Inspiration-promoting vagal reflex under NMDA receptor blockade in anaesthetized rabbits. (9/947)

1. This study describes a novel vagal respiratory reflex in anaesthetized rabbits. In contrast to the well-known inspiratory (I) off-switching by vagal afferent excitation, this vagal reflex initiates and maintains the central I activity of phrenic nerve discharges in rabbits pre-treated with antagonists of N-methyl-D-aspartate-type excitatory amino acid receptors (NMDA-Rs). 2. Under NMDA-R blockade with either dizocilpine (0.025-0.3 mg kg-1), D-2-amino-5-phosphonopentanoic acid (AP5, 0.5-1 mg, i.c.v.) or ketamine (10 mg kg-1), vagal stimulation at low frequencies (5-40 Hz) during the I phase prevented or markedly delayed the spontaneous I termination. In contrast, stimulation of the same vagal afferent at the same intensity but at a higher frequency (100-160 Hz) during the I phase immediately terminated the I phase. 3. In non-vagotomized rabbits, maintaining the tidal volume at end-expiratory levels during the I phase prevented spontaneous I termination and maintained apneusis after NMDA-R blockade with dizocilpine. 4. Brief stimulation of vagal afferents at low frequency (5-40 Hz) during the expiratory (E) phase constantly initiated phrenic I discharge after NMDA-R block. 5. We conclude that low-frequency discharge of vagal pulmonary stretch receptor afferents, as when lung volume is near functional residual capacity, promotes central I activity under NMDA-R blockade.  (+info)

The effects of specific antibody fragments on the 'irreversible' neurotoxicity induced by Brown snake (Pseudonaja) venom. (10/947)

Brown snake (Pseudonaja) venom has been reported to produce 'irreversible' post synaptic neurotoxicity (Harris & Maltin, 1981; Barnett et al., 1980). A murine phrenic nerve/diaphragm preparation was used to study the neurotoxic effects of this venom and pre- and post-synaptic components were distinguished by varying the temperature and frequency of nerve stimulation. There were no myotoxic effects and the neurotoxicity proved irreversible by washing alone. The effects of a new Fab based ovine antivenom have been investigated and proved able to produce a complete, rapid (< 1 h) reversal of the neurotoxicity induced by Brown snake venom. A reversal was also possible when the antivenom addition was delayed for a further 60 min. We believe that this is the first time such a reversal has been shown.  (+info)

Contribution of peripheral chemoreception to the depression of the hypoxic ventilatory response during halothane anesthesia in cats. (11/947)

BACKGROUND: The effects of inhalational anesthetics on the hypoxic ventilatory response are complex. This study was designed to determine the contribution of peripheral chemoreception to the depression of hypoxic ventilatory response seen with halothane anesthesia. METHODS: Cats were anesthetized with pentobarbital sodium and alpha-chloralose and artificially ventilated. Respiratory output was evaluated by phasic inspiratory activity of the phrenic nerve. In 12 cats, this activity was measured during inhalation of an hypoxic gas mixture with halothane, 0, 0.1, and 0.8%, with intact or denervated carotid bodies. In 10 cats, a carotid body was isolated from the systemic circulation and perfused with hypoxic Krebs-Ringer solution equilibrated with halothane, 0, 0.1, and 0.8%. RESULTS: The hypoxic ventilatory response was depressed in a dose-dependent manner during halothane anesthesia. In carotid body perfusion studies, the response was significantly depressed only with halothane, 0.80%. CONCLUSION: The hypoxic ventilatory response is depressed by a high dose of halothane through a peripheral effect at the carotid body.  (+info)

Role of the Botzinger complex in fastigial nucleus-mediated respiratory responses. (12/947)

