Effects on respiratory pattern of focal cooling in the medulla of the dog

1988 ◽  
Vol 65 (5) ◽  
pp. 2004-2010 ◽  
Author(s):  
M. Adams ◽  
T. Chonan ◽  
N. S. Cherniack ◽  
C. von Euler
Keyword(s):  
Respiratory Rhythm ◽  
Nucleus Ambiguus ◽  
Respiratory Pattern ◽  
Respiratory Drive ◽  
Timing Effect ◽  
Diaphragm Electrical Activity ◽  
Inspiratory Activity ◽  
Ventral Medullary Surface ◽  
Focal Cooling

Studies in cats have shown that, in addition to respiratory neuron groups in the dorsomedial (DRG) and ventrolateral (VRG) medulla, neural structures in the most ventral medullary regions are important for the maintenance of respiratory rhythm. The purpose of this study was to determine whether a similar superficially located ventral region was present in the dog and to assess the role of each of the other regions in the canine medulla important in the control of breathing, in 20 anesthetized, vagotomized, and artificially ventilated dogs, a cryoprobe was used to cool selected regions of the medulla to 15-20 degrees C. Respiratory output was determined from phrenic nerve or diaphragm electrical activity. Cooling in or near the nucleus of the solitary tract altered timing and produced little change in the amplitude or rate of rise of inspiratory activity; lengthening of inspiratory time was the most common timing effect observed. Cooling in ventrolateral regions affected the amplitude and rate of rise of respiratory activity. Depression of neural tidal volume and apnea could be produced by unilateral cooling in two ventrolateral regions: 1) near the nucleus ambiguus and nucleus para-ambiguus and 2) just beneath the ventral medullary surface. These findings indicate that in the dog dorsomedial neural structures influence respiratory timing, whereas more ventral structures are important to respiratory drive.

Mechanoreceptor modulation of endogenous respiratory rhythms in vertebrates

1990 ◽  
Vol 259 (5) ◽  
pp. R898-R910 ◽  
Author(s):  
W. K. Milsom
Keyword(s):  
Breathing Pattern ◽  
Respiratory Rhythm ◽  
Flow Distribution ◽  
Respiratory Pattern ◽  
Respiratory Drive ◽  
Lung Inflation ◽  
Phase Switching ◽  
Separate Control ◽  
Regulation Of Breathing ◽  
Receptor Input

While pulmonary mechanoreceptors appear to play little or no role in determining the eupneic breathing pattern in some species of vertebrates, they do in others as well as in all species under conditions of elevated respiratory drive. Tonic and phasic inputs from this receptor group have independent roles in determining breathing pattern. Thus withholding lung inflation produces very different results from receptor denervation. There are at least five phases to the respiratory cycle that appear to be under separate control. Tonic receptor input is involved primarily in regulating the length of the respiratory pause, which can occur at the end of inspiration or expiration, depending on the species. Phasic receptor input has different effects during different phases of the cycle as well as different effects at different times during a single phase. This activity contributes to phase switching during the ventilation cycle and thus to the regulation of breathing frequency and tidal volume. The significance of the modulatory effects of phasic input on the duration of different phases of the ventilation cycle is not totally clear, but the evidence suggests that phasic input acts to stabilize the respiratory pattern and may be instrumental in optimizing the breathing pattern in terms of ergometric costs. This appears to be the case in all vertebrate classes, despite dramatic differences in the mechanical events associated with ventilation arising from different respiratory pumps. These receptors also appear to have significant roles other than those associated with modulation of respiratory rhythm, particularly in lower vertebrates. Many of these roles, such as maintaining the integrity of the gill curtain in fish or buoyancy control and regulation of blood flow distribution in reptiles, may be as important as their role in modulating the endogenous rhythm.

Species differences in respiratory rhythm generation in rodents

2010 ◽  
Vol 298 (4) ◽  
pp. R887-R898 ◽  
Author(s):  
B. M. Gajda ◽  
A. Y. Fong ◽  
W. K. Milsom
Keyword(s):  
Respiratory Rhythm ◽  
Inhibitory Effect ◽  
Motor Output ◽  
Flufenamic Acid ◽  
Respiratory Drive ◽  
Respiratory Rhythmogenesis ◽  
Young Rats ◽  
Highly Sensitive

We examined the role of riluzole (RIL)- and flufenamic acid (FFA)-sensitive mechanisms in respiratory rhythmogenesis in rats and hamsters using the in situ arterially perfused preparation. Based on the hypothesis that respiratory networks in animals capable of autoresuscitation would have a greater prevalence of membrane mechanisms that promote endogenous bursting, we predicted that older (weaned) hamsters (a hibernating species) would be more sensitive to the blockade of RIL- and FFA-sensitive mechanisms than age-matched rats and that younger (preweaned) rats would behave more like hamsters. Consistent with this, we found that respiratory motor output in weaned hamsters [>21 days postnatal (P21)] was highly sensitive to RIL (0.2–20 μM), while in young rats (P12–14) it was less so (only affected at higher concentrations of RIL), and weaned rats were not affected at all. On the other hand, respiratory motor output was equally reduced by FFA (0.25–25 μM) in both young and weaned rats but was unaffected in weaned hamsters. Coapplication of RIL and FFA (RIL + FFA) produced greater inhibition of respiration in both young and weaned rats compared with either drug alone. In contrast, in weaned hamsters, FFA coapplication offset the inhibitory effect of RIL alone. Increasing respiratory drive with hypercapnia/acidosis ameliorated the respiratory inhibition produced by RIL + FFA in weaned rats but had no effect in young rats. Data from the present study indicate that respiratory rhythmogenesis in young rats is more dependent on excitatory RIL-sensitive and FFA-sensitive mechanisms than older rats and that fundamental differences exist in the respiratory rhythmogenic mechanisms between rats and hamsters.

Inspiratory elevation of the ribs in the dog: primary role of the parasternals [published errata appear in J Appl Physiol 1991 Aug;71(2):following Table of Contents and 1991 Dec;71(6):following Author Index]

1991 ◽  
Vol 70 (4) ◽  
pp. 1447-1455 ◽  
Author(s):  
A. De Troyer
Keyword(s):  
Quantitative Analysis ◽  
Axial Displacement ◽  
The Other ◽  
Primary Role ◽  
Intercostal Muscles ◽  
The Third ◽  
Inspiratory Activity ◽  
Fourth Rib

To assess the relative contributions of the different groups of inspiratory intercostal muscles to the cranial motion of the ribs in the dog, we have measured the axial displacement of the fourth rib and recorded the electromyograms of the parasternal intercostal, external intercostal, and levator costae in the third interspace in 15 anesthetized animals breathing at rest. In eight animals, the parasternal intercostals were denervated in interspaces 1-5. This procedure caused a marked increase in the amount of external intercostal and levator costae inspiratory activity, and yet the inspiratory cranial motion of the rib was reduced by 55%. On the other hand, the external intercostals in interspaces 1-5 were sectioned in seven animals, and the reduction in the cranial rib motion was only 22%; the amount of parasternal and levator costae activity, however, was unchanged. When the parasternals in these animals were subsequently denervated, the levator costae inspiratory activity increased markedly, but the inspiratory cranial motion of the rib was abolished or reversed into an inspiratory caudal motion. These studies thus confirm that, in the dog breathing at rest, the parasternal intercostals have a larger role than the external intercostals and levator costae in causing the cranial motion of the ribs during inspiration. A quantitative analysis suggests that the parasternal contribution is approximately 80%.

scholarly journals Site-specific effects on respiratory rhythm and pattern of ibotenic acid injections in the pontine respiratory group of goats

2010 ◽  
Vol 109 (1) ◽  
pp. 171-188 ◽  
Author(s):  
J. M. Bonis ◽  
S. E. Neumueller ◽  
K. L. Krause ◽  
T. Kiner ◽  
A. Smith ◽  
...  
Keyword(s):  
Pulmonary Ventilation ◽  
Respiratory Rhythm ◽  
Ibotenic Acid ◽  
Pattern Generation ◽  
Respiratory Pattern ◽  
Breathing Patterns ◽  
Site Specific ◽  
Specific Effects ◽  
Tegmental Nuclei ◽  
Pontine Respiratory Group

