The “other” respiratory effect of opioids: suppression of spontaneous augmented (“sigh”) breaths

2011 ◽  
Vol 111 (5) ◽  
pp. 1296-1303 ◽  
Author(s):  
Harold J. Bell ◽  
Elizabeth Azubike ◽  
Philippe Haouzi

The purpose of this study was to examine the effects of a clinically relevant opioid on the production of augmented breaths (ABs) in unanesthetized animals breathing normal room air, using a dosage which does not depress breathing. To do this we monitored breathing noninvasively, in unrestrained animals before and after subcutaneous injection of either morphine, or a saline control. The effect of ketamine/xylazine was also studied to determine the potential effect of an alternative sedative agent. Last, the effect of naloxone was studied to determine the potential influence of endogenous opioids in regulating the normal incidence of ABs. Morphine (5 mg/kg) had no depressive effect on breathing, but completely eliminated ABs in all animals in room air ( P = 0.027). However, when animals breathed hypoxic air (10% O2), animals did express ABs, although their incidence was still reduced by morphine ( P < 0.001). This was not a result of sedation per se, as ABs continued at their normal rate in room air during sedation with ketamine. Naloxone had no effect on breathing or AB production, and so endogenous opioids are not likely involved in regulating their rate of production under normal conditions. Our results show that in unanesthetized animals breathing normal room air, a clinically relevant opioid eliminates ABs, even at a dose that does not cause respiratory depression. Despite this, hypoxia-induced stimulation of breathing can facilitate the production of ABs even with the systemic opioid present, indicating that peripheral chemoreceptor stimulation provides a potential means of overcoming the opioid-induced suppression of these respiratory events.

1995 ◽  
Vol 73 (01) ◽  
pp. 039-048 ◽  
Author(s):  
A Bierhaus ◽  
Ch J Hemmer ◽  
N Mackman ◽  
R Kutob ◽  
R Ziegler ◽  
...  

SummarySerum from patients with P. falciparum malaria at day 1 (pretherapy) induces tissue factor (TF) in cultured endothelial cells. TF induction depends on de novo transcription as shown in Nuclear Run On assays. Electrophoretic mobility shift assays demonstrated binding of AP-1 and NF- κB/Rel proteins to their recognition sites in the TF promotor. After therapy (day 28), stimulation of TF antigen by patient serum is reduced by 70%. When serum obtained before and after therapy was compared, a decrease of NF-κB activation was evident. Activation of NF-κB-like proteins was in part dependent on TNFα in patient serum, since a TNFα neutralizing antibody reduced induction of TF transcription and translation and induction of NF-κB-like proteins. Induction of TF activity was suppressed by pDTC, an inhibitor of NF-κB activation. When different promotor constructs of the TF gene were tested, induction was dependent upon the presence of the intact NF-κB-like binding site in the TF promotor. A mutant with deleted NF-κB, but intact AP-1 sites was not inducible. Mutation of the AP-1 sites did not prevent induction, but reduced inducibility by pretherapy serum. Therefore, NF-κB/Rel proteins are responsible for induction of TF transcription by pretherapy serum, but AP-1 is needed for highest inducibility. The effect of antiparasitic therapy on the induction of TF by serum from patients with complicated P. falciparum malaria is dependent on a therapy-mediated loss of activation of NF-κB-like proteins in post-treatment patient serum.


2005 ◽  
Vol 288 (6) ◽  
pp. G1195-G1198 ◽  
Author(s):  
Shi Liu ◽  
Lijie Wang ◽  
J. D. Z. Chen

Gastric electrical stimulation (GES) has been shown to alter motor and sensory functions of the stomach. However, its effects on other organs of the gut have rarely been investigated. The study was performed in 12 dogs implanted with two pairs of electrodes, one on the serosa of the stomach and the other on the colon. The study was composed of two experiments. Experiment 1 was designed to study the effects of GES on rectal tone and compliance in nine dogs compared with colonic electrical stimulation (CES). Rectal tone and compliance were assessed before and after GES or CES. Experiment 2 was performed to study the involvement of sympathetic pathway in 8 of the 12 dogs. The rectal tone was recorded for 30–40 min at baseline and 20 min after intravenous guanethidine. GES or CES was given for 20 min 20 min after the initiation of the infusion. It was found that both GES and CES reduced rectal tone with comparable potency. Rectal compliance was altered neither with GES, nor with CES. The inhibitory effect of GES but not CES on rectal tone was abolished by an adrenergic blockade, guanethidine. GES inhibited rectal tone with a comparable potency with CES but did not alter rectal compliance. The inhibitory effect of GES on rectal tone is mediated by the sympathetic pathway. It should be noted that electrical stimulation of one organ of the gut may have a beneficial or adverse effect on another organ of the gut.


