The effects of opiates on the respiratory activity of thoracic motoneurones in the anaesthetized and decerebrate rabbit.

Howard, Robin S.; Sears, T. A.

doi:10.1113/jphysiol.1991.sp018590

Cited by 27 publications

(25 citation statements)

References 44 publications

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“…wall, which allows "the bulbospinal output to express the prevailing balance of tonic inspiratory or expiratory drives to the motoneurons, with the expiratory drive dominant" (12). Furthermore, low clinical doses of opiates can indeed produce rigidity in rib cage and abdominal muscles of humans (25, 8a), However, the result of the present study does not establish a priori that D 1 R agonists will be effective against opiate reduction of chest wall compliance.…”

Section: Discussioncontrasting

confidence: 51%

“…Another issue investigated was whether or not D 1 R agonists alleviate opioid-evoked tonic discharges of caudal medullary expiratory neurons, an effect that was previously observed in pentobarbital-anesthetized and unanesthetized decerebrate cats (16), in chloralose-anesthetized dogs (18) and in motor nerve fibers that innervate the expiratory muscles of the chest wall in decerebrate rabbits (12). Because caudal medullary expiratory neurons provide excitatory synaptic drive to expiratory motoneurons (19), prevention of tonic discharges by D 1 R agonists would suggest effectiveness against chest wall rigidity caused by opiates…”

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confidence: 99%

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D₁-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

Lalley¹

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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A previous study in this laboratory showed that dopamine-D1 receptor (D1R) agonists restored phrenic nerve activity after arrest by fentanyl in immobilized, mechanically ventilated cats. The reinstated phrenic nerve rhythm was slower than control, so it was not known whether D1R agonists can restore spontaneous breathing to levels that provide favorable alveolar gas exchange and blood oxygenation. It was also not known whether the agonists counteract opioid analgesia. In the present study, anesthetized, spontaneously breathing cats were given intravenous doses of fentanyl (18.0 Ϯ 3.4 g/kg) that severely depressed depth and rate of respiration, lowered arterial hemoglobin oxygenation (HbO2), elevated end-tidal carbon dioxide (ETCO2), and abolished the nociceptive hind limb crossed-extensor reflex. Fentanyl (30 g/kg) also evoked tonic discharges of caudal medullary expiratory neurons in paralyzed mechanically ventilated cats, which might explain decreased chest compliance. The selective D1R agonists 6-chloro APB (3 mg/kg) or dihydrexidine (DHD, 1 mg/kg) increased depth and rate of spontaneous breathing after opioid depression and returned HbO2 and ETCO2 to control levels. Opioid arrest of the nociceptive reflex remained intact. Pretreatment with DHD prevented significant depression of spontaneous breathing by fentanyl (17.5 Ϯ 4.3 g/kg). Tonic firing evoked by fentanyl in expiratory neurons was converted to rhythmic respiratory discharges by DHD (1 mg/kg). The results suggest that D1R agonists might be therapeutically useful for the treatment of opioid disturbances of breathing without impeding analgesia. expiratory neuron discharges; fentanyl; nociceptive reflex; phrenic nerve activity; respiration and ventilation OPIATES ARE AMONG THE OLDEST and most frequently used drugs for the alleviation of pain, coughing, and smooth muscle spasticity. However, their therapeutic effects are produced at a cost to breathing. Tidal volume and gas exchange are depressed, and respiration is slowed or arrested after an opiate overdose. Therapeutic doses of opiates blunt respiratory responsiveness to carbon dioxide (32,13,28,9), but normal breathing and ventilation are maintained in most individuals because carotid body and medullary chemoreceptors are further stimulated by elevated CO 2 and a consequent acid shift in pH of the arterial blood and extracellular fluid (27, 13). On the other hand, in some patients with renal, pulmonary and cardiac diseases, CO 2 desensitization predisposes them toward respiratory depression by normal doses of opiates (5, 6). In addition, fentanyl and its derivatives can impair ventilation during and after surgery by inducing chest wall rigidity (8a, 25)Opiate receptor antagonists such as naloxone counteract respiratory effects of opioids, but they also block analgesia (5a). They can also produce hypertension, tachycardia, ventricular arrhythmias, and pulmonary edema (9). Thus novel pharmacological approaches are sought that will preserve the therapeutic usefulness of opiates, particularly analgesia, wi...

