PubMed HealthSearch

Biomedical subjects

H H Loeschcke

Publications and source records attributed to H H Loeschcke.

At least 19 recordsLinked to original sources

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. It was found that effects of stimulation in expiration were restricted to the expiratory phase, and vice versa for inspiration. Stimulation during both inspiration and expiration resulted in increased VT, by increasing end-inspiratory or decreasing end-expiratory lung volume, respectively, and also increased ventilation, VE. These effects were most marked in response to stimulation in inspiration. During both phases there was an increasing effect with increasing delay of the stimulus, tSt, from onset of inspiration or expiration, respectively. There was a continuous increase in tI, from below control to above control values, with increasing tSt during inspiration and similarly for tE during expiration. Hence, the total respiratory cycle duration was shortened when a stimulus was applied early in either phase, and was prolonged, when it was applied late. The results show that stimulation of peripheral and of central chemoafferents exerts qualitatively similar effects on respiration. The central neuronal mechanisms generating both inspiration and expiration show the same changes in reactivity in the respiratory cycle.

Animals

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. During the recovery phase of VT, the amplitude of phrenic nerve activity returned only partially, whereas the activity of the external intercostal muscle was greater than the prestimulus controls. In a second group of experiments, brief tetanic stimulation at the beginning of inspiration led to a complete and maintained inhibition of phrenic nerve activity but with a simultaneous excitation of external intercostal muscle activity and without any change in VT; whereas expiratory stimulation caused a decrease in expiratory abdominal muscle activity, without changing the peak amplitude of phrenic nerve activity. The respiratory changes observed with distension of the small intestine were abolished after denervation of the mesenteric plexus. It is concluded that activation of the visceral afferents of the mesenteric region reflexly changes diaphragmatic breathing to intercostal breathing. It is assumed that such a type of breathing pattern may occur in pregnancy and in pathophysiological situations involving splanchnic viscera.

Animals

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. Stimulation of peripheral chemoreceptors during cold block remained effective and interrupted apnea in three of the four cats with only aortic chemoreceptors intact. We conclude that the nonchemical vagal respiratory afferents alone are unable to maintain rhythmic ventilation. Respiratory rhythm generation is, under the conditions of our experiments, critically dependent on sufficient afferent input from chemical afferents. Of these, central chemosensitivity plays the major role, followed by carotid body and, least importantly, by aortic afferents.

Afferent Pathways

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.f, VE and pH to such a change in PCO2 were observed. The observations from such a preparation were: 1. pHe responded with a delay of 5-7 s to a rectangular variation in end-tidal PCO2. 2. The time constant of the change in the medullary extracellular pH was in the range of 50 s and a similar value was found for VT and VE. 3. The response of VT or VE to a change in the medullary pHe was approximately linear in anaesthetized as well as in unanaesthetized decerebrate cats. The slope of the respiratory response of VT to pHe in decerebrate cats was about 3 times greater than that in anaesthetized cats. There were only slight differences in the relation of VT to pHe between the transient and steady state responses. This means that the "upstroke" of the on-transient of VT was approximately the same as the 'downstroke' of the off-transient. On the other hand, a slight delay was observed when VE was plotted against pHe. Pronounced delay occurred when respiratory frequency was plotted against pHe for on- and off-CO2 transients. 4. A marked hyteresis was observed when VT or VE was plotted against the cortical pHe for on- and off-CO2 inhalation. 5. Such a precise time correlation of the medullary surface pH and VT changes could only be possible if the pH on the ventral medullary surface is representative for the pH at the sensor.

Anesthesia, General

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. A rapid increase in the brain extracellular bicarbonate concentration was observed in response to an i.v. bolus injection of 3 ml molar NaHCO3. The bolus was followed by a slow infusion of bicarbonate solution. The brain extracellular bicarbonate reached a new steady state within a minute. 2. This increase was almost simultaneously accompanied by a decrease in the extracellular chloride concentration. The HCO-3-Cl- exchange ratio very closely approached one. 3. The extracellular bicarbonate concentration in the brain, after an initial increase, returned towards control in spite of elevated arterial bicarbonate at maintained PCO2. 4. The results are discussed in terms of a 5-compartment model, where the extracellular fluid is interposed between the glial cells and the interstitial side of the endothelial cells, similar to the blood plasma being interposed between the red cells and the luminal side of the endothelial cells. 5. A non-electrogenic carrier-mediated HCO-3-Cl- exchange at the interphase of the blood brain barrier is postulated.

Animals

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. The experiments showed that addition of CO2 caused an increase in the resistance of whole blood, whereas the resistance of separated plasma decreased slightly and the resistance of true plasma remained almost constant. The change in the FPCV (delta H) can be described by a linear function of pH or log pCO2 (formula: see text). The transient response of the resistance, after a stepwise increase in the CO2 content, was found to be the slowest process in attaining an acid-base equilibrium. In blood with acetazolamide, the time courses of changes in pH and pCO2 were retarded, whereas the time course of the resistance change reflecting the swelling of the erythrocytes was nearly the same (T 50 approximately equal to 4 s). This may indicate a rate-limited water shift due to a slight water permeability of the erythrocyte membrane.

Acetazolamide

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). ACh increased the activity of 70% of superficial ventral medullary neurons. Effects of noradrenaline and serotonin on the activity of neurons were largely opposite to that of H+. Cholinergic blocking agents like atropine, hexamethonium and mecamylamine depressed the H+-elicited excitation of neurons. The cholinesterase inhibitor, eserine, increased the neuronal activity. In the presence of eserine, a solution of low pH caused further increase in discharge of most neurons. The low pH solution prolonged and augmented the excitatory action of ACh on the ventral medullary neurons. It is concluded that the H+-elicited excitation of neurons in the "chemosensitive" structures is dependent upon intact cholinergic transmission in the surface layer. This may be interpreted as resulting from facilitation and/or prolongation of such a chemical transmission by H+.

Acetylcholine

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. Acetylcholine (10(-4) g . ml-1 = 5.5 . 10(-4) mMol . ml-1) produced an increase in respiration and a lowering of blood pressure. The magnitude and the time course of the responses varied according to the points of superfusion on the surface. 3. Nicotine (10(-4) g . ml-1 = 6.2 . 10(-4) mMol . ml-1) elicited hyperventilation and more often an increase in arterial pressure on unilateral superfusion of the surface. In some cases, however, a drop in blood pressure was also observed. 4. The responsive regions of the surface on which nicotine acted and elicited hyperventilation, bear a close resemblance to the regions responsive to acetylcholine. 5. The topographical distribution of the respiratory effects elicited by the above-mentioned drugs were similar to the distribution of the responses to changes in pH on the ventral medullary surface or to electrical stimulation. 6. Procaine (2 . 10(-2) g . ml-1 = 7.3 . 10(-2) mMol . ml-1) applied bilaterally in the intermediate zone (S) caused profound inhibition of respiration and of arterial pressure. Procaine at this concentration also inhibited respiratory hyperventilation caused by nicotine (10(-4) g . ml-1 = 6.2 . 10(-4) mMol . ml-1) applied to the caudal and rostral areas.

Acetylcholine

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. 2. The increase of ventilation and the depression of arterial blood pressure by locally applied acetylcholine could be blocked by previous local application of atropine. It is therefore assumed that the acetylcholine receptors have muscarinic properties. 3. Nicotine in a small dose raises arterial pressure and with higher doses a drop is observed. The responses of respiration and of arterial pressure to nicotine were blocked by previous intravenous administration of hexamethonium. 4. Local application of atropine in the caudal (L) and rostral (M) chemosensitive zones reduced resting ventilation and the slope of the ventilatory response to CO2-inhalation. Physostigmine in these areas enhanced resting ventilation leaving unchanged the slope of the ventilatory response to CO2-inhalation. 5. With high concentrations of (L)-noradrenaline and (L)-adrenaline a slight increase of arterial pressure was seen while serotonin caused a drop. 6. These results together with those of Fukuda and Loeschcke (1978) suggest that a cholinergic transmission in the surface layer of the ventral medulla is a component in the respiratory and circulatory control systems.

Acetylcholine

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. In some instances the respiratory frequency was increased by CO2. Periodic breathing as well as spontaneous hyperventilation elicited by 'arousal' indicate parallels to the Pickwickian or Ondine's curse syndrome. No respiratory changes were produced by a lesion on the pyramidal tract medial to the area S. It is concluded that central chemosensitivity can be eliminated within the superficial layer of the area S. The loss of CO2 response seems to be correlated with complete destruction of the superficial nerve cells located within the area S (Petrovický, 1968) and degeneration within the ventral part of the nucleus paragigantocellularis.

Animals

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 7.30 to 7.09, the arterial PCO2 was elevated from 4.80 kPa to 8.17 kPa (6 cats). Ventilation increased by 477 ml at a PCO2a of 6.58 kPa when PO2a was reduced from 39.5 kPa to 8.5 kPa before coagulation, after coagulation ventilation increased by 241 ml (4 cats). The peripheral chemoreceptors guaranteed spontaneous breathing even in hyperoxia. The data reveal that the loss of respiratory homeostasis by elimination of the S areas is due to the loss of central chemosensitive drive with concomitant reduction of peripheral chemoreceptor effect.

Animals

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. Assuming air breathing and a normal critical arterial O2-pressure and otherwise normal parameters of respiration, circulation and blood composition (except diminished buffer base) the central chemosensitivity to a pH change turned out to be 25 times the peripheral. This factor is critically dependent on the ratio of the bicarbonate change in extracellular brain fluid to that in arterial blood. The coinciding data of Fencl (1971) and of Kronenberg and Cain (1968) were used for the calculation.

Acidosis

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. In the dorsal medulla, low pHe caused an inhibition of activity in most neurons, although a few were excited. The fact that H+ elicted excitation predominantly in the ventral medullary substrate to respond to pHe changes. Depression of synaptic transmission within the neuronal network in the slice by reducing the [Ca2+]e and increasing the [Mg2+]e altered the nature of responses of neurons to H+: In the ventral medulla, the majority of neurons were inhibited by H+, whereas in the dorsal medulla more than 50% of neurons were excited. Therefore, "specificity" of the ventral medullary neurons seemed to be dependent upon intact synaptic connections. A possible role of acetylcholine-acetylcholinesterase system in the response of ventral medullary neurons to H+ is discussed.

Action Potentials