Effect of pyracetam on fatigue of inspiratory muscles in cats

The aim of the work was to study the influence of pyracetam on respiratory muscles fatigue and ventilatory disorders caused by inspiratory resistive load in cats. The experiments have show that after the use of pyracetam in conditions of fatigue total bioelectric activities of inspiratory muscles and of the phrenic nerve and transdiaphragmal pressure restore; duty cycle, respiratory rate and tidal volume per minute decrease. The conclusion is drawn that pyracetam in the dose 300 mg/kg, in intravenous administration, compensates inspiratory muscle fatigue at the expense of its central mechanism of action.     

Respiratory muscle control during vomiting

The changes in thoracic and abdominal pressure that generate vomiting are produced by coordinated action of the major respiratory muscles. During vomiting, the diaphragm and external intercostal (inspiratory) muscles co-contract with abdominal (expiratory) muscles in a series of bursts of activity that culminates in expulsion. Internal intercostal (expiratory) muscles contract out of phase with these muscles during retching and are inactive during expulsion. The periesophageal portion of the diaphragm relaxes during expulsion, presumably facilitating rostral movement of gastric contents. Recent studies have begun to examine to what extent medullary respiratory neurons are involved in the control of these muscles during vomiting. Bulbospinal expiratory neurons in the ventral respiratory group caudal to the obex discharge at the appropriate time during (fictive) vomiting to activate either abdominal or internal intercostal motoneurons. The pathways that drive phrenic and external intercostal motoneurons during vomiting have yet to be identified. Most bulbospinal inspiratory neurons in the dorsal and ventral respiratory groups do not have the appropriate response pattern to initiate activation of these motoneurons during (fictive) vomiting. Relaxation of the periesophageal diaphragm during vomiting could be brought about, at least in part, by reduced firing of bulbospinal inspiratory neurons.     

Phrenic and external intercostal motoneuron activity during progressive asphyxia

Phrenic and external intercostal motoneuron activities were compared during progressive asphyxia induced by the interruption of artificial ventilation in the pentobarbital-urethan-anesthetized, gallamine-paralysed rabbit. The relative augmentation of inspiratory activity of the T1-T4 external intercostal nerves was significantly greater than that of the phrenic nerve during asphyxic hyperpnea. This was associated with a greater recruitment of intercostal than of phrenic motoneurons, particularly late in the hyperpneic phase immediately before the period of asphyxic apnea. However, peak and average discharge frequencies developed by intercostal motoneurons (n = 20) were only approximately 60% of those of the phrenic motoneurons (n = 28). Gasping respiration terminated the apneic period and was associated with a further intense recruitment of intercostal though not of phrenic motoneurons, but discharge frequencies developed by the intercostal motoneurons remained approximately 60% of those of the phrenic motoneurons. The instantaneous frequency profiles generated by the motoneurons often exhibited progressive changes during the terminal stages of hyperpnea (reduction in inspiratory duration and duty cycle and increases in inspiratory slope and discharge frequencies) such that much of the character of gasping respiration became evident before the apnea. Such smooth transitional sequences do not obviate the existence of an "independent gasping center" but do require that such a proposed center at least possess the capacity for interaction with those sites responsible for the generation of eupneic and hyperpneic respiration.     

家兔脊髓蛛网膜下腔注射乙酰胆碱对膈神经放电的影响

实验在50例麻醉、麻痹和切断双侧迷走神经的家兔上进行。用双极银丝电极引导膈神经放电,经放大、幅度积分而后记录在 X-Y 记录仪上。脊髓蛛网膜下腔注射乙酰胆碱(ACh)50μg 后,膈神经吸气放电幅度增加,平均增加30.6±11.6%.ACh 的这一效应可被阿托品阻断,但不能被六甲双铵、酚妥拉明和心得安阻断。但单独注射上述任何一种受体阻断剂均不能改变膈神经的放电活动。上述结果提示,脊髓蛛网膜下腔注射 ACh 可兴奋膈运动神经元,而且 ACh 的这一兴奋效应是由 Μ 受体中介的,但在正常生理情况下,胆碱能递质系统对膈神经元似无紧张性兴奋作用。因此,ACh 递质可能在脊髓水平对高级中枢下传的呼吸驱动信息的整合中起兴奋性调制作用。     

Neural drive to tongue protrudor and retractor muscles following pulmonary C-fiber activation.

Hypoglossal (XII) nerve recordings indicate that pulmonary C-fiber (PCF) receptor activation reduces inspiratory bursting and triggers tonic discharge. We tested three hypotheses related to this observation: 1) PCF receptor activation inhibits inspiratory activity in XII branches innervating both tongue protrudor muscles (medial branch; XIImed) and retractor muscles (lateral branch; XIIlat); 2) reduced XII neurogram amplitude reflects decreased XII motoneuron discharge rate; and 3) tonic XII activity reflects recruitment of previously silent motoneurons. Phrenic, XIImed, and XIIlat neurograms were recorded in anesthetized, paralyzed, and ventilated rats. Capsaicin delivered to the jugular vein reduced phrenic bursting at doses of 0.625 and 1.25 mug/kg but augmented bursting at 5 mug/kg. All doses reduced inspiratory amplitude in XIImed and XIIlat (P < 0.05), and these effects were eliminated following bilateral vagotomy. Single-fiber recordings indicated that capsaicin causes individual XII motoneurons to either decrease discharge rate (n = 101/153) or become silent (n = 39/153). Capsaicin also altered temporal characteristics such that both XIImed and XIIlat inspiratory burst onset occurred after the phrenic burst (P < 0.05). Increases in tonic discharge after capsaicin were greater in XIImed vs. XIIlat (P < 0.05); single-fiber recordings indicated that tonic discharge reflected recruitment of previously silent motoneurons. We conclude that PCF receptor activation reduces inspiratory XII motoneuron discharge and transiently attenuates neural drive to both tongue protrudor and retractor muscles. However, tonic discharge appears to be selectively enhanced in tongue protrudor muscles. Accordingly, reductions in upper airway stiffness associated with reduced XII burst amplitude may be offset by enhanced tonic activity in tongue protrudor muscles.     

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。     

Inspiratory rhythm in airway smooth muscle tone

In anesthetized paralyzed open-chested cats ventilated with low tidal volumes at high frequency, we recorded phrenic nerve activity, transpulmonary pressure (TPP), and either the tension in an upper tracheal segment or the impulse activity in a pulmonary branch of the vagus nerve. The TPP and upper tracheal segment tension fluctuated with respiration, with peak pressure and tension paralleling phrenic nerve activity. Increased end-tidal CO2 or stimulation of the carotid chemoreceptors with sodium cyanide increased both TPP and tracheal segment tension during the increased activity of the phrenic nerve. Lowering end-tidal CO2 or hyperinflating the lungs to achieve neural apnea (lack of phrenic activity) caused a decrease in TPP and tracheal segment tension and abolished the inspiratory fluctuations. During neural apnea produced by lowering end-tidal CO2, lung inflation caused no further decrease in tracheal segment tension and TPP. Likewise, stimulation of the cervical sympathetics, which caused a reduction in TPP and tracheal segment tension during normal breathing, caused no further reduction in these parameters when the stimulation occurred during neural apnea. During neural apnea the tracheal segment tension and TPP were the same as those following the transection of the vagi or the administration of atropine (0.5 mg/kg). Numerous fibers in the pulmonary branch of the vagus nerve fired in synchrony with the phrenic nerve. Only these fibers had activity which paralleled changes in TPP and tracheal tension. We propose that the major excitatory input to airway smooth muscle arises from cholinergic nerves that fire during inspiration, which have preganglionic cell bodies in the ventral respiratory group in the region of the nucleus ambiguus and are driven by the same pattern generators that drive the phrenic and inspiratory intercostal motoneurons.     

Optimization of function of breath by means of training with additional resistive resistance

Research on studying influence of the rate of muscular training in conditions of additional resistive resistance to breath on a level of physical working capacity, aerobic productivity and a functional condition of system of breath was performed. It is shown, that regular muscular loadings in a combination to resistive resistance to breath in a mode of an interval exposition provide an increase of profitability and efficiency of functioning of breathing system as expressed in increase of expiratory force respiratory muscles, rationalization of parity of volumetric-time parameters of breath pattern that promotes more effective gas exchange and decrease in power cost of respiratory movements and as a result leads to increase in aerobic productivity and growth of the general and special working capacity. At continuous exposition of resistive resistance against a background of muscular training, the increase of inspiratory force of respiratory muscles, increase of functional capacity of system of breath were revealed at physical activity as well as a significant gain of the general physical working capacity.     

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.     

