Continuous recording of physiological variables and behaviour in young lambs [proceedings].
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Biomedical subjects
Publications and source records attributed to R Harding.
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1. The medulla oblongata of thirteen halothane-anaesthetized, decerebellate sheep was explored systematically with recording micro-electrodes.2. The nervous activity recorded was designated either ;cyclical', if it was related to the periodic vagal outflow responsible for primary cycle movements of the reticulo-rumen, or ;afferent-like', if it was directly related to mechanical stimulation of the reticulum or the abomasum.3. Forms of mechanical stimulation were used which were known (from earlier ;single afferent fibre' studies) to evoke characteristic and distinguishable responses from four receptor types, i.e. reticular tension receptors, reticular epithelial receptors, abomasal tension receptors and abomasal mucosal receptors.4. Micro-electrode penetrations were made within a zone 4 mm lateral to the mid line, 6 mm rostral to and 2.5 mm caudal to the obex. In certain regions, ;afferent-like activity' was recorded, which corresponded to the discharge properties of one or more of the above receptor types.5. Units were sometimes excited or inhibited by more than one kind of receptor excitation, thus demonstrating the possibilities of a convergence of afferent projections and either a direct or a reciprocal relationship between receptor activity and central nervous ;afferent-like activity'.6. It is concluded that most, if not all, of the ;afferent-like activity' was recorded from the vicinity of interneurones.7. There was a partially overlapping viscerotopic organization of ;afferent-like activity' derived from abomasal and from reticular receptors.8. Regions showing ;afferent-like activity' were located dorso-laterally to regions showing ;cyclical activity' although there was some overlap between the two regions.9. ;Afferent-like activity' was recorded from regions which included the dorso-lateral part of the dorsal vagal motor nucleus, the adjacent reticular formation and the nucleus of the solitary tract between transverse planes 3 mm rostral to the obex and 1 mm caudal to the obex.10. Some of the gastric afferent vagal inputs were projected to contralateral locations via unidentified commissural connexions.
1. Responses of identified vagal reticulo-ruminal motoneurones and gastric centre interneurones to changes in vagal afferent activity were examined in anaesthetized, decerebellate sheep.2. Procedures which reflexly modified the form of forestomach movements caused corresponding changes in the activities of motoneurones and Type A interneurones, whereas the activity patterns of Type B, and many Type C, interneurones were not affected.3. Distension of the pyloric region of the abomasum reduced the number of spikes in the periodic discharges of gastric centre neurones (motoneurones and Type A interneurones) with reticular activity, although the frequency of periods of activity was often increased. The afferent pathway for both effects was probably vagal.4. Unilateral vagotomy usually had little effect on the frequency and amplitude of forestomach movements, and did not influence the temporal relation between ipsilateral gastric centre discharges and the movements.5. Median division of the medulla oblongata only in the region between the gastric centres caused a loss of synchronization in the activities of the two centres, indicating the existence of commissural connexions at this level.6. Bilateral vagotomy abolished forestomach movements and motoneuronal activity, but rhythmic activity in gastric centre interneurones continued with a periodicity of approximately 1 min. This persisting periodic activity was unaffected by spinal section, but was not present after transection of the brain stem rostral to the medulla.7. Cyclical gastric centre activity could be elicited by reticular distension in preparations in which the medulla oblongata was isolated from higher regions of the brain, but, in contrast to many sheep in which the brain stem was intact, the existence of the activity was totally dependent upon peripheral afferent activity.8. The evidence indicates that medullary neurones responsible for periodic activation of vagal preganglionic reticulo-ruminal motoneurones may be excited by either or by both vagal afferent fibres from the fore-stomach or by descending, as yet unidentified, influences from the central nervous system.9. Possible roles for gastric centre interneurones in neural networks which control the periodic activation of motoneurones and which control the form of individual activity cycles are discussed.
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1. Neuronal activity bearing a temporal relationship with spontaneous reticulo-ruminal movements was recorded with micro-electrodes from the medulla oblongata in halothane-anaesthetized sheep. Recording sites were located histologically after causing electro-coagulation at the micro-electrode tip.2. One hundred and forty-four gastric units were recorded from the dorsal vagal nucleus and up to 1 mm dorsal and lateral to the nucleus between transverse planes 1 mm caudal, and 4 mm rostral, to the obex. It is considered that records were obtained from the regions of cell bodies.3. The discharges of thirty-two vagal preganglionic motoneurones were identified by an antidromic collision technique. Conduction velocities ranged from 10-26 m/sec. They were located in the dorsal vagal nucleus and up to 0.5 mm dorsal and lateral to the nucleus. The majority of motoneurones innervated either the reticulum or the rumen. One ruminal unit discharged during both primary and secondary cycle movements.4. One hundred and twelve units which were not orthodromically or antidromically activated by stimulating the vagus nerves were considered to be interneurones. Four types were distinguishable on the basis of their patterns of discharge during primary cycle movements.5. The discharges of Type A interneurones resembled those of gastric motoneurones, having no resting discharge between contraction cycles. Their discharges were temporally related to either reticular contractions or rumen contractions during primary and secondary cycle movements.6. Types B and C interneurones have resting discharges which, respectively, increased and either decreased or stopped during each primary cycle movement.7. Discharges of only three units identified as interneurones resembled the discharges of gastric vagal afferent units.