We have reported that the phrenic neurogram (PN) is modulated by stimulation of the fastigial nucleus (FN) of the cerebellum. The present study was undertaken to search for brainstem site(s) involved in the FN efferent pathway to modulate phrenic nerve activities. Experiments were performed on 35 anesthetized, paralyzed, and ventilated cats, using the PN as the index of the respiratory motor output. Results showed that bilateral electrolytic lesions of the red nucleus (RN), the paramedian reticular nucleus (PRN), or the pontine respiratory group (PRG) had little effect on the ability of FN stimulation to modulate the respiratory output. However, the modulation was abolished by bilateral electrolytic lesions of the Botzinger complex (BotC). Further studies showed that bilateral chemical inactivation of BotC neurons produced by topical microinjection of kainic acid or cobalt chloride failed to abolish the modulation. We concluded that fibers of passage, not synapses or cell bodies in the BotC, were involved in the modulatory effect of FN stimulation on the PN. The RN, PRN, and PRG appear not to be important in the neural circuitry responsible for the FN modulation of the phrenic activity.  (+info)

Rhythmicity in single fiber postganglionic activity supplying the rat tail. (13/947)

Rhythmicity in single fiber postganglionic activity supplying the rat tail. The temporal pattern of ongoing sympathetic vasoconstrictor activity may play an important role for neurovascular transmission. Here we analyzed the activity of postganglionic fibers projecting into the ventral collector nerve of anesthetized and artificially ventilated vagotomized Wistar rats with respect to the presence of rhythmic firing under normocapnic conditions. Most of the fibers studied were likely vasoconstrictor and involved in thermoregulation. Accumulated histograms of sympathetic activity were produced synchronized with the electrocardiogram to detect cardiac rhythmicity, with phrenic nerve activity to detect modulation with the central respiratory cycle, and with tracheal pressure to uncover a reflex modulation associated with artificial ventilation. Sympathetic activity, phrenic activity, and tracheal pressure also were examined by spectral analysis and autocorrelation to detect rhythmicities distinct from respiration. Twenty-seven filaments containing two to seven fibers with spontaneous activity and 51 single fibers were analyzed. Ongoing activity was 1.12 +/- 0.65 imp/s (mean +/- SD, n = 51); conduction velocity was 0.62 +/- 0.06 m/s (n = 30). Cardiac rhythmicity in sympathetic activity was weak (46.2 +/- 16.4%). The dominant rhythm in the activity of 19/27 few-fiber preparations and 37/51 single fibers corresponded to the central respiratory cycle. The pattern consisted of an inhibition during inspiration and an activation in expiration. In 10/19 few-fiber preparations and 21/37 single fibers of this group, there was also a concomitant, less prominent rhythm related to artificial ventilation. By contrast, 8/27 few-fiber preparations and 11/51 single fibers exhibited a dominant pump-related modulation, whereas phrenic-related rhythmicity was subordinate. The dominant rhythm in the activity of two single fibers was related to neither central respiration nor artificial ventilation. We conclude that the ongoing activity of most postganglionic neurons supplying the rat tail is modulated by the central respiratory rhythm generator, suggesting that changes in respiratory drive may alter perfusion of the tail and therefore heat dissipation. Reflex modulation in parallel with artificial ventilation, independent of vagal afferents and possibly due to ventilatory changes of baroreceptor activity, is also an important source of rhythmicity in these neurons.  (+info)

Central CO2 chemoreception: a mechanism involving P2 purinoceptors localized in the ventrolateral medulla of the anaesthetized rat. (14/947)

1. The involvement of P2 purinoceptors in chemosensory function in the ventrolateral regions of the medulla oblongata was investigated in the anaesthetized rat. We have investigated the effect of antagonizing, or desensitizing, P2 receptors in the retrofacial area of the ventrolateral medulla on factors modifying respiratory activity. 2. Bilateral microinjection of suramin (50 nl, 0.02 M), a P2 purinoceptor antagonist, into the retrofacial area in the artificially ventilated rat reduced resting phrenic nerve discharge. It also markedly affected the response of the phrenic nerve to increases in arterial CO2. Under conditions of hyperoxic, hypocapnic apnoea, the mean threshold for inducing phrenic nerve activity was raised significantly (from an end-tidal CO2 of 2.5 % to 4.5 %, n = 9). 3. In addition, the slope of the respiratory response curve to increases in CO2 was reduced after suramin. A similar effect was observed after desensitization of certain P2X receptors with alphabeta-methyleneATP. As arterial levels of O2 were greater than 100 mmHg, and an equivalent pattern of response was observed in sino-aortically denervated and vagotomized animals, we believe any contribution of the peripheral chemoreceptors to be minimal. 4. Our data suggest that respiratory neurones within the retrofacial area (Botzinger complex) represent part of the central site of action of CO2 on respiration. Moreover, our observations lead us to suggest that CO2-evoked changes in respiration are mediated at least in part by P2X purinoceptors.  (+info)

Effects of experimental cortical seizures on respiratory motor nerve activities in piglets. (15/947)

Airway obstruction at the level of the larynx causes respiratory insufficiency during experimental seizures in spontaneously breathing, anesthetized piglets (T. E. Terndrup and W. E. Fordyce, Pediatr. Res., 38: 61-66, 1995). To investigate further the neural mechanisms of this obstruction, the activities of the phrenic nerve (PH) and the recurrent laryngeal motor branches to the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles were analyzed in 11 anesthetized, vagotomized, paralyzed, and ventilated piglets. After a control recording period, seizures were induced by subcortical penicillin G injections. Compared with baseline conditions, nerve activities became irregular during seizures. Extraneous TA bursts during PH activation were evident in all piglets during seizures. During ictal phases of seizures, the peak integrated activities of the PH and the expiratory component of the PCA, but not TA or inspiratory PCA activities, were significantly decreased compared with interictal phases. During seizures, a significant delay in the onset of the inspiratory component of PCA activation with respect to the onset of the PH was observed. This study helps to explain respiratory impairment during cortical seizures by providing evidence of impaired timing of activation of laryngeal dilator mechanisms and coordination with those activating the diaphragm. Cyclical PH inhibition during high-intensity cortical discharges may provide a secondary mechanism producing respiratory insufficiency during seizures.  (+info)

Distinct subtypes of metabotropic glutamate receptors mediate differential actions on excitability of spinal respiratory motoneurons. (16/947)

Metabotropic glutamate receptors (mGluRs) modulate neuronal function by affecting excitability and altering synaptic transmission. We have shown that the mGluR agonist (1S,3R)-1-amino-1, 3-cyclopentanedicarboxylic acid (1S,3R-ACPD) has multiple actions on phrenic motoneurons (PMNs), including reduction of inspiratory-modulated synaptic currents and an increase of neuronal excitability. We hypothesized that these actions were mediated by different mGluR subtypes. We have now identified the involvement of mGluR subtypes and their roles in modulating the excitability of PMNs and the consequent inspiratory motor output in an in vitro neonatal rat brainstem-spinal cord preparation. Activation of postsynaptic group-I mGluRs increases PMN excitability, associated with the production of an inward current and a decrease in membrane conductance, whereas activation of group-II or group-III mGluRs decreases PMN inspiratory-modulated synaptic current, probably via a presynaptic mechanism. To confirm further the distinction and the involvement of group-I and group-II/-III receptor subtypes affecting PMN excitability, we used the membrane permeable cAMP analog 8-bromo-cAMP (8-Br-cAMP) to elevate intracellular cAMP concentration to mask or occlude any effects mediated via the cAMP cascade. 8-Br-cAMP attenuated the reduction of the inspiratory-modulated activity of PMNs by both (S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG) and L-(+)-2-amino-4-phosphonobutyric acid (L-AP4), agonists for group-II and group-III mGluRs, respectively, but did not affect the actions of 3,5-dihydroxyphenylglycine (DHPG), an agonist for group-I mGluRs. These three groups of mGluRs are all endogenously activated during the inspiratory phase. We conclude that three groups of mGluRs are functionally expressed in the phrenic nucleus and that their activation modulates PMN excitability via distinct mechanisms, with group-I acting at postsynaptic sites and group-II and group-III acting at presynaptic sites.  (+info)