2010 ◽  
Vol 28 (3) ◽  
pp. 115-119 ◽  
Author(s):  
Anaflávia O Freire ◽  
Gisele C M Sugai ◽  
Sônia Maria Togeiro ◽  
Luiz Eugênio Mello ◽  
Sérgio Tufik

Background Most patients with obstructive sleep apnoea (OSA) do not tolerate treatment with nasal continuous positive airway pressure, the ‘gold standard’ treatment for this condition. It was shown in a pilot study that acupuncture was more effective than placebo treatment (sham acupuncture) in producing significant changes in the respiratory events assessed by polysomnography (PSG). Objectives To investigate the immediate effect of manual acupuncture (MA) and electroacupuncture (EA) on the sleep pattern of patients presenting with moderate OSA. Methods 40 patients with an Apnoea–Hypopnoea Index (AHI) of 15–30/h were randomly allocated to MA treatment (n=10), EA 10 Hz treatment (n=10), EA 2 Hz treatment (n=10) and a no-treatment control group (n=10). The patients received MA or EA (2 or 10 Hz) just before the PSG study at 20:00. Results The AHI (p=0.005; p=0.005), the Apnoea Index (p=0.038; p=0.009) and the respiratory events (p=0.039; p=0.014) decreased significantly in the MA and EA 10 Hz groups, respectively (AHI (21.9, 11.2), Apnoea Index (5.15, 0.7), respiratory events (120.5, 61.0) in the MA group before and after. AHI (20.6, 9.9), Apnoea Index (8.2, 0.3), respiratory events (117.0, 56.0) in the EA 10 Hz group before and after). The micro-arousals decreased only in the MA group (146.0 vs 88.5, p=0.0002). There were no significant changes in the EA 2 Hz group or in the control group. Conclusion A single session of either MA or EA 10 Hz had an acute effect in reducing the AHI as well as the number of nocturnal respiratory events of patients presenting with moderate OSA.


1992 ◽  
Vol 72 (6) ◽  
pp. 2311-2316 ◽  
Author(s):  
H. Miki ◽  
W. Hida ◽  
Y. Kikuchi ◽  
T. Chonan ◽  
M. Satoh ◽  
...  

We examined the effect of electrical stimulation of the hypoglossal nerve and pharyngeal lubrication with artificial surfactant (Surfactant T-A) on the opening of obstructed upper airway in nine anesthetized supine dogs. The upper airway was isolated from the lower airway by transecting the cervical trachea. Upper airway obstruction was induced by applying constant negative pressures (5, 10, 20, and 30 cmH2O) on the rostral cut end of the trachea. Peripheral cut ends of the hypoglossal nerves were electrically stimulated by square-wave pulses at various frequencies from 10 to 30 Hz (0.2-ms duration, 5–7 V), and the critical stimulating frequency necessary for opening the obstructed upper airway was measured at each driving pressure before and after pharyngeal lubrication with artificial surfactant. The critical stimulation frequency for upper airway opening significantly increased as upper airway pressure became more negative and significantly decreased with lubrication of the upper airway. These findings suggest that greater muscle tone of the genioglossus is needed to open the occluded upper airway with larger negative intraluminal pressure and that lubrication of the pharyngeal mucosa with artificial surfactant facilitates reopening of the upper airway.


2015 ◽  
Vol 114 (5) ◽  
pp. 2672-2681 ◽  
Author(s):  
Emanuel N. van den Broeke ◽  
André Mouraux ◽  
Antonia H. Groneberg ◽  
Doreen B. Pfau ◽  
Rolf-Detlef Treede ◽  
...  

Secondary hyperalgesia is believed to be a key feature of “central sensitization” and is characterized by enhanced pain to mechanical nociceptive stimuli. The aim of the present study was to characterize, using EEG, the effects of pinprick stimulation intensity on the magnitude of pinprick-elicited brain potentials [event-related potentials (ERPs)] before and after secondary hyperalgesia induced by intradermal capsaicin in humans. Pinprick-elicited ERPs and pinprick-evoked pain ratings were recorded in 19 healthy volunteers, with mechanical pinprick stimuli of varying intensities (0.25-mm probe applied with a force extending between 16 and 512 mN). The recordings were performed before (T0) and 30 min after (T1) intradermal capsaicin injection. The contralateral noninjected arm served as control. ERPs elicited by stimulation of untreated skin were characterized by 1) an early-latency negative-positive complex peaking between 120 and 250 ms after stimulus onset (N120-P240) and maximal at the vertex and 2) a long-lasting positive wave peaking 400–600 ms after stimulus onset and maximal more posterior (P500), which was correlated to perceived pinprick pain. After capsaicin injection, pinprick stimuli were perceived as more intense in the area of secondary hyperalgesia and this effect was stronger for lower compared with higher stimulus intensities. In addition, there was an enhancement of the P500 elicited by stimuli of intermediate intensity, which was significant for 64 mN. The other components of the ERPs were unaffected by capsaicin. Our results suggest that the increase in P500 magnitude after capsaicin is mediated by facilitated mechanical nociceptive pathways.