To probe further the contributions of the rostral pons to eupneic respiratory rhythm and pattern, we tested the hypothesis that ibotenic acid (IA) injections in the pontine respiratory group (PRG) would disrupt eupneic respiratory rhythm and pattern in a site- and state-specific manner. In 15 goats, cannulas were bilaterally implanted into the rostral pontine tegmental nuclei (RPTN; n = 3), the lateral (LPBN; n = 4) or medial parabrachial nuclei (MPBN; n = 4), or the Kölliker-Fuse nucleus (KFN; n = 4). After recovery from surgery, 1- and 10-μl injections (1 wk apart) of IA were made bilaterally through the implanted cannulas during the day. Over the first 5 h after the injections, there were site-specific ventilatory effects, with increased ( P < 0.05) breathing frequency in RPTN-injected goats, increased ( P < 0.05) pulmonary ventilation (V̇i) in LPBN-injected goats, no effect ( P < 0.05) in MPBN-injected goats, and a biphasic V̇i response ( P < 0.05) in KFN-injected goats. This biphasic response consisted of a hyperpnea for 30 min, followed by a prolonged hypopnea and hypoventilation with marked apneas, apneusis-like breathing patterns, and/or shifts in the temporal relationships between inspiratory flow and diaphragm activity. In the awake state, 10–15 h after the 1-μl injections, the number of apneas was greater ( P < 0.05) than during other studies at night. However, there were no incidences of terminal apneas. Breathing rhythm and pattern were normal 22 h after the injections. Subsequent histological analysis revealed that for goats with cannulas implanted into the KFN, there were nearly 50% fewer neurons ( P < 0.05) in all three PRG subnuclei than in control goats. We conclude that in awake goats, 1) IA injections into the PRG have site-specific effects on breathing, and 2) the KFN contributes to eupneic respiratory pattern generation.

scholarly journals Feasibility of neurally adjusted positive end-expiratory pressure in rabbits with early experimental lung injury

2021 ◽  
Author(s):  
Ling Liu ◽  
Daijiro Takahashi ◽  
Haibo Qui ◽  
Arthur S. Slutsky ◽  
Christer Sinderby ◽  
...  
Keyword(s):  
Lung Injury ◽  
Electrical Activity ◽  
Esophageal Pressure ◽  
Neurally Adjusted Ventilatory Assist ◽  
Diaphragm Electrical Activity ◽  
New Zealand White Rabbits ◽  
Ventilatory Assist ◽  
Resistive Loading ◽  
Inspiratory Activity ◽  
The Mean

Background During conventional Neurally Adjusted Ventilatory Assist (NAVA), the electrical activity of the diaphragm (EAdi) is used for triggering and cycling-off inspiratory assist, with a fixed PEEP (so called “Triggered Neurally Adjusted Ventilatory Assist” or “tNAVA”). However, significant post-inspiratory activity of the diaphragm can occur, believed to play a role in maintaining end-expiratory lung volume. Adjusting pressure continuously, in proportion to both inspiratory and expiratory EAdi (Continuous NAVA, or cNAVA), would not only offer inspiratory assist for tidal breathing, but also may aid in delivering a “neurally adjusted PEEP”, and more specific breath-by-breath unloading. Methods Nine adult New Zealand white rabbits were ventilated during independent conditions of: resistive loading (RES1 or RES2), CO2 load (CO2) and acute lung injury (ALI), either via tracheotomy (INV) or non-invasively (NIV). There were a total of six conditions, applied in a non-randomized fashion: INV-RES1, INV-CO2, NIV-CO2, NIV-RES2, NIV-ALI, INV-ALI. For each condition, tNAVA was applied first (3 min), followed by 3 min of cNAVA. This comparison was repeated 3 times (repeated cross-over design). The NAVA level was always the same for both modes, but was newly titrated for each condition. PEEP was manually set to zero during tNAVA. During cNAVA, the assist during expiration was proportional to the EAdi. During all runs and conditions, ventilator-delivered pressure (Pvent), esophageal pressure (Pes), and diaphragm electrical activity (EAdi) were measured continuously. The tracings were analyzed breath-by-breath to obtain peak inspiratory and mean expiratory values. Results For the same peak Pvent, the distribution of inspiratory and expiratory pressure differed between tNAVA and cNAVA. For each condition, the mean expiratory Pvent was always higher (for all conditions 4.0 ± 1.1 vs. 1.1 ± 0.5 cmH2O, P < 0.01) in cNAVA than in tNAVA. Relative to tNAVA, mean inspiratory EAdi was reduced on average (for all conditions) by 19 % (range 14 %–25 %), p < 0.05. Mean expiratory EAdi was also lower during cNAVA (during INV-RES1, INV-CO2, INV-ALI, NIV-CO2 and NIV-ALI respectively, P < 0.05). The inspiratory Pes was reduced during cNAVA all 6 conditions (p < 0.05). Unlike tNAVA, during cNAVA the expiratory pressure was comparable with that predicted mathematically (mean difference of 0.2 ± 0.8 cmH2O). Conclusion Continuous NAVA was able to apply neurally adjusted PEEP, which led to a reduction in inspiratory effort compared to triggered NAVA.

