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R L Martin-Body

Publications and source records attributed to R L Martin-Body.

10 recordsLinked to original sources

Central origin of the hypoxic depression of breathing in the newborn.

These studies were designed to ascertain whether the mechanism underlying the depressive component of the response to hypoxia in the newborn is similar to that in the fetus. We studied the response to hypoxia in 5-10 day old unanaesthetized rabbit pups before and after decerebration at or near the level of the midbrain/pontine junction. In the intact animal, hypoxia caused an initial stimulation of minute volume (VE) followed by a depression which was due to a decrease in both tidal volume (VT) and respiratory frequency (f). Decerebration abolished the depressive component of the response; the initial increase in VE on exposure to 7% O2 was now maintained, mainly due to a sustained increase in VT. We conclude that there is a central mechanism sited in or above the upper pons which is involved in the depressive component of the biphasic response to hypoxia. It is likely that this mechanism is similar to that mediating the hypoxic depression of breathing in the fetus.

Animals↗

Brain transections demonstrate the central origin of hypoxic ventilatory depression in carotid body-denervated rats.

1. The characteristics of hypoxic ventilation were studied in awake adult rats after brain transections about the intercollicular level. The results were compared with studies made before transection, 17-24 h after bilateral carotid body denervation effected by carotid sinus nerve section. 2. Transection at or below the intercollicular level converted the depressive hypoxic frequency response of control studies to a stimulatory response, increased the stimulation of tidal volume by hypoxia, and so converted the dominant pattern of ventilation in hypoxia from a depression to a progressive stimulation. 3. Transection above the intercollicular level failed to reverse the hypoxic frequency response but increased the stimulation of tidal volume by hypoxia. Consequently minute ventilation progressively increased as the severity of hypoxia increased. 4. The experiments demonstrate that in the adult rat depression of respiratory frequency by hypoxia after carotid body denervation requires the integrity of a region at or immediately above the intercollicular level. In contrast, the stimulation of tidal volume by hypoxia is markedly dependent upon precollicular structures. 5. The results are discussed in relation to the hypoxic depression of fetal breathing and the biphasic hypoxic ventilatory response of the newborn.

Animals↗

Morphological properties of respiratory intercostal motoneurons in cats as revealed by intracellular injection of horseradish peroxidase.

This study was undertaken to describe details of the location and cellular morphology of functionally identified (inspiratory or expiratory) external and internal intercostal motoneurons on the basis of intracellular injection of horseradish peroxidase (HRP). Sixty HRP-labeled motoneurons were examined; 44 in transverse, 16 in sagittal sections. In the upper thoracic segments (T3-T4), there was only a small overlap in the location of inspiratory external and internal intercostal motoneurons; the inspiratory external motoneurons were generally found more ventromedially within the ventral horn than either inspiratory or expiratory internal intercostal motoneurons. No major morphological differences were observed between the types of motoneurons studied. The number of primary dendrites ranged from 6 to 10. The dendrites projected mainly along the medial or the lateral border of the ventral horn, and rostrocaudally up to 1,760 micron from the cell body. The paths taken by dendrites to fill the territory occupied by the dendritic trees appeared to depend upon location of the cell body. Few dendrites penetrated the white matter. Axon diameters varied from 1.1 to 6.7 micron (mean 3.6 +/- 1.3 micron, n = 55). Collateral branches were identified in 78% of axons. The number of branches arising from a given axon varied from 1 to 4. It is concluded that the respiratory intercostal motoneurons form a morphologically homogeneous population, in spite of their functional differences.

Animals↗

Differences in respiratory patterns after acute and chronic pulmonary denervation.

The role of pulmonary vagal information in the control of respiratory patterns was assessed in awake and anaesthetised rats in which pulmonary denervation was effected by bilateral cervical vagotomy or by right cervical vagotomy combined with left pneumonectomy or left intrathoracic vagotomy. Acute denervation led to increases of tidal volume (VT), inspiratory duration (TI) and expiratory duration (TE) in both awake and halothane anaesthetised animals; in awake rats the increase of TE rapidly subsided. Chronic pulmonary denervation produced markedly smaller increases of VT and TI and no change of TE from control values. In hypercapnia, awake animals with combined pneumonectomy and vagotomy consistently increased respiratory frequency by reductions in TI and TE; awake animals with combined intrathoracic and cervical vagotomy showed no increase in f because decreases in TI offset increases in TE; in anaesthetised rats with acute bilateral cervical vagotomy there was a consistent fall in respiratory frequency due to an expiratory pause. The results demonstrate that (1) the role of vagal activity in the production of respiratory patterns is unlikely to be accounted for solely in terms of influences arising from pulmonary stretch receptors; (2) vagal influences of TE are transitory; (3) under halothane anaesthesia hypercapnia induces an expiratory pause; and (4) the combination of pneumonectomy with contralateral vagotomy makes possible studies in awake rats although pulmonary denervation is less complete than with bilateral intrathoracic vagotomy.

Animals↗

Brain stem projections of the glossopharyngeal nerve and its carotid sinus branch in the rat.

Transganglionic transport of horseradish peroxidase or lectin-conjugated horseradish peroxidase from an application site in the cervical trunk of the glossopharyngeal (IXth cranial) nerve of the rat produced extraperikaryal reaction product characteristic of axon terminal processes in three regions of the brain stem: (1) the nucleus of the tractus solitarius, from approximately 2.5 mm rostral to the obex to approximately 3 mm caudal to the obex; (2) the spinal trigeminal nucleus at the level of obex; (3) the cuneate fasciculus, approximately 3 mm caudal to the obex. In contrast, labelling of the carotid sinus nerve, a branch of the glossopharyngeal nerve which conveys chemoreceptor and baroreceptor afferent fibers from the carotid bifurcation, revealed a restricted central projection to within 1 mm of the obex and corresponding to the intermediate region of the glossopharyngeal nerve projection to the nucleus of the tractus solitarius. Two distinct aggregations of label were observed: (1) rostral to the obex, within the lateral and dorsomedial subnuclei of the nucleus of the tractus solitarius; (2) caudal to the obex, within the commissural and ventrolateral subnuclei of the nucleus of the tractus solitarius. Between these two sites the density of labelling was reduced. Retrogradely labelled neurons were demonstrated in the inferior salivatory nucleus and in the nucleus ambiguus after application of lectin-conjugated horseradish peroxidase to the glossopharyngeal nerve. Of the labelled neurons in the nucleus ambiguus (approximately 100), 25% contributed fibers to the carotid sinus nerve. The concentration of extraperikaryal reaction product located rostral to the obex after labelling of the carotid sinus nerve closely matches descriptions of the region of afferent terminations from carotid and aortic baroreceptors in the cat. The concentration of label caudal to the obex may therefore correspond to the region of afferent terminations from carotid chemoreceptors. This study may therefore provide some basis for a separation of the central synapses of primary afferent fibers from the carotid baroreceptors and chemoreceptors in the rat. The labelled neurons of the nucleus ambiguus provide the anatomical substrate for centrifugal control of carotid chemoreceptor activity.

Afferent Pathways↗

Restoration of hypoxic respiratory responses in the awake rat after carotid body denervation by sinus nerve section.

The restoration of ventilatory responses to hypoxia after carotid body denervation was studied in twenty-eight awake rats. The respiratory depression seen in moderate hypoxia (partial pressure of inspired O2, PI,O2, 80-100 mmHg) 3 days after bilateral carotid sinus nerve section disappeared by day 10. By day 17 respiratory stimulation occurred at all levels of PI,O2 below 125 mmHg. The largest restored response, in severe hypoxia (PI,O2 50-60 mmHg), was approximately 55% of the pre-denervation response. The response showed little further change from day 17 to day 192. A comparison of the effect of bilateral section of the glossopharyngeal nerve and of the abdominal vagus 1 and 28 days after carotid sinus nerve section demonstrated that the restoration of hypoxic response resulted in part from an enhanced effect of the inputs from the secondary glomus tissue served by these nerves. A comparison of the effect of bilateral section of glossopharyngeal, abdominal vagal and aortic depressor nerves 1 and 28 days after carotid sinus nerve section demonstrated an increase of a residual hypoxic response which must result either from inputs from unidentified peripheral chemoreceptors or from central mechanisms. Bilateral sectioning of the aortic depressor nerves produced no additional effect on restored responses to sectioning glossopharyngeal and abdominal vagal nerves, providing further evidence against significant aortic body function in the rat. The studies support the hypothesis that central neural reorganization provides compensation for loss of carotid body function by enhancement of effects of normally subsidiary inputs.

Abdomen↗

Analysis of respiratory patterns in the awake and in the halothane anaesthetised rat.