High-frequency oscillations within early and late phases of the phrenic neurogram

Spectral analyses were performed on phrenic neurogram recordings from 18 cats to identify high-frequency oscillations (HFOs) inherent in the signals at different phases of inspiratory activity. Gating the analysis for the entire inspiratory phase resulted in dual spectral HFOs (27 and 83 Hz), both of which persisted when the analysis was repeated on the later phase of phrenic inspiratory activity alone (29 and 82 Hz). A third pass at the same data, gating for just the early phase of phrenic discharge, however, resulted in single spectral HFOs at the higher frequency only (86 Hz). Because both early and late recruited phrenic motoneurons carry both higher and lower spectral frequencies, these results demonstrate that the lower frequency HFO is distinctly delayed in onset compared with the higher frequency HFO, the latter of which is believed to have a brain stem origin. This delayed onset may be important in identifying the source of the lower frequency HFO, which appears to be specific to various respiratory efferent systems.     

Respiratory responses in reversible diaphragm paralysis

The effects of diaphragm paralysis on respiratory activity were assessed in 13 anesthetized, spontaneously breathing dogs studied in the supine position. Transient diaphragmatic paralysis was induced by bilateral phrenic nerve cooling. Respiratory activity was assessed from measurements of ventilation and from the moving time averages of electrical activity recorded from the intercostal muscles and the central end of the fifth cervical root of the phrenic nerve. The degree of diaphragm paralysis was evaluated from changes in transdiaphragmatic pressure and reflected in rib cage and abdominal displacements. Animals were studied both before and after vagotomy breathing O2, 3.5% CO2 in O2, or 7% CO2 in O2. In dogs with intact vagi, both peak and rate of rise of phrenic and inspiratory intercostal electrical activity increased progressively as transdiaphragmatic pressure fell. Tidal volume decreased and breathing frequency increased as a result of a shortening in expiratory time. Inspiratory time and ventilation were unchanged by diaphragm paralysis. These findings were the same whether O2 or CO2 in O2 was breathed. After vagotomy, no significant change in phrenic or inspiratory intercostal activity occurred with diaphragm paralysis in spite of increased arterial CO2 partial pressure. Ventilation and tidal volume decreased significantly, and respiratory timing was unchanged. These results suggest that mechanisms mediated by the vagus nerves account for the compensatory increase in respiratory electrical activity during transient diaphragm paralysis. That inspiratory time is unchanged by diaphragm paralysis whereas the rate or rise of phrenic nerve activity increases suggest that reflexes other than the Hering-Breuer reflex contribute to the increased respiratory response.     

蓝斑核对上呼吸道阻力肌—颏舌肌功能的影响

本实验在３８只经氨基甲酸乙酯麻醉的健康家兔上进行,观察了电、化学刺激蓝斑核（ＬＣ）对颏舌肌功能的影响。结果如下：（１）长串电脉冲刺激蓝斑核使颏舌肌肌电活动明显增强,表现为长吸性肌电积分幅度升高,膈肌亦出现与颏舌肌同步的肌电活动增强。（２）ＬＣ内微量注射胞体兴奋剂谷氨酸钠,也引起明显的颏舌肌和膈肌肌电活动增强。（３）上述电、化学刺激的区域对照和盐水对照实验,均未出现有意义的肌电改变。提示：电、化学刺激ＬＣ可特异性增强上呼吸道阻力肌──颏舌肌的紧张性活动,具有减小上呼吸道阻力的作用,这对于某些上呼吸道阻塞性疾病发病机制的研究可能具有重要的意义。     

Respiratory response to partial paralysis in anesthetized dogs

The ability to maintain alveolar ventilation is compromised by respiratory muscle weakness. To examine the independent role of reflexly mediated neural mechanisms to decreases in the strength of contraction of respiratory muscles, we studied the effects of partial paralysis on the level and pattern of phrenic motor activity in 22 anesthetized spontaneously breathing dogs. Graded weakness induced with succinylcholine decreased tidal volume and prolonged both inspiratory and expiratory time causing hypoventilation and hypercapnia. Phrenic peak activity as well as the rate of rise of the integrated phrenic neurogram increased. However, when studied under isocapnic conditions, increases in the severity of paralysis, as assessed from the ratio of peak diaphragm electromyogram to peak phrenic activity, produced progressive increases in inspiratory time and phrenic peak activity but did not affect its rate of rise. After vagotomy, partial paralysis induced in 11 dogs with succinylcholine also prolonged the inspiratory burst of phrenic activity, indicating that vagal reflexes were not solely responsible for the alterations in respiratory timing. Muscle paresis was also induced with gallamine or dantrolene, causing similar responses of phrenic activity and respiratory timing. Thus, at constant levels of arterial CO2 in anesthetized dogs, respiratory muscle partial paralysis results in a decrease in breathing rate without changing the rate of rise of respiratory motor activity. This is not dependent solely on vagally mediated reflexes and occurs regardless of the pharmacological agent used. These observations in the anesthetized state are qualitatively different from the response to respiratory muscle paralysis or weakness observed in awake subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Some effects of superior laryngeal nerve stimulation on sympathetic preganglionic neuron firing

