[The Role of Insular Cortex in Autonomic Control].

The purpose of this article is to review experimental data proving that the insular cortex is involved in the regulation of visceral systems: respiratory, cardiovascular and gastrointestinal systems. The paper deals with the data on the structure of the insular cortex, the pathways in brain by which visceral information ascend to the insular cortex, the results of neurophysiological experiments and clinical observations. The experimental evidence of viscerotopical organization of not only sensor, but also motor representation of visceral systems in the insular cortex is discussed. On the basis of these data the insular cortex is defined as sensorimotor visceral cortex. It is demonstrated that one of the mechanisms of influence of the insular cortex on the regulation of internal organs is the modulation of reflex reactions which take place at the bulbar level.

[PARTICIPATION OF NO-ERGIC MECHANISMS IN REALIZATION OF RESPIRATORY EFFECTS OF PRO-INFLAMMATORY CYTOKINE INTERLEUKIN-1-BETA].

The role of NO-ergic mechanisms in the realization of the respiratory effects of pro-inflammatory cytokine IL-1beta was investigated in acute experiments on anesthetized rats. To achieve this, we studied the effect of intravenous administration of IL-1beta during inhibition of NO-synthase by N-nitro-L-arginine methyl ester (L-NAME, a non-specific blocker of NO-synthase) on the parameters of breathing and the Hering-Breuer inspiratory-inhibitory reflex. It was shown that the effect of L-NAME eliminates the IL-1beta-dependent increase of the Hering-Breuer reflex, whereas effects on breathing pattern does not change: the increase in IL-1beta system-level evokes an increase in respiratory rate, tidal volume and lung ventilation. It is assumed that one of the mechanisms of enhance in the strength inspiratory-inhibitory reflex by increasing circulatory IL-1beta level is the increased glutamate-ergic transmission on pump-neurons induced by increase in nitric oxide synthesis in cerebrovascular endothelial cells. In conclusion, NO-ergic mechanisms participate in the modulation of the vagal respiratory reflexes during the development of the acute phase of systemic inflammation.

The Mechanisms of Compensatory Responses of the Respiratory System to Simulated Central Hypervolemia in Normal Subjects.

The compensatory responses of the respiratory system to simulated central hypervolemia (CHV) were investigated in 14 normal subjects. The central hypervolemia was caused by a short-time passive head-down tilt (HDT, -30°, 30 min). The results show that CHV increased the mechanical respiratory load and the airway resistance, slowed the inspiratory flow, increased the duration of the inspiratory phase, reduced the respiratory rate, but not changed the minute ventilation. CHV induced a significant rise in inspiratory swings of alveolar pressure (184%), based on the inspiratory occlusion pressure measurement. These changes indicate a compensatory increase in the inspiratory muscle contraction force. A stable level of minute ventilation during CHV was an effect of increased EMG activity of parasternal muscles more than twice (P<0.01). A contribution of the diaphragm and scalene muscles to ventilation during spontaneous breathing in HDT was reduced. An increase of genioglossus contractile activity during HDT contributed to the stabilization of airway patency. These results suggest that a coordinated modulation of inspiratory muscles activity allows preserving a constant level of minute ventilation during a short-time intrathoracic blood volume expansion. The mechanisms of respiratory load compensation seem to be mediated by afferent information from the lung and respiratory muscle receptors and from the segmentary reflexes and intrinsic properties of the muscle fibers.

[MECHANISMS OF MODULATION OF REFLEX CONTROL OF BREATHING AT ELEVATED SYSTEMIC LEVEL OF PROINFLAMMATORY CYTOKINE INTERLEUKIN-1ß].

This study explores the hypothesis about the possible involvement of the cyclooxygenase pathway in the effects of interleukin-1beta (IL-1ß) on the breathing pattern and Heuring-Breuer respiratory reflexes. Respiratory frequency (fR), tidal volume (VT) and esophageal pressure were recorded in 29 adult male Wistar rats anaesthetized with urethane. Heuring-Breuer reflexes were tested by airway occlusion at achieving functional residual capacity (inspiratory-inhibitory reflex), and at the height of inspiration (expiratory-promoting reflex). It had been shown that an elevation of IL-1ß in the systemic circulation causes an increase in VT, fR, lung ventilation and strengthens respiratory reflexes. These respiratory effects had not been shown if IL-1ß administered after intraperitoneal injection of diclofenac, which had not any significant respiratory effects by itself. Because diclofenac is a non-specific antagonist of cyclooxygenases, it had been concluded that the prostaglandins mediate respiratory effects of IL-1ß in point of fact.

Cyclooxygenase pathway in modulation of the ventilatory response to hypercapnia by interleukin-1ß in rats.

At the present time very little is known about interactions between the systemic inflammatory and ventilatory control. Our previous study has demonstrated that the elevation of the major inflammatory cytokines interleukin-1ß (IL-1ß) in the cerebrospinal fluid (CSF) may affect the control of ventilation. The aim of the current study was to compare the respiratory effects of IL-1ß before and after pretreatment with diclofenac, a nonspecific cyclooxygenase (COX) inhibitor. Using the method of rebreathing with hyperoxic gas mixture we demonstrate that the slope of the ventilatory response to carbon dioxide decreased almost twofold from 5.6±0.52 to 2.5±0.28 ml min(-1)mmHg(-1) (p<0.01) 40 min after cerebroventricular administration of IL-1ß. In contrast, the basal level of lung ventilation increased after the elevation of IL-1ß in CSF. Diclofenac pretreatment eliminated these respiratory effects of IL-1ß. The data indicate that the ability of IL-1ß to enhance basal ventilation and to reduce the ventilatory hypercapnic response is mediated by the COX pathway.

[Hardware and software for EMG recording and analysis of respiratory muscles of human].

This paper presents a new hardware and software system that allows to not only record the EMG of different groups of the respiratory muscles, but also hold its amplitude-frequency analysis, which allows to determine the change in the contribution to the work of breathing of a respiratory muscles and detect early signs of fatigue of the respiratory muscles. Presented complex can be used for functional diagnostics of breath in patients and healthy people and sportsmen.

[The effect of cerebral glutamate enhanced level on the respiratory system of anesthetized rats].

A cerebral level of glutamate is one of the determinants of the central mechanisms of respiratory control. It had been hypothesized that endogenous glutamate could have a modulating effect on the functioning of mechanisms for neural control of respiratory function. Acute experiments on spontaneuosly breathing, urethane-anesthetized rats had been performed to study the respiratory effects of cerebroventricular microinjection of glutamate. It has been shown that a higher level of cerebral glutamate increases breathing rate and electrical activity of the diaphragm, and strengthen the Hering-Breuer reflex. These effects had a clear character of the phase. The results confirm the hypothesis suggested and prove that the increase in cerebral levels of glutamate leads to the activation of glutamate receptors of various types.

Effects of stimulation of the insular cortex on execution of the antrofundal reflex in conscious dogs.

Neuroanatomical studies demonstrated the existence of direct descending projections from the insular cortex to the area of the solitary tract nucleus responsible for mediating the vagovagal reflexes of the proximal part of the gastrointestinal tract. These studies provided grounds for suggesting that one of the mechanisms mediating the influences of the insular cortex on stomach function may be modulation of its vagovagal reflex reactions, one of which is the antrofundal inhibitory reflex. Experiments on conscious dogs were performed to study the effects of electrical stimulation of the insular cortex on execution of the antrofundal gastric reflex in conditions of intermittent gastrointestinal tract activity during fasting. Stretching of the walls of the antral segment of the stomach during the active period of intermittent gastric activity led to suppression of contractions in the fundal segment. Electrical stimulation of the insular cortex was found to prolong this reflex reaction. Thus, one result of activation of the insular area of the cortex is enhancement of the inhibitory vagovagal gastric reflexes, in all probability occurring as a result of modulation of neurotransmission in the vagovagal reflex arc system.

Effects of gamma-aminobutyric acid on the Hering-Breuer inspiration-inhibiting reflex.

Acute experiments on rats were performed to study the effects of intraventricular microinjections of gamma-aminobutyric acid (GABA) on the volume-time parameters of external respiration and the inspiration-inhibiting Hering-Breuer reflex. The state of this reflex before and after GABA administration was assessed in terms of the extent of changes in the duration and amplitude of inspiratory oscillations in intrathoracic pressure in response to end-expiratory occlusion of the trachea. Administration of 20 microM GABA into the lateral ventricles of the brain decreased the minute ventilation (due to reductions in the respiratory frequency and respiratory volume), weakened respiratory muscle contractions, and decreased the peak airflow rate on inspiration and expiration. The response to end-expiratory occlusion decreased significantly after administration of GABA, demonstrating the involvement of GABAergic mechanisms in mediating the inspiration-inhibiting Hering-Breuer reflex.

Cortical control of Hering-Breuer reflexes in anesthetized rats.

It had been hypothesized that the regions of prefrontal cortex which are involved in respiratory control can modulate Hering-Breuer reflexes evoked by vagal input from pulmonary stretch receptors. In the present study, experiments were performed on urethane anesthetized spontaneously breathing Wistar rats. The expiratory-promoting reflex was evaluated from changes in expiratory time immediately after airway occlusion at the end of inspiration. The inspiratory-inhibitory reflex was estimated from changes in inspiratory time provoked by airway occlusion at the end of expiration. The results indicate that electrical microstimulation of the responsive sites within the insular cortex significantly weakened both expiratory-promoting and inspiratory-inhibitory reflex. Activation of the infralimbic cortex depressed expiratory-promoting reflex, but inspiratory-inhibitory reflex was enhanced. These results suggest that stimulation of the prefrontal cortex influences vagally mediated control of the respiratory phases timing and several regions of the prefrontal cortex modulate distinct sets of neurons in the network controlling inspiratory and expiratory phases of a breath cycle.

[Effects of gamma-aminobutyric acid on the Hering-Breuer inspiratory-inhibitory reflex].

In acute experiments on rats, effects of cerebro-ventricular microinjections of the gamma-aminobutyric acid (GABA) in the ventilation and Hering-Breuer inspiratory-inhibitory reflex were studied. Alteration of this reflex was estimated by changing in amplitude and duration of the esophageal pressure inspiratory oscillations after tracheal occlusion which was made at the moment of the end of expiration. It has been found that injection of 20 microM of GABA into the lateral ventricle produced a decrease of ventilation in result of diminished respiratory rate and tidal volume and weakening of the inspiratory muscle contractions. The GABA injection significantly decreased the respiratory response to occlusion and therefore it seems that GABA receptors take part in the Hering-Breuer inspiratory-inhibitory reflex.

[Structure of the insular area in the rat cerebral neocortex]. / Stroenie insuliarnoi oblasti novoi kory mozga krysy.

The cytoarchitectonics of brain insular area was studied in albino rat. It was found that this part of neocortex is subdivided into two subareas, each consisting of two fields. The peculiar features of cytoarchitectonics of these subareas and fields are presented. A topographic map is suggested, describing their position on the lateral surface of cerebral hemisphere. Classification of insular area subdivisions, suggested in the present study, is discussed in connection with the data of other authors.

Identification of a respiratory related area in the rat insular cortex.

The aim of this study was to map areas within the rat insular cortex from which respiratory responses originate and compare those sites with gastrointestinal control regions. The insular cortex was systematically microstimulated and histological location of responsive sites determined. Increased inspiratory airflow and decreased respiratory cycle duration were considered to be respiratory excitatory responses. The responses were localized in dysgranular and agranular insular cortex at levels caudal to the joining of the anterior commissure. More rostrally, respiratory inhibitory responses were elicited: these were manifested as a decrease in inspiratory airflow without a significant alteration in respiratory cycle duration. Respiratory inhibitory responses were usually accompanied by changes in gastric motility. These results suggest that the respiratory area in the rat insular cortex consist of two distinct zones which overlap a region modulating the gastrointestinal activity.

[Visceral field of the rat insular cortex]. / Vitseral'noe pole insuliarnoi oblasti kory mozga krys.

Structural-functional organisation of the cortical insular area relating to processes of the visceral functions control, was analysed. Representation of gastrointestinal, respiratory, and cardiovascular systems in the area, is given. Sites of respective neuronal groups and specifics of their spatial organisation within the area, were found. The data obtained suggest a scheme of the rat insular cortex's visceral field.

[The neurons of the medial vestibular nucleus initiating the relaxation of the rat's stomach wall]. / Neirony medial'nogo vestibuliarnogo iadra, initsiiruiushchie relaksatsiiu stenki zheludka u krys.

In acute rat experiments the technique of retrograde axonal transport of horseradish peroxidase in the medial vestibular nucleus allowed to identify a group of neurones sending axons to the "stomach" region of a single tract nucleus. These neurones and, accordingly, the descending vestibular/solitary links can be viewed as the morphologic basis for vestibular influences on the gastric motor activity. As was shown, local irritation of the neurones initiates relaxation of the stomach wall. Activation of the anterior limbic cortex modulates the vestibular/autonomous responses of the intragastric pressure reduction. Irritation of the infralimbic cortex of the rat's brain may have a preventive effect on the stomach wall relaxation stimulated by the vestibular neurones projecting on the "stomach" region of single tract nucleus.

[Effects of the local stimulation of the insular cortex on respiration in rats]. / Respiratornye éffekty lokal'nogo razdrazheniia insuliarnoi kory golovnogo mozga krysy.

Two distinct patterns of respiratory responses to electrical microstimulation were elicited from the rat insular cortex: a decrease in respiratory airflow and tidal volume with no alteration of the respiratory rate (the inhibition response) and an increase in respiratory rate and inspiratory airflow (the excitation response). Gastric motility changes could also be elicited from the anterior insular cortex simultaneously with the inhibition response. The data suggests overlapping of the inhibition response area in the anterior insular cortex with a gastrointestinal representation there, and of the excitation response area in the posterior insular cortex with a cardiovascular representation.

Gastric related neurons in the rat medial vestibular nucleus.

Some structural and functional peculiarities of the rat vestibular nuclei neurones involved in realisation of vestibular-gastrointestinal reflectory reactions were studied. After microinjection of a horseradish peroxidase solution in the 'gastric' area of the nucleus tractus solitarius, retrogradely-labelled cell bodies were found in caudal part of the medial vestibular nucleus. Electrical stimulation of these neurons resulted in the decrease of gastric tone. The respiratory arrest was registered simultaneously. The results suggest that activation of the identified vestibular neurons can induce coordinated changes in visceral systems which are peculiar to a vomiting reaction.

[Interdigestive stomach motor activity in dogs during stimulation of the duodenal receptors by sodium oleate]. / Mezhpishchevaritel'naia motornaia aktivnost' zheludka u sobak pri stimuliatsii retseptorov dvenadtsatiperstnoi kishki oleatom natriia.

Administration of 20% sodium oleate solution in the duodenum of awake dogs suppresses stomach contractions and decreases duration of the postprandial motor complex. Benzohexonium eliminates these oleate effects. The findings suggest that the oleate activates cholinergic vago-vagal reflex which modifies the postprandial motor complex.