Respiratory patterns have been studied in awake and halothane anaesthetised rats. Tidal volume (VT) was shown to be age-sensitive over 44-200 days; failure to account for this gave the appearance of an increased ventilatory sensitivity to CO2 with age. Inspiration of CO2 (0-10.5%) produced linear responses of VT whereas frequency responses stabilised at 6% CO2. Initially expiratory duration (TE) decreased more than inspiratory duration (TI) and both decreased linearly relative to increased VT; above 6% CO2, increases in VT occurred with only minor changes in TI and TE. Halothane anaesthesia dominantly depressed the frequency response to CO2. We conclude that the rat shows a great influence of vagal control on breathing in the awake state and in halothane anaesthesia; that TE is controlled independently of TI; and that respiratory frequency is more rigorously controlled than VT.

Aging↗

Respiratory effects of sectioning the carotid sinus glossopharyngeal and abdominal vagal nerves in the awake rat.

Normoxic and hypoxic respiration has been measured in awake rats after denervation procedures designed to eliminate the regulatory input from the carotid bodies, from all chemosensory tissue supplied by the glossopharyngeal nerve (n. IX), and from abdominal chemoreceptors. Studies were made 1 day after section of the carotid sinus nerve (c.s.n.), n. IX (at a level including c.s.n.), the abdominal vagus (n. Xa) and combinations of these nerves. Results were compared with those found in normal controls. C.s.n. section led to hypoventilation in both normoxia and hypoxia, reductions in respiratory frequency being consistent and substantial, and reductions in tidal volume varying with the degree of hypoxia. By comparison, section of n. IX produced significantly greater reductions of both normoxic and hypoxic ventilation. Section of n. Xa produced no significant change in normoxic ventilation but in hypoxia produced a significant small reduction in ventilation, mostly from an effect on tidal volume. Denervation of all the associated chemosensory tissue by combined section of n. IX and n. Xa demonstrated a summation of effects but left two distinct residual responses, one to mild hypoxia, and one to severe hypoxia, both associated mainly with increases of tidal volume. The experiments demonstrate that glomus tissues at different sites in the rat produce significant and distinct contributions to respiratory regulation. Denervation of all known receptors shows that significant ventilatory responses to hypoxia are still produced, either by unrevealed peripheral chemoreceptors, or by central neural mechanisms.

Abdomen↗

Effects of urethane-chloralose anaesthesia on respiration in the rat.

1. Respiratory effects were measured in rats during six hours' anaesthesia with urethane and chloralose. 2. One-hundred min from urethane administration, minute ventilation (VE) was minimal, arterial PO2 was low, arterial PCO2 was high; tidal volume (VT) and respiratory frequency (f) were relatively constant; hypercarbic and hypoxic responses were substantial. 3. Between 100 and 400 min from urethane administration, minute ventilation and frequency increased and became more variable, tidal volume remained relatively constant, arterial PO2 rose to 100 mmHg, PCO2 fell to 37 mmHg; hypercarbic sensitivity increased and hypoxic sensitivity decreased. 4. We conclude that the anaesthetic regime produced initial depression of respiration relative to metabolism but without great loss of respiratory chemosensitivity. The respiratory depression was prolonged by increased dosage with urethane and chloralose. 5. The variations between hypercarbic and hypoxic responses confirm that they operate through separate mechanisms.

Anesthesia↗

Effects of neurotoxin-induced brainstem lesions on the respiratory responses of conscious rats.

Respiration was recorded in unanaesthetized rats breathing air, or CO2 in air, 4-8 days after injection into the rostral brainstem at the level of the dorsal raphe nucleus of either a catecholaminergic neurotoxin, a serotoninergic neurotoxin, or the vehicle (0.5% ascorbic acid) of these drugs. Some rats were pretreated with the noradrenergic neurone protecting agent, desmethylimipramine (DMI). Vehicle injection resulted in an increase in the frequency (f) sensitivity to CO2. In two of four cases, injection of 6-hydroxydopamine caused a similar response but in the remaining cases injections caused increases in inspiratory duration (TI), expiratory duration (TE) and tidal volume (VT) during air-breathing. The serotonergic neurotoxin, 5,7-dihydroxytryptamine, reduced the frequency sensitivity to CO2 significantly. This reduction was not sustained. In all cases air-breathing f was decreased due to a prolongation of TI; in most cases air-breathing VT was increased. The characteristic effect of midline 5,7-dihydroxytryptamine lesions was an increase in the VT sensitivity to CO2. On the basis of the results, it is proposed that noradrenaline is essential to the processes determining basic respiratory rhythm, whereas dopamine and serotonin are important inhibitors in chemoreflex ventilatory patterns.

5,7-Dihydroxytryptamine↗