Repetitive electrical stimulation of afferent fibers in the superior laryngeal nerve (SLN) evoked depressant or excitatory effects on sympathetic preganglionic neurons of the cervical trunk in Nembutal-anesthetized, paralyzed, artifically ventilated cats. The depressant effect, which consisted of suppression of the inspiration-synchronous discharge of units with such firing pattern, was obtained at low strength and frequency of stimulation (e.g. 600 mV, 30 Hz) and was absent at end-tidal CO2 values below threshold for phrenic nerve activity. The excitatory effect required higher intensity and frequency of stimulation and was CO2 independent. The depressant effect on sympathetic preganglionic neurons with inspiratory firing pattern seemed a replica of the inspiration-inhibitory effect observed on phrenic motoneurons. Hence, it could be attributed to the known inhibition by the SLN of central inspiratory activity, if it is assumed that this is a common driver for phrenic motoneurons and some sympathetic preganglionic neurons. The excitatory effect, on the other hand, appears to be due to connections of SLN afferents with sympathetic preganglionic neurons, independent of the respiratory center.     

Effects of PGF2 alpha on the EMG of costal and crural parts of the diaphragm of the newborn pig

We investigated the effects of PGF2 alpha on the breathing patterns and electric activity of costal and crural parts of the diaphragm in 9 anesthetized newborn pigs. The change in diaphragmatic tension was evaluated as the change in transdiaphragmatic pressure. Because PGF2 alpha induces bronchoconstriction and an increase in respiratory resistances, the changes induced by prostaglandin were evaluated as differences between bronchoconstriction after PGF2 alpha and resistive load obtained by applying gradual occlusion to the inspiratory line of the breathing circuit. Our results show that PGF2 alpha decreased respiratory frequency with lengthening of expiratory time, while the resistive load increased both respiratory phases. The changes in breathing pattern were associated with different electrical activities of the diaphragm. While resistive load did not significantly change the EMG power spectrum, PGF2 alpha recruited new motor units. Furthermore, resistive load induced synchronization of the inspiratory time discharge of the costal and crural parts of the diaphragm, while after PGF2 alpha infusion there was an early inspiratory discharge of the crural part.     

Relationship between respiratory nerve and muscle activity and muscle force output.

To demonstrate the most satisfactory way of using electrical activities of respiratory nerves and muscles, activities of phrenic nerve and external intercostal muscle (ICM) and the airway pressure changes generated by respiratory muscle contraction were recorded in anesthetized cats during complete airway occlusion. Electrical activities were rectified, integrated and processed in terms of peak and average inspiratory rates per 0.1 s and of total activity per breath. Peak rate of phrenic nerve activity exhibited a high linear correlation (r = 0.974) with peak inspiratory pressure. Average phrenic rate showed a similar high correlation (r = 0.973). Peak rate of external ICM was linearly related to peak pressure but the correlation was less good (r = 0.915). Total phrenic activity per breath was too dependent upon inspiratory duration to be a satisfactory correlate (r = 0.674). In this experiment occlusion pressure was an index of muscle force generation and respiratory control system output. It is concluded that peak or average rates of phrenic activity provide an electrical index of output changes. On theoretical grounds, peak rate is probably better.     

Expiratory muscle fatigue in normal subjects

We examined expiratory muscle fatigue during expiratory resistive loading in 11 normal subjects. Subjects breathed against expiratory resistances at their own breathing frequency and tidal volume until exhaustion or for 60 min. Respiratory muscle strength was assessed from both the maximum static expiratory and inspiratory mouth pressures (PEmax and PImax). At the lowest resistance, PEmax and PImax measured after completion of the expiratory loaded breathing were not different from control values. With higher resistance, both PEmax and PImax were decreased (P less than 0.05), and the decrease lasted for greater than or equal to 60 min. The electromyogram high-to-low frequency power ratio for the rectus abdominis muscle decreased progressively during loading (P less than 0.01), but the integrated EMG activity did not change during recovery. Transdiaphragmatic pressure during loading was increased 3.6-fold compared with control (P less than 0.05). These findings suggest that expiratory resistive loaded breathing induces muscle fatigue in both expiratory and inspiratory muscles. Fatigue of the expiratory muscles can be attributed directly to the high work load and that of the inspiratory muscles may be related to increased work due to shortened inspiratory time.     

Intrinsic properties of pharyngeal and diaphragmatic respiratory motoneurons and muscles.

Breathing is a complex act requiring the coordinated activity of multiple groups of muscles. Thoracic and abdominal respiratory muscles expand and contract the lungs, whereas pharyngeal and laryngeal respiratory muscles maintain upper airway patency and regulate upper airway resistance. An appreciation of the importance of the latter muscle group in maintaining ventilatory homeostasis and in the pathophysiology of sleep apnea has led to extensive studies examining the neural regulation of pharyngeal dilator muscles. The present review examines the role of heterogeneity in motoneuron and muscle properties in determining the diversity in the electrical and mechanical behaviors of thoracic compared with pharyngeal muscle groups. Specifically, phrenic and hypoglossal motoneuron electrophysiological properties influence whether and the extent to which these neurons will fire in response to a given synaptic input arising from chemo- and mechanoreceptors and from respiratory and nonrespiratory pattern generators. Furthermore, thoracic and pharyngeal muscle properties determine the mechanical response to motoneuronal activity, including the speed of contraction, relationships between motoneuron firing frequency and force production, and whether force is maintained during repetitive activation. Heterogeneity in the functional capabilities of these motoneurons and muscles is in turn determined by diversity of their structural and biochemical properties. Thus, intrinsic properties of respiratory motoneurons and muscles act in concert with neuronal drives in defining the complex electrical and mechanical behavior of pharyngeal and thoracic respiratory motor systems.     

Respiratory function of pharyngeal muscles

This article reviews experimental studies of pharyngeal muscles with emphasis on m. genioglossus as a major muscle dilating pharynx and discusses neuromuscular mechanisms that maintains patency of upper airway. Mechanisms of inspiratory activation of genioglossus muscle in comparative with diaphragm are also discussed. Experimental data suggesting that upper airway muscles have a significant role in compensation of added inspiratory load are presented. It allows to regard pharyngeal dilating muscles as accessory muscles of respiration. Activation of m. genioglossus (together with others muscles dilating the pharynx) decreases airway resistance and thereby facilitates the load compensation function of "pumping" muscles. Similar to diaphragm involvement of the pharynx dilating muscles in the load compensatory response is resulted from a complex integration of several influences originating from mechano- and chemoreceptors.     

Airway resistance and respiratory muscle function in snorers during NREM sleep

The effect of non-rapid-eye-movement (NREM) sleep on total pulmonary resistance (RL) and respiratory muscle function was determined in four snorers and four nonsnorers. RL at peak flow increased progressively from wakefulness through the stages of NREM sleep in all snorers (3.7 +/- 0.4 vs. 13.0 +/- 4.0 cmH2O X 0.1(-1) X s) and nonsnorers (4.8 +/- 0.4 vs. 7.5 +/- 1.1 cmH2O X 1(-1) X s). Snorers developed inspiratory flow limitation and progressive increase in RL within a breath. The increased RL placed an increased resistive load on the inspiratory muscles, increasing the pressure-time product for the diaphragm between wakefulness and NREM sleep. Tidal volume and minute ventilation decreased in all subjects. The three snorers who showed the greatest increase in within-breath RL demonstrated an increase in the contribution of the lateral rib cage to tidal volume, a contraction of the abdominal muscles during a substantial part of expiration, and an abrupt relaxation of abdominal muscles at the onset of inspiration. We concluded that the magnitude of increase in RL leads to dynamic compression of the upper airway during inspiration, marked distortion of the rib cage, recruitment of the intercostal muscles, and an increased contribution of expiratory muscles to inspiration. This increased RL acts as an internal resistive load that probably contributes to hypoventilation and CO2 retention in NREM sleep.