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1. Low birthweight is now recognized as an important risk factor for early postnatal respiratory illness and it is becoming evident that low birthweight can increase the risk for airway dysfunction in children and adults. Our studies have been aimed at determining how low birthweight, resulting from intra-uterine growth restriction (IUGR), affects the control of breathing and the structural and functional development of the lung. 2. We have measured ventilatory responsiveness to progressive hypoxia and progressive hypercapnia during the first weeks after birth in postnatal lambs in which IUGR was induced by chronic placental insufficiency. It was found that the postnatal increase in ventilatory sensitivity to hypoxia observed in control lambs was diminished in low birthweight lambs; in contrast, the sensitivity to hypercapnia was not affected. In other studies, we found that IUGR caused by maternal anaemia led to elevated CO2 levels during sleep and wakefulness. 3. Our findings suggest that the prenatal development of the brain-stem or respiratory chemoreceptors may be affected by intra-uterine factors associated with IUGR, such as foetal hypoxaemia or hypoglycaemia. It is also possible that the structure of respiratory muscles and, hence, their ability to maintain a high level of ventilation may be affected by IUGR. 4. Recently, we studied the influence of IUGR on foetal lung development, in particular its effects on foetal lung liquid, a major determinant of lung growth, as well as alveolar structure and pulmonary surfactant. Lung liquid secretion and volume, in relation to bodyweight, were unaffected; however, there was evidence of structural and functional immaturity in the lungs. In foetuses exposed to IUGR, the air-blood barrier was thicker and, after birth, the diffusing capacity of the lungs for carbon monoxide was lower. In contrast, surfactant protein gene expression was enhanced, particularly in foetuses with high levels of circulating cortisol. 5. Further studies are needed to characterize the effects of specific types of prenatal compromise on postnatal control of ventilation and lung function, to determine mechanisms underlying these effects and to determine the capacity for postnatal recovery.
1. Our aim was to determine the role of nitric oxide (NO) in regulating cerebral blood flow (CBF) in foetal sheep under conditions of both hypoxaemia and normoxaemia. 2. Aseptic surgery was performed on 11 pregnant sheep at 125 +/- 1.1 days of gestational age (g.a.) when foetal vascular catheters were implanted for the measurement of CBF using coloured microspheres. Additionally, each ewe was prepared for one of two procedures for inducing foetal hypoxaemia; either an adjustable clamp was placed around the maternal common internal iliac artery to reduce uterine blood flow, or a catheter was implanted into the maternal trachea for insufflation of N2. At 131 +/- 0.3 days g.a., in control foetuses (n = 5), CBF and cerebral vascular resistance (CVR) were measured under basal (normoxaemic) conditions and after 3h of hypoxaemia. In other foetuses (n = 6) CBF and CVR were measured under basal conditions and after 3 h of hypoxaemia; in these foetuses NO synthesis was inhibited with N-nitro-L-arginine (NOLA) between 2-3 h of hypoxaemia. 3. In the hypoxaemia experiments foetal SaO2 and PaO2 were reduced (P < 0.05) in both control and NOLA-treated foetuses, from normoxaemic values of 69.5 +/- 2.1% and 23.8 +/- 1.0 mmHg, respectively, to 29.3 +/- 1.0% and 14.6 +/- 0.4 mmHg during the period of hypoxaemia. In control foetuses, CBF (mL/min) was increased by 82.7% during hypoxaemia; in NOLA-treated foetuses CBF increased by 55.3%, which was less (P < 0.05) than in control foetuses. In control foetuses CVR (mmHg)/ mL/min) was reduced by 43.5% during hypoxaemia, whereas in NOLA-treated foetuses there was no significant change. 4. In five of the 11 foetuses, the role of NO in regulating CBF under basal (normoxaemic) conditions was determined at 132 +/- 0.3 days g.a. Cerebral blood flow and CVR did not significantly change from basal values after NOLA-treatment. 5. We conclude that in foetal sheep NO plays an important role in regulating cerebral vascular tone and hence CBF during hypoxaemia, but its contribution during normoxaemia is less apparent.