scholarly journals Enhancement of Methacholine-Evoked Tracheal Contraction Induced by Bacterial Lipopolysaccharides Depends on Epithelium and Tumor Necrosis Factor

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
T. Secher ◽  
F. Rodrigues Coelho ◽  
N. Noulin ◽  
A. Lino dos Santos Franco ◽  
V. Quesniaux ◽  
...  
Keyword(s):  
Contractile Response ◽  
Ex Vivo ◽  
Adaptor Protein ◽  
Respiratory Pattern ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Bacterial Lipopolysaccharides ◽  
Necrosis Factor

Inhaled bacterial lipopolysaccharides (LPSs) induce an acute tumour necrosis factor-alpha (TNF-α-) dependent inflammatory response in the murine airways mediated by Toll-like receptor 4 (TLR4) via the myeloid differentiation MyD88 adaptor protein pathway. However, the contractile response of the bronchial smooth muscle and the role of endogenous TNFα in this process have been elusive. We determined the in vivo respiratory pattern of C57BL/6 mice after intranasal LPS administration with or without the presence of increasing doses of methacholine (MCh). We found that LPS administration altered the basal and MCh-evoked respiratory pattern that peaked at 90 min and decreased thereafter in the next 48 h, reaching basal levels 7 days later. We investigated in controlled ex vivo condition the isometric contraction of isolated tracheal rings in response to MCh cholinergic stimulation. We observed that preincubation of the tracheal rings with LPS for 90 min enhanced the subsequent MCh-induced contractile response (hyperreactivity), which was prevented by prior neutralization of TNFα with a specific antibody. Furthermore, hyperreactivity induced by LPS depended on an intact epithelium, whereas hyperreactivity induced by TNFα was well maintained in the absence of epithelium. Finally, the enhanced contractile response to MCh induced by LPS when compared with control mice was not observed in tracheal rings from TLR4- or TNF- or TNF-receptor-deficient mice. We conclude that bacterial endotoxin-mediated hyperreactivity of isolated tracheal rings to MCh depends upon TLR4 integrity that signals the activation of epithelium, which release endogenous TNFα.

Phrenic afferents and ventilatory control at increased end-expiratory lung volumes in cats

1989 ◽  
Vol 66 (3) ◽  
pp. 1297-1303 ◽  
Author(s):  
S. Iscoe
Keyword(s):  
Steady State ◽  
Independent Effect ◽  
Respiratory Drive ◽  
Phrenic Motoneurons ◽  
Partial Pressure Of Co2 ◽  
Before And After ◽  
Steady State Responses ◽  
Spontaneously Breathing ◽  
State Responses

The role of phrenic afferents in controlling inspiratory duration (TI) at elevated end-expiratory lung volume (EEV) has been studied in pentobarbital-anesthetized, spontaneously breathing cats with intact vagi. Responses to increases in EEV, induced by imposition of an expiratory threshold load (ETL) of 10 cmH2O, were monitored before and after section of cervical dorsal roots C3-C7. The immediate (first-breath) effect of application of ETL was a prolongation of both TI and expiratory duration (TE). After 10 min of breathing against the ETL, average TI returned to control values but TE remained prolonged. Abolishing feedback from the diaphragm did not affect these responses. When steady-state responses to ETL were compared with those elicited by inhalation of 5–6% CO2 in O2, changes in EEV had, on average, no independent effect on respiratory drive (rate of rise of integrated phrenic activity), although phrenic activity increased greatly in some cats despite little or no change in arterial partial pressure of CO2. These data indicate that diaphragmatic receptors do not contribute to either the immediate (first-breath) or steady-state responses of phrenic motoneurons to increases in EEV in intact cats.

Gap Junctions and Inhibitory Synapses Modulate Inspiratory Motoneuron Synchronization

2001 ◽  
Vol 85 (4) ◽  
pp. 1543-1551 ◽  
Author(s):  
Céline Bou-Flores ◽  
Albert J. Berger
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Time Scale ◽  
Respiratory Rhythm ◽  
Respiratory Frequency ◽  
Glycyrrhetinic Acid ◽  
Inhibitory Synapses ◽  
Short Time Scale ◽  
Inspiratory Activity ◽  
Short Time

Interneuronal electrical coupling via gap junctions and chemical synaptic inhibitory transmission are known to have roles in the generation and synchronization of activity in neuronal networks. Uncertainty exists regarding the roles of these two modes of interneuronal communication in the central respiratory rhythm-generating system. To assess their roles, we performed studies on both the neonatal mouse medullary slice and en bloc brain stem-spinal cord preparations where rhythmic inspiratory motor activity can readily be recorded from both hypoglossal and phrenic nerve roots. The rhythmic inspiratory activity observed had two temporal characteristics: the basic respiratory frequency occurring on a long time scale and the synchronous neuronal discharge within the inspiratory burst occurring on a short time scale. In both preparations, we observed that bath application of gap-junction blockers, including 18α-glycyrrhetinic acid, 18β-glycyrrhetinic acid, and carbenoxolone, all caused a reduction in respiratory frequency. In contrast, peak integrated phrenic and hypoglossal inspiratory activity was not significantly changed by gap-junction blockade. On a short-time-scale, gap-junction blockade increased the degree of synchronization within an inspiratory burst observed in both nerves. In contrast, opposite results were observed with blockade of GABAA and glycine receptors. We found that respiratory frequency increased with receptor blockade, and simultaneous blockade of both receptors consistently resulted in a reduction in short-time-scale synchronized activity observed in phrenic and hypoglossal inspiratory bursts. These results support the concept that the central respiratory system has two components: a rhythm generator responsible for the production of respiratory cycle timing and an inspiratory pattern generator that is involved in short-time-scale synchronization. In the neonatal rodent, properties of both components can be regulated by interneuronal communication via gap junctions and inhibitory synaptic transmission.

Power spectra of inspiratory nerve activity with lung inflations in cats

1988 ◽  
Vol 64 (4) ◽  
pp. 1709-1720 ◽  
Author(s):  
C. A. Richardson
Keyword(s):  
High Frequency ◽  
Power Spectra ◽  
High Peak ◽  
Spectral Peak ◽  
Respiratory Pattern ◽  
Inflation Pressure ◽  
High Frequency Peak ◽  
Lung Inflation ◽  
Consistent Manner ◽  
Inspiratory Activity

To investigate the effect of lung inflations on the high-frequency synchrony (70-122 Hz) observed in the inspiratory activity of respiratory motor nerves of decerebrate cats, I applied a step increase in lung inflation pressure at fixed delays into the inspiratory phase and computed power spectra of phrenic neurograms before and during inflation. In 25 decerebrate paralyzed cats the frequency of the high spectral peak was 92.3 +/- 11.1 Hz before and 105.3 +/- 12.1 Hz during the step in inflation pressure, shifting upward by 13.0 +/- 6.0 Hz. For 8 of the 25 cats, the recurrent laryngeal and phrenic neurograms were recorded simultaneously. The high spectral peak was present during inspiration in the recurrent laryngeal power spectra and coherent with the high peak in the phrenic power spectra. In response to lung inflation, the high peak disappeared from the power spectra of the recurrent laryngeal nerve as the inspiratory activity was inhibited; a shift upward in frequency was not detectable. Comparing inspiratory times (TI, based on the phrenic neurograms) for breaths with no lung inflations to those for breaths with lung inflations, I found that lung inflations early in inspiration caused a decrease in TI, lung inflations at intermediates times had no effect on TI, and lung inflations late in inspiration caused an increase in TI. Despite lung inflation decreasing, not affecting, or increasing inspiratory duration and amplitude of the phrenic neurogram, lung inflation always caused a shift upward in the high-frequency peak of the phrenic power density. The fact that lung inflation, a powerful respiratory stimulus, affected the frequency of the high peak in a consistent manner suggests that the high-frequency synchrony is an important and robust feature of the central respiratory pattern generator.

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