivity of the medulla oblongata in the cat.

1. Cholinomimetic and adrenomimetic substances were tested on the chemosensitive zones of the ventral surface of the medulla oblongata using a plexiglas ring method. Tidal volume and respiratory frequency, arterial pressure and heart frequency were observed.

Topography of the respiratory and circulatory responses to acetylcholine and nicotine on the ventral surface of the medulla oblongata.

1. Acetylcholine and nicotine were superfused on the ventral medullary surface between the ponto-medullary border and C1 in anaesthetized cats in order to determine the topical distribution of their actions on respiration and circulation. 2.

Elimination of central chemosensitivity by coagulation of a bilateral area on the ventral medullary surface in awake cats.

Breathing and respiratory response to CO2 were observed in 6 awake cats and 1 control before and after bilateral coagulation of the formerly described area S (Schläfke and Loeschcke, 1967) on the ventral medullary surface under hyperoxic conditions. Ventilation decreased, PCO2 rose and CO2 response was almost or completely abolished in 4 cats, and moderately reduced in 2 cats. Inhalation of CO2 had an inhibitory effect on ventilation in two cases.

Cooperation of peripheral and central chemosensitive mechanisms in the control of the extracellular pH in brain in non-respiratory acidosis.

The mathematical model of the respiratory control system in man of Middendorf and Loeschcke (1976 a, b) opens the possibility to stimulate the constellation of parameters in non-respiratory acidosis. Several investigators agree that the pH in CSF or in the extracellular fluid of the brain stays remarkably constant in this situation and it can be shown that this is a result of a precise control rather than the consequence of a sluggishly reacting system. Application of the model assuming constant extracellular brain pH allowed to calculate the relative sensitivities to pH changes of the central and the peripheral sensory mechanisms generating respiratory drive.

Effect of H+ on spontaneous neuronal activity in the surface layer of the rat medulla oblongata in vitro.

The effect of changing extracellular pH (pHe) on the spontaneous activity of neurons in brain slices taken from the ventral layer of the rat medulla oblongata was compared to the response of neurons in dorsal slices. In the ventral medulla, more than 50% of the neurons were excited by H+. These neurons were found just lateral to the pyramidal tract between the root of the hypoglossal nerve and the trapezoid body.

[Recent concepts of respiratory regulation (author's transl)].

There are two functional aspects of the respiratory control system, the one being adaptation of ventilation to metabolic needs and the other acid-base homeostasis of the extracellular fluid of the brain. These two functions are perfectly compatible with one another under normal conditions. During hypoxia or hyperthermia, however, a compromise has to be reaches by the system between securing oxygen availability or homeothermy, respectively and acid-base homeostasis of the brain.

[Mathematical simulation of the respiratory system (author's transl)].

The respiratory system is described as a feedback control system. The controller consists of the peripheral chemoreceptors and the central chemosensitive structures, the respiratory centre in the medulla oblongata and the thorax-lung pump which they drive. The controlled system is comprised of three compartments (lung, brain and the remaining tissue) connected by the blood circulation.

Chemosensitive neurons on the ventral medullary surface.

Central chemosensitivity is ascribed to three areas on the ventral medullary surface. The discharge frequency of neurons observed in these areas depends upon pH. Other neurons within the same areas do not change their frequency during acidosis or alkalosis.