1994 ◽  
Vol 188 (1) ◽  
pp. 159-174 ◽  
Author(s):  
S Riestenpatt ◽  
W Zeiske ◽  
H Onken

Split gill lamellae (epithelium plus cuticle) of hyperregulating Chinese crabs acclimated to fresh water were mounted in a modified Ussing chamber. Active and electrogenic absorption of sodium and chloride were measured as positive amiloride-sensitive and negative Cl--dependent short-circuit currents (INa, ICl), respectively. Both currents were characterized before and after treatment of the tissue with theophylline or dibutyryl cyclic AMP. Both drugs increased INa and ICl. A simple circuit analysis showed that INa stimulation reflected a marked increase in the transcellular Na+ conductance, whereas the respective electromotive force was unchanged. The Michaelis constant (KNa) for Na+ current saturation was decreased after INa stimulation, indicating an increased affinity of the transport mechanism for its substrate. Consequently, the affinity for the Na+ channel blocker amiloride decreased as expected for a competitive interaction between substrate and inhibitor. Analysis of the amiloride-induced current-noise revealed a marked increase in the number of apical Na+ channels after INa stimulation with theophylline, whereas there was little change in the single-channel current. Stimulation of Cl- absorption was accompanied by a substantial increase in both transcellular conductance and electromotive force, indicating an activation of the apical H+ pump that provides the driving force for active Cl- uptake via apical Cl-/HCO3- exchange and basolateral Cl- channels.


2012 ◽  
Vol 112 (8) ◽  
pp. 1248-1257 ◽  
Author(s):  
Lee Friedman ◽  
Thomas E. Dick ◽  
Frank J. Jacono ◽  
Kenneth A. Loparo ◽  
Amir Yeganeh ◽  
...  

In this work, cardio-ventilatory coupling (CVC) refers to the statistical relationship between the onset of either inspiration (I) or expiration (E) and the timing of heartbeats (R-waves) before and after these respiratory events. CVC was assessed in healthy, young (<45 yr), resting, supine subjects ( n = 19). Four intervals were analyzed: time from I-onset to both the prior R-wave (R-to-I) and the following R-wave (I-to-R), as well as time from E-onset to both the prior R-wave (R-to-E) and following R-wave (E-to-R). The degree of coupling was quantified in terms of transformed relative Shannon entropy (tRSE), and χ2 tests based on histograms of interval times from 200 breaths. Subjects were studied twice, from 5 to 27 days apart, and the test-retest reliability of CVC measures was computed. Several factors pointed to the relative importance of the R-to-I interval compared with other intervals. Coupling was significantly stronger for the R-to-I interval, coupling reliability was largest for the R-to-I interval, and only tRSE for the R-to-I interval was correlated with height, weight, and body surface area. The high test-retest reliability for CVC in the R-to-I interval provides support for the hypothesis that CVC strength is a subject trait. Across subjects, a peak ∼138 ms prior to I-onset was characteristic of CVC in the R-to-I interval, although individual subjects also had earlier peaks (longer R-to-I intervals). CVC for the R-to-I interval was unrelated to two separate measures of respiratory sinus arrhythmia (RSA), suggesting that these two forms of coupling (CVC and RSA) are independent.


1991 ◽  
Vol 71 (6) ◽  
pp. 2255-2261 ◽  
Author(s):  
A. D. Fryer ◽  
M. Wills-Karp

The effect of antigen challenge on the function of neuronal M2-muscarinic autoreceptors in the lungs was studied in anesthetized guinea pigs. Guinea pigs were injected intraperitoneally with saline (control group) or ovalbumin (10 mg/kg) on days 1, 3, and 5. One group of sensitized animals was challenged on days 20–25 with aerosolized ovalbumin for 5 min/day (challenged group), while another group of the sensitized animals was not challenged (sensitized group). On day 26 the animals were anesthetized, paralyzed, tracheostomized, and artificially ventilated. Pulmonary inflation pressure (Ppi), tidal volume, blood pressure, and heart rate were recorded. Both vagus nerves were cut, and electrical stimulation of the distal portions caused bronchoconstriction (measured as an increase in Ppi) and bradycardia. In the control group, pilocarpine (1–100 micrograms/kg iv) attenuated vagally induced bronchoconstriction by stimulating inhibitory M2-muscarinic receptors on parasympathetic nerves in the lungs. Conversely, blockade of these receptors with the antagonist gallamine (0.1–10 mg/kg iv) produced a marked potentiation of vagally induced bronchoconstriction. These results confirm previous findings. In the challenged guinea pigs, pilocarpine did not inhibit vagally induced bronchoconstriction. Furthermore, gallamine did not potentiate vagally induced bronchoconstriction to the same degree as in the controls. In the group of animals that was sensitized but not challenged, the potentiation of vagally induced bronchoconstriction by gallamine was identical to the controls. There was no increase in baseline Ppi in the sensitized or challenged animals compared with the controls.(ABSTRACT TRUNCATED AT 250 WORDS)


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