Extravagal respiratory reflex from pulmonary nociceptors

A restricted damage of the lung parenchyma before vagotomy evokes an increase of inspiratory discharges of the diaphragm and an increase of the rate of respiration. Similar damage in vagotomized animals evokes only an increase of inspiratory discharges. The rate of respiration does not alter at all or changes insignificantly. An increase of the depth of respiration evoked by the lung nociceptors innervated by the extravagal afferents is of great importance because the lung ventilation is best provided by deep respiration. Probably not only the afferent fibers of the vagus nerves, but also the extravagal lung afferents must be taken into consideration in analysis of the relationship between the rate and depth of lung ventilation, particularly under pathological conditions.     

Role of water receptor in the frog

To elucidate the role of the water receptor in the frog (Rana catesbeiana), reflex activities elicited by its excitation were studied. Application of tap water to the oral mucosa depressed the rhythmical movement of gorge (buccal) respiration, accompanied by an elevation of the inner pressure of the oral cavity (buccal pressure). Tonic reflex discharges were elicited in the nerves innervating the submental and submaxillary muscles, which close the nostrils, the pterygoid and the profound portion of the major masseter muscles, which produce a strong bite, and the geniohyoid and hyoglossus muscles, which elevate buccal pressure. These muscles, except for the pterygoid, also participate in the rhythmical movement of gorge respiration as expiratory muscles. Rhythmical movements in the minor masseter and sternohyoid muscles, which act as inspiratory muscles in gorge respiration, were depressed by the water stimulation of the oral mucosa. These findings indicate that the water receptor plays a role in the interruption of gorge respiratory movements, accompanied by an elevation of buccal pressure.     

腺苷A1受体在离体延髓脑片上对节律性呼吸的调制

实验旨在探讨腺苷A1受体在对基本呼吸节律调制中的可能作用。制作新生大鼠离体延髓脑片标本,主要包含面神经后核内侧区(themedial region of the nucleus retrofacialis,mNRF),并保留完整的舌下神经根。以改良Kreb‘s液灌流脑片,记录mNRF吸气神经元的电活动,并同步记录舌下神经根呼吸节律性放电(respiratory rhythmical discharge activity,RRDA)。在灌流液中先分别单独给予腺苷A1受体的特异性拮抗剂8-环戊-1,3-二丙基黄嘌呤(8-cyclopenty 1-1,3-dipropylxanthine,DPCPX)和特异性激动剂R-苯异丙基-腺苷(R-phenylisopropyl-adenosine,R-PIA);再分别先后给予R-PIA和R-PIA DPCPX,观察RRDA和吸气神经元电活动的变化。结果显示,给予腺苷A1受体拮抗剂DPCPX后,呼气时程和呼吸周期明显缩短,吸气神经元中期放电的频率和峰频率显著增大;给予腺苷Al受体激动剂R-PIA后,吸气时程、积分幅度和吸气神经元中期放电的频率和峰频率均显著降低,呼吸周期明显延长,且R-PIA的呼吸抑制作用可部分地被DPCPX逆转。实验结果提示,腺苷A1受体可能通过介导吸气神经元的抑制性突触输入参与节律性呼吸的调制。     

Resistive loading and mechanisms regulating respiration

In experiments on anesthetized cats, switch on of additional inelastic respiration resistance (resistive load) produced, apart from slowing of the respiratory flows, an increase in the activity of motoneurons and inspiratory intrathoracic pressure. Bilateral vagotomy resulted in disappearance of resistive load-induced elevation of the phrenic nerve activity, but did not abolish the growth of the inspiratory effort. Analysis of the evidence obtained indicates that activation of phrenic motoneurons associated with increased respiration resistance is underlain by prolongation of the inspiratory phase that is consequent on relaxation of the inspiratory inhibition. It is suggested that, in addition to the mechanism depicted, the compensatory reaction to the resistive load involves, apart from diaphragm participation, other inspiratory muscles as well as enhanced contractions of respiratory muscles provided by the properties of muscular fiber.     

