Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been hypothesized that naloxone may alter the ventilