Experimental model of apneusis and periodic breathing

Tarakanov, I. A.; Сафонов, В. А.; Semkina, G. A.; Golovatyuk, E. A.

doi:10.1007/bf00790047

Cited by 3 publications

(4 citation statements)

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“…In complete agreement with our previous f'mdings [3], sodium oxybutyrate in a dose of 60 ixmol/kg (7 cats) caused periodic respiration, which lasted for 30-40 rain and was followed by spontaneous restoration of a rhythmic pattern of respiratory movements, although the respiratory rate remained greatly reduced; MV was decreased while the respiratory volume was slightly increased. Such respiratory parameters were recorded for 2 to 3 h (Fig.…”

Section: Resultssupporting

confidence: 88%

“…By blocking the central N-cholinergic receptors, tubocurarine abolishes the inhibition of respiratory movements induced through activation of the GABA-ergic system. Key Words: cholinergic system; regulation of respiration; sodium oxybutyrate; tubocurarine; ethanol; GABA The relatively high concentration of gamma-butyric acid (GABA) found at the respiratory center [2,12] and its pronounced inhibitory effects following systemic or central administration to warmblooded animals indicate that GABA participates in the regulation of respiration [3][4][5]10]. The inhibition of respiratory activity by ethanol is also believed to involve the GABA-ergic system [9].…”

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Role of the central N-cholinergic receptors in preventing the inhibition of respiration following activation of the GABA-ergic system in the brain

1995

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Experiments with Nembutal-anesthetized cats, in which sodium oxybutyrate, tubocurarine, and ethyl alcohol are injected into the fourth ventricle of the brain, show that the respiratory disorders caused by sodium oxybutyrate or ethyl alcohol can be eliminated by tubocurarine. By blocking the central N-cholinergic receptors, tubocurarine abolishes the inhibition of respiratory movements induced through activation of the GABA-ergic system. Key Words: cholinergic system; regulation of respiration; sodium oxybutyrate; tubocurarine; ethanol; GABA The relatively high concentration of gamma-butyric acid (GABA) found at the respiratory center [2,12] and its pronounced inhibitory effects following systemic or central administration to warmblooded animals indicate that GABA participates in the regulation of respiration [3][4][5]10]. The inhibition of respiratory activity by ethanol is also believed to involve the GABA-ergic system [9]. The N-cholinergic system, too, takes part in the regulation of respiration, as is evidenced by the presence of Ncholinergic receptors in central structures of the respiratory apparatus, by the relationship of these receptors to GABA-ergic neurons, and by their strong inhibitory influence on respiration when these neurons are activated [4,10,11]. However, the involvement of the GABA-ergic system in the regulation of respiration in comparison with that of the cholinergic system remains unexplored.This study was undertaken to examine the role of the central N-cholinergic receptors in prevent- MATERIALS AND METHODSThe study was conducted on 53 tracheotomized cats (body weight 2.5-3.5 kg) under Nembutal anesthesia (40 mg/kg intraperitoneaUy). Respiratory rate, minute volume (MV), arterial pressure, and heart rate were recorded and averaged using a surgical monitor. Parameters of systemic hemodynamics were registered by means of a catheter inserted into the femoral artery. Respiratory volume was calculated as the ratio of MV to respiratory rate. Electromyograms of the phrenic muscle were taken with an M-42 electromyograph (Hungary) using bipolar metal electrodes. The GABA-ergic system was activated with sodium oxybutyrate. Oxybutyrate at 60 or 180 ~tmol/kg, tubocurarine at 130 or 300 nmol/kg, and 96% ethanol at 330 nmol/kg were injected into the fourth ventricle of the brain in a volume of 50 (the oxybutyrate and tubocurarine were dissoNed in isotonic NaCI solution and 48% ethanol, respectively). Control cats received isotonic NaC1 solution and 48% alcohol in the same volume.

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confidence: 88%

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confidence: 99%

Role of the central N-cholinergic receptors in preventing the inhibition of respiration following activation of the GABA-ergic system in the brain

1995

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“…A similar interrelationship of respiratory and cardiac periodicities was observed in our previous experiments where sodium oxybutyrate or baclofen were used to activate the GABA-ergic system [1,3,4]. Figures 2 and 3 depict typical tracings for the latter two drugs so that their effects on respiration and hemodynamics can be compared with those of phenibut.…”

Section: Resultssupporting

confidence: 54%

Effect of phenibut on the formation of the respiratory rhythm

Tarakanov

Сафонов

1995

Bull Exp Biol Med

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In experiments with Nembutal-anesthetized cats of both sexes, the drug phenibut administered intravenously was found to elicit periodic apneic respiration and to rank between baclofen and sodium oxybutyrate in terms of the ability to disrupt the respiratory rhythm. It is suggested that these three activators of the gamma-aminobutyric acid (GABA) system produce differential effects on GABA~ receptors (baclofen>phenibut>oxybutyrate in order of decreasing effectiveness) and participate in the formation of the respiratory rhythm, and that in activating this system they can give rise to irregular slowed respiration with pauses at inspiration. The structure and function of the brain's GABAergic system remain a subject of sustained interest in view of the important role this system plays in directing a variety of bodily functions. As studies continue to appear, more and more substances are found to be involved in regulating the metabolism and actions of GABA. The GABA-ergic system is of paramount importance for ensuring normal operation of the mechanisms regulating respiration [5,6]. In particular, as we have shown [1], GABA agonists such as sodium oxybutyrate and baclofen, administered systemically or centrally, impede the formation of the respiratory rhythm and the transmission of afferent impulses from pulmonary mechanoreceptors via the vagus nerves to neurons of the respiratory center.The purpose of the present study was to see how selected respiratory parameters and the associated systemic hemodynamic parameters might be affected by phenibut -a substance that shares with sodium oxybutyrate and baclofen the property of being a GABA-ergic system stimulator but differs from them in molecular structure and affinity for specific receptors. MATERIALS AND METHODSThe study was conducted on Nembutal-anesthetized (40 mg/kg intraperitoneally) mongrel cats of both sexes weighing 2.2-3.6 kg. Phenibut was injected intravenously at 100 mg/kg. Dissection details and the procedure used to measure vital parameters are described in our earlier articles [1,4]. RESULTSPhenibut, like the other two stimulants of the GABA-ergic system (sodium oxybutyrate and baelofen), led to a periodic apneic respiration with pauses at inspiration. Typical time courses of the respiratory and systemic hemodynamic parameters after phenibut administration are shown in Fig. 1; it can be seen that respiratory movements became slowed shortly postinjection, this being followed by the appearance of an abnormal respiratory rhythm by minutes 10-15. Respiratory pauses in places where respiratory movements were slowed became increasingly more frequent and reached their maxi-

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“…The presence of N-cholinergic receptors in brainstem structures involved in the regulation of respiration [3,9] indicates that these receptors may be implicated in mediating the effects of lobeline and tubocurarine on respiration. As shown in a number of studies, the GABA A receptors located on the ventral sur-…”

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confidence: 98%

Involvement of the GABA-ergic and N-cholinergic systems in the establishment of terminal respiration

1995

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In experiments with Nembutal-anesthetized cats, in which lobeline, picrotoxin, tubocurarine, and naloxone were injected into the fourth brain ventricle, respiratory disturbances resulting from activation of the central N-cholinergic receptors by lobeline injected when central GABA A receptors were blocked by picrotoxin led to respiration of the gasping type. After naloxone was administered additionally, the normal rhythmic pattern of breathing was restored.Key Words: regulation of respiration; lobeline; picrotoxin; tubocurarine; naloxone; GABAergic and cholinergic systems Blockade of the central N-cholinergic receptors with tubocurarine has been shown to abolish the inhibition of respiratory activity caused by sodium oxybutyrate (or by ethanol), indicating that the cholinergic system is actively involved in the regulation of respiration [2]. It has also been found that N-cholinergic receptors exist at the respiratory center and that GABA-ergic and cholinergic neurons are sequentially linked in certain brain regions [4,9,[11][12][13].The present study was designed to explore the interrelationship between the central N-cholinergic and GABA receptors during the formation of the respiratory rhythm and, in particular, the development of terminal respiration. MATERIALS AND METHODSThe study was conducted on 68 cats (body weight 2.5-4.0 kg) under Nembutal anesthesia (40 mg/kg intraperitoneally) [21. Lobeline at 800 nmol/kg or 3-4 gmol/kg, picrotoxin at 30 nmol/kg, tubocurarine at 130 nmol/kg, and naloxone at 20 nmol/kg were injected into the fourth ventricle of the brain in a volume of 50 p.1 (lobeline and naloxone in isotonic NaC1 solution and picrotoxin and tubocurarine in 48% ethanol). In control tests, isotonic NaC1 solution and 48% ethanol were similarly administered in the same volume as above (the effects from control injections are described in the preceding article [2]). Preliminarily, the carotid nerves were cut to denervate the carotid sinuses and thus prevent the respiratory effect of lobeline on the peripheral N-cholinergic receptors of carotid body cells. The cats were tracheotomized in order to record respiratory parameters and institute artificial ventilation. RESULTSIn tests on 10 cats, designed to see how lobeline would affect respiration under normal conditions, injection of this drag at 800 nmol/kg was followed within 1 min by a sharp decrease in minute volume (MV) as a result of falls in both respiratory rate and respiratory volume, to the point of respiratory arrest for 10-15 min (the cats were on artificial ventilation during that period); 50 to 60 min after lobeline injection, spontaneous respiratory movements were restored and the respiratory rate and volume reached their baseline values (Fig.

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Experimental model of apneusis and periodic breathing

Cited by 3 publications

References 5 publications

Role of the central N-cholinergic receptors in preventing the inhibition of respiration following activation of the GABA-ergic system in the brain

Role of the central N-cholinergic receptors in preventing the inhibition of respiration following activation of the GABA-ergic system in the brain

Effect of phenibut on the formation of the respiratory rhythm

Involvement of the GABA-ergic and N-cholinergic systems in the establishment of terminal respiration

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