Mu-opioid receptor agonist effects on medullary respiratory neurons in the cat: evidence for involvement in certain types of ventilatory disturbances

Mu-opioid receptor agonists depress tidal volume, decrease chest wall compliance, and increase upper airway resistance. In this study, potential neuronal sites and mechanisms responsible for the disturbances were investigated, dose-response relationships were established, and it was determined whether general anesthesia plays a role. Effects of micro-opioid agonists on membrane properties and discharges of respiratory bulbospinal, vagal, and propriobulbar neurons and phrenic nerve activity were measured in pentobarbital-anesthetized and unanesthetized decerebrate cats. In all types of respiratory neurons tested, threshold intravenous doses of the micro-opioid agonist fentanyl slowed discharge frequency and prolonged duration without altering peak discharge intensity. Larger doses postsynaptically depressed discharges of inspiratory bulbospinal and inspiratory propriobulbar neurons that might account for depression of tidal volume. Iontophoresis of the micro-opioid agonist DAMGO also depressed the intensity of inspiratory bulbospinal neuron discharges. Fentanyl given intravenously prolonged discharges leading to tonic firing of bulbospinal expiratory neurons in association with reduced hyperpolarizing synaptic drive potentials, perhaps explaining decreased inspiratory phase chest wall compliance. Lowest effective doses of fentanyl had similar effects on vagal postinspiratory (laryngeal adductor) motoneurons, whereas in vagal laryngeal abductor and pharyngeal constrictor motoneurons, depression of depolarizing synaptic drive potentials led to sparse, very-low-frequency discharges. Such effects on three types of vagal motoneurons might explain tonic vocal fold closure and pharyngeal obstruction of airflow. Measurements of membrane potential and input resistance suggest the effects on bulbospinal Aug-E neurons and vagal motoneurons are mediated presynaptically. Opioid effects on the respiratory neurons were similar in anesthetized and decerebrate preparations.     

刺激黄雀新纹状体前部大细胞核外侧部对发声和呼吸的影响

实验材料为乌拉坦麻醉的鸣禽黄雀（Ｃａｒｄｕｅｌｉｓ ｓｐｉｎｕｓ）。观察了电及化学刺激新纹状体前部大细胞核外侧部（１ＭＡＮ）对发声和呼吸的影响。结果如下：（１）电刺激１ＭＡＮ的不同区域都引起鸣叫反应。（２）长串电脉冲刺激１ＭＡＮ使呼吸频率增加,呼吸幅度降低。（３）短串电脉冲刺激１ＭＡＮ,落位于吸气相,产生吸气要断效应;落位于呼气相,可使呼气时程延长,以冲刺激１ＭＡＮ,落位于吸气相,产生吸气切断效应     

Effect of head-down tilt on respiratory responses and human inspiratory muscle activity

The effect of a head-down tilt on the responses of the external respiration system and the functional capacity of the diaphragm and parasternal muscles were investigated in 11 healthy subjects. A 30-min head-down tilt posture (−30° relative to the horizontal) significantly increased the inspiratory time, decreased the respiration rate and the inspiratory and expiratory flow rates; and increased the airway resistance compared to these values in the vertical posture. There were no significant changes in tidal volume or minute ventilation. The electromyograms (EMGs) of the diaphragm and parasternal muscles showed that the constant values of tidal volume and minute ventilation during head-down tilt could be provided by an increase in the electric activity of the thoracic inspiratory muscles. It was established that the contribution of the thoracic inspiratory muscles increased, while the diaphragms’ contribution decreased, during patient, spontaneous breathing. The maximal inspiratory effort (Muller’s maneuver) during a head-down tilt evoked the opposite EMG-activity pattern: the contribution of inspiratory thoracic muscles was decreased and the diaphragm EMG activity was increased compared to the vertical posture. These results suggest that coordinated modulations in inspiratory muscle activity make it possible to preserve the functional reserve of human inspiratory muscles during a short-term head-down tilt.     

兔边缘系统隔区呼吸相关神经元

本实验在42只家兔给与 Urethane 半量麻醉,在边缘系统隔区用玻璃微电极方法记录了60个自发的呼吸相关神经元单位放电:吸气型30个单位;呼气型16个单位;跨时相型14个单位。断双侧迷走神经,静脉注入尼克刹米后,呼吸相关神经元单位放电与呼吸节律变化具有伴随性,呈正相关。窒息可以诱发隔区神经元呼吸节律放电。延髓第四脑室局部注入2%Sod。pentothal 后,随呼吸节律抑制、隔区呼吸相关神经元单位放电立即消失。上述结果提示:到达边缘系统隔区的呼吸信息在自主功能及情绪活动的协调方面,可能被认为是有意义的。     

Effects of hypoxia on the respiratory activity generated by semi-isolated medullo-spinal preparations of early postnatal rats

The effects of short- and long-lasting (2-min-long and up to 30-min-long) hypoxia episodes on the inspiratory activity (IA) recorded from then. phrenicus were tested in experiments on superfusedin situ semi-isolated medullo-spinal preparations (SIMSP) of newborn (the lst day of life) and 4- to 5-day-old rats. Hypoxia was provided by superfusion of the preparations with low-O₂ solution. Short-lasting hypoxia evoked no significant modulation of the IA in preparations of newborn animals, while two-phase responses (an initial, up to 30 sec, increase in the frequency of inspiratory discharges, followed by their longer, up to 4 min, suppression) were observed in 4- to 5-day-old preparations. Long-lasting hypoxia suppressed activity in then. phrenicus of 1-day-old preparations, and this effect was replaced in five cases by the development of sporadic low-amplitude and short-lasting inspiratory discharges. These shortened discharges were qualified as gasps. The responses of 4- to 5-day-old SIMSP to long-lasting hypoxia episodes were more complex. An initial increase in the IA frequency lasted up to 30 sec, and in 4–6 min it was followed by complete suppression of the activity. In some of the SIMSP, permanent tonic activity appeared in then. phrenicus within the period of total absence of inspiratory discharges, which could be followed by generation of short low-amplitude gasping discharges. Against the background of gasping pattern, eupnoe-like discharges appeared in four preparations. Under control conditions, transerve section of the ventrolateral medullary regions (VLMR) at a middle level of then. hypoglossus root abolished respiratory activity in all studied SIMSP. Yet, in some of the SIMSP of both newborn and 4- to 5-day-old animals long-lasting hypoxia testing evoked weak tonic activity in then. phrenicus followed by the appearance of gasping discharges. After the transection of the VLMR at the caudal edge of then. hypoglossus root, long-lasting hypoxia evoked only weak tonic responses in some SIMSP of both age groups, and there were no phasic discharges in this case. The results of our experiments, first, show that the respiratory activity in newborn animals is more resistant to hypoxia than that in 4-to 5-day-old rats, and, second, they allow us to suppose that the gasp-generating medullary structures are localized in more caudal medullary regions. We discuss the questions of how the eupnoe-generating and gasp-generating medullary structures are formed in rats during their initial four to five postnatal days, and what specific features are typical of hypoxia-related respiratory responses in these animals.Neirofiziologiya/Neurophysiology, Vol. 28, No. 2/3, pp. 121–131, March–June, 1996.     

正常猫膈神经单纤维电活动特征

在麻醉猫和麻痹的切断迷走神经的清醒猫,观察了膈神经单纤维电活动特征。1.电活动类型:按膈神经单纤维放电与其总干放电的相位关系分为三种类型。(1)完全同步型,即单纤维放电与总干放电同时开始并同时停止,占76.9％。(2)部分同步型占15.4％,其中早期同步,即单纤维放电与总干放电同时开始,但提前终止,占1.9％,中期同步,即单纤维放电较总干放电开始晚,又提前终止,占5.8％,晚期同步,即单纤维放电较总干放电开始晚,但两者同时终止,占7.7％。(8)非同步型,即吸气相和呼气相都有放电,但呼气相时冲动频率较低,占7.7％。前两型为单纯的吸气性放电,共占92.3％。2.单纤维放电平均参数值:麻醉猫每次吸气发放11个冲动,其频率为21次/秒,清醒猫每次吸气发放18个冲动,其频率为34次/秒。结果表明:猫膈神经单纤维放电类型和文献上报导的直接记录膈神经运动神经元放电一致,即以单纯的吸气性放电为最多。     

Development of activity in intercostal-muscle motor nuclei in the thoracic section (intact and deafferentated) of the spinal cord

During a respiratory period there is regular recruitment of units with different characteristics of impulse discharge in the motor nuclei of the intercostal muscles. The unit discharges terminate randomly. After bilateral deafferentation of the thoracic section the frequency of impulses of intercostal motor units (MU), the regularity of their recruitment, and the sequence of activity of expiratory and inspiratory motor nuclei were nearly normal. Hence it is concluded that segmental afferentation is not necessary for coordinated activity of the two nuclei in normal respiration.Institute of Problems of Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 3, No. 2, pp. 194–199, March–April, 1971.     

面神经核腹内侧区微量注射三种递质的呼吸效应

实验用兔,在乌拉坦静脉麻醉、切断双侧颈迷走神经、自主呼吸条件下进行,以膈神经放电作呼吸指标。观察了面神经核腹内侧区(VMNF)微量注射三种递质对呼吸节律的影响。结果如下:(1)VMNF 区微量注射肾上腺素呼吸频率增加,膈神经吸气性放电的递增速度加快,积分幅度升高,VMNF 区微量注射妥拉苏林,呼吸频率下降且妥拉苏林可阻断肾上腺素的呼吸效应。(2)VMNF 区微量注射γ-氨基丁酸、甘氨酸导致呼吸频率下降,吸气时程、呼气时程延长。提示肾上腺素、γ-氨基丁酸、甘氨酸可能作为递质作用于 VMNF 区的神经元而发挥呼吸调节作用。     

家兔单侧、双侧B(o)tzinger复合体内微量注射甘氨酸及士的宁对膈神经放电的影响

实验在３４只氨基甲酸乙酯麻醉,断双侧瞳神经,肌松,人工通气的家兔上进行。单侧和双侧Ｂｏｔｚｉｎｇｅｒ复合体内微量注射抑制性神经递质甘氨酸及其受体阻断剂 宁,观察膈神经放电的变化。     

Factors affecting central inspiratory modulation of hypoglossal motoneuron activity in newborn pigs

In newborn pigs (4-6 days old), recordings of efferent whole hypoglossal and phrenic nerve discharges were obtained during hyperoxia (or normoxia) and during hypoxia, before and after bilateral vagotomy. With intact vagi, spontaneous hypoglossal inspiratory activity was not observed and was not elicited by either spontaneous changes of electroencephalogram (EEG) or hypoxic stimulation (15% O2 in N2). After bilateral vagotomy, some animals had episodes of spontaneous hypoglossal inspiratory activity; power spectral analysis of EEG demonstrated that this inspiratory activity appeared synchronously with shifts of major peaks in EEG spectra from the delta band (0.5-3.5 Hz) to the theta band (3.5-7.0 Hz). Hypoglossal inspiratory discharges were also elicited by hypoxic stimulation and usually had a decrementing discharge pattern; in some cases, this activity had an augmenting discharge pattern. Our results suggest that hypoglossal motoneurons are poorly modulated by central inspiratory drive, requiring additional facilitatory influences, i.e. corticobulbar, intra-bulbar, chemical drive, before such modulation is observed.     

Parameters of discharges of respiratory neurons of the ventrolateral medullary regions in early postnatal rats

In experiments on superfusedin situ semi-isolated medullo-spinal preparations (SIMSP) of newborn (1st day of life) and 4- to 5-day-old rats, we studied the parameters of extracellularly recorded spike activity of respiratory neurons of the ventrolateral medullary regions (VLMR). In SIMSP of 4- to 5-day-old rats, the frequency of discharges of pre-inspiratory, inspiratory, and expiratory neurons is shown to be significantly higher, while the dispersion of its values is considerably lower, as compared with the corresponding values for newborn animals. In the majority of pre-inspiratory and inspiratory neurons of SIMSP of newborn rats, irregular low-frequency discharges are usually generated within the interinspiration phase. The relative intensity of suppression of discharges of pre-inspiratory and expiratory neurons within an inspiration phase is much lower in SIMSP of newborn rats, as compared with that in 4- to 5-day-old preparations. The activity of most pre-inspiratory neurons manifests a trend toward transformation from a two-phase pattern in newborn rats (with two frequency peaks, pre- and post-inspiratory) to a monophasic pattern (with one pre-inspiratory frequency peak) typical of 4- to 5-day-old animals. The effects of electrical stimulation of the site of localization of pre-inspiratory neurons showed that in SIMSP of both age groups of rats an inspiratory response could be evoked in then. phrenicus only in the case when stimulation was applied within the second half of an interinspiratory phase. Therefore, it can be supposed that the respiratory network in newborn animals is to a considerable extent immature in the morphofunctional aspect. It seems probable that in early postnatal rats pre-inspiratory neurons are involved in the medullary mechanisms foron-off switching of the inspiratory and expiratory phases.Neirofiziologiya/Neurophysiology, Vol. 28, No. 4/5, pp. 207–217, July–October, 1996.     

Effect of lung inflation on the respiratory frequency and heart rate of premature neonates

Changes in the respiratory frequency and heart rate in response to 10 seconds' inflation of the lungs with oxygen by the CPAP method were studied in 32 premature neonates. Elevation of the pressure in the airways and lungs of 0.25, 0.49, 0.73 and 0.98 kPa led to a slower respiration rate or to apnoea. The incidence of apnoea rose in proportion to the pressure. When inflation was started, forced inspiratory efforts (a gasp reflex) occurred. The incidence of the efforts was higher at higher inflation pressures, but their intensity was not correlated to the size of the pressure. They were manifested in a drop in oesophageal pressure to a mean -2.0 +/- 0.2 kPa and their mean duration was 169 +/- 8 ms. The administration of oxygen without an increase in pressure produced neither apnoea nor forced inspiratory reactions. Neither an increase in the pressure in the airways and lungs to the above values, nor the plain administration of oxygen, produced any significant changes in the instantaneous heart rate.     

Regional left ventricular performance during normal and obstructed spontaneous respiration

To clarify the effects of respiration on left ventricular (LV) dimensions and shortening, we studied chronically instrumented dogs with endocardial sonomicrometer crystals in the anterior-posterior (AP), septal to lateral (SL), and long axes (LA) following pericardiectomy. Ten anesthetized dogs were examined during spontaneous unobstructed respiration, partial inspiratory obstruction (PIO), and Mueller maneuvers (MM). During unobstructed inspiration, end-diastolic dimensions (EDD) demonstrated a significant increase in the AP and a similar decrease in the SL axis (i.e., noncongruent shape changes). During PIO only the SL EDD diminished significantly, while no significant changes occurred in any EDD during MM. Individual dogs also demonstrated noncongruent shape changes at end systole during inspiration. However, the end-systolic dimensions for the entire group demonstrated a significant increase in one dimension during each inspiratory mode with no significant changes in the other two axes suggesting an increased ventricular volume. Regional shortening declined only in the SL axis during both unobstructed respiration and PIO. Spontaneous sighs with large tidal volumes, yet smaller changes in pleural pressure than during the MM, were associated with marked noncongruent shape changes in both diastole and systole. We conclude that 1) estimates of LV volumes during respiration based on only one or two axes and assuming regional congruent shape changes may be misleading; and 2) lung volume changes can affect LV geometry independently of changes in pleural pressure.     

Spectral characteristics of electrical activity of the respiratory center in brain processes in fetus and newborn rats in vitro

Power spectral analysis of inspiratory discharges of C3-C5 ventral roots in brainstem-spinal cord preparation from foetal (18 and 20 gestation days) and newborn (0-1 and 2-3 postnatal days) rats was performed. The respiratory centre perinatal development manifests itself by decreasing of respiratory rhythm variability and increasing of inspiratory burst duration. In foetal inspiratory bursts, low-frequency oscillations (1-10 Hz) dominate. In early postnatal stage, the relative power of low-frequency oscillations begin to decrease, and medium frequency oscillations (10-50 Hz) start to dominate over the inspiratory discharge. The data obtained suggests, that perinatal maturation of respiratory centre is characterised by stabilisation of the respiratory rhythm generation and developmental alteration of inspiratory activity's spectral and temporary parameters.     

Existence of respiratory interneurons in the cervical spinal cord of the rabbit

A spinal "respiration" generator has been shown to fire phrenic motoneurones in rhythmic bursts. It is very likely driven through bulbo-spinal inspiratory neurones in intact preparations. Although no direct evidence for respiratory interneurones at the C4-C5 spinal levels has been obtained so far (except for Renshaw cells ), it is currently believed that only few inspiratory inputs to the phrenic motoneurones are transmitted monosynaptically from the medulla. We have tried here to record spinal interneuronal respiratory activities in decorticate, unanaesthetized, vagotomized and curarized rabbit preparations. Different functional categories of interneurones could be identified at the C4-C5 spinal levels: inspiratory and expiratory interneurons with various discharge patterns which rather well correspond to the functional categories of inspiratory and expiratory bulbo-spinal neurones described by Bianchi and Richter. In addition, multiunit inspiratory bursting could be followed over several 100 microns during each electrode penetration. The different categories of interneurones were encountered laterally from 700 to 1,000 microns, at depths ranging from 300 to 500 microns dorsally to the phrenic nucleus, down to the nucleus itself. These results indicate that part of the medullary inspiratory drive is channelled via spinal cord interneurones; they also suggest that an inhibition of phrenic motoneurones from the bulbo-spinal expiratory drive takes place via interneurones.     

兔孤束核腹外侧区微量注射谷氨酸钠及甘氨酸对膈神经放电的影响

实验在４０只麻醉、制动、断双侧颈迷走神经和人工通气的家兔上进行。在孤束核腹外侧区微量注射神经元胞体兴奋剂谷氨酸钠和抑制剂甘氨酸,探讨膈神经放电的变化。结果：微量注射谷氨酸钠,可使膈神经放电脉冲数明显增加,吸气时程延长,呼气时程缩短,呼吸频率变化不明显;微量注射甘氨酸,则膈神经放电脉冲数显著减少,甚至停止,吸气时程缩短,呼气时程不规则延长,呼吸频率降低。上述结果提示：孤束核腹外侧区对呼吸节律的形成具