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Section: Discussioncontrasting

confidence: 51%

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confidence: 99%

D₁-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

Lalley¹

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Opiate slowing of respiratory rhythm, leading to arrest of breathing after the highest doses, has been the topic of many experimental investigations (2,10,14,16,22,24,30,34,37,48,52,60). According to most recent studies, rhythm slowing seems to be principally related to depression of inspiratory interneurons in the pre-Bötzinger complex (PBC) (15, 34, 37), a region within the ventrolateral respiratory column (VRC) that seems to be critical for generation of respiratory rhythm (40, 52).…”

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confidence: 99%

Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons

Lalley¹

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Lalley, Peter M. Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons. Am J Physiol Regul Integr Comp Physiol 290: R1387-R1396, 2006. First published November 10, 2005 doi:10.1152/ajpregu.00530.2005.-Opiates have effects on respiratory neurons that depress tidal volume and air exchange, reduce chest wall compliance, and slow rhythm. The most dose-sensitive opioid effect is slowing of the respiratory rhythm through mechanisms that have not been thoroughly investigated. An in vivo dose-response analysis was performed on medullary respiratory neurons of adult cats to investigate two untested hypotheses related to mechanisms of opioid-mediated rhythm slowing: 1) Opiates suppress intrinsic conductances that limit discharge duration in medullary inspiratory and expiratory neurons, and 2) opiates delay the onset and lengthen the duration of discharges postsynaptically in phase-regulating postinspiratory and late-inspiratory neurons. In anesthetized and unanesthetized decerebrate cats, a threshold dose (3 g/kg) of the -opioid receptor agonist fentanyl slowed respiratory rhythm by prolonging discharges of inspiratory and expiratory bulbospinal neurons. Additional doses (2-4 g/kg) of fentanyl also lengthened the interburst silent periods in each type of neuron and delayed the rate of membrane depolarization to firing threshold without altering synaptic drive potential amplitude, input resistance, peak action potential frequency, action potential shape, or afterhyperpolarization. Fentanyl also prolonged discharges of postinspiratory and late-inspiratory neurons in doses that slowed the rhythm of inspiratory and expiratory neurons without altering peak membrane depolarization and hyperpolarization, input resistance, or action potential properties. The temporal changes evoked in the tested neurons can explain the slowing of network respiratory rhythm, but the lack of significant, direct opioid-mediated membrane effects suggests that actions emanating from other types of upstream bulbar respiratory neurons account for rhythm slowing.fentanyl; medullary respiratory neurons; phrenic nerve activity; naloxonazine; naltrindole OPIATES ARE WELL KNOWN for their ability to depress ventilation by slowing breathing frequency and reducing tidal volume, gas exchange, upper airway patency, and chest wall compliance (3,4,36,39). They also blunt respiratory network responsiveness to hypoxia and CO 2 /acidosis (11,25,51,60).Opiate slowing of respiratory rhythm, leading to arrest of breathing after the highest doses, has been the topic of many experimental investigations (2,10,14,16,22,24,30,34,37,48,52,60). According to most recent studies, rhythm slowing seems to be principally related to depression of inspiratory interneurons in the pre-Bötzinger complex (PBC) (15, 34, 37), a region within the ventrolateral respiratory column (VRC) that seems to be critical for generation of respiratory rhythm (40, 52). However, endogenous opioid peptides are distributed throughout the bulbar respiratory ...

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“…Qualitatively, the effects of opioids on breathing in other mammals appear to be similar to humans, with respiratory rate and MV more depressed than TV, especially in anesthetized preparations (280,580,597,785). However, on a per weight basis, much larger doses of opioids are required in animals than in humans, especially in small mammals, that is, rodents (117,378,722).…”

Section: General Effects On Ventilation: Tidal Volume Respiratory Ramentioning

confidence: 82%

Effects of Anesthetics, Sedatives, and Opioids on Ventilatory Control

Stuth

Stucke

Zuperku

2012

Comprehensive Physiology

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This article provides a comprehensive, up to date summary of the effects of volatile, gaseous, and intravenous anesthetics and opioid agonists on ventilatory control. Emphasis is placed on data from human studies. Further mechanistic insights are provided by in vivo and in vitro data from other mammalian species. The focus is on the effects of clinically relevant agonist concentrations and studies using pharmacological, that is, supraclinical agonist concentrations are de-emphasized or excluded.

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The effects of opiates on the respiratory activity of thoracic motoneurones in the anaesthetized and decerebrate rabbit.

Abstract: SUMMARY1. Efferent discharges were recorded from inspiratory and expiratory intercostal nerve filaments (T2-T10) in artificially ventilated, anaesthetized or decerebrate rabbits with or without vagotomy.

Cited by 27 publications

References 44 publications

D₁-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

D₁-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons

Effects of Anesthetics, Sedatives, and Opioids on Ventilatory Control

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The effects of opiates on the respiratory activity of thoracic motoneurones in the anaesthetized and decerebrate rabbit.

Abstract: SUMMARY1. Efferent discharges were recorded from inspiratory and expiratory intercostal nerve filaments (T2-T10) in artificially ventilated, anaesthetized or decerebrate rabbits with or without vagotomy.

Cited by 27 publications

References 44 publications

D1-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

D1-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons

Effects of Anesthetics, Sedatives, and Opioids on Ventilatory Control

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Product

Resources

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D₁-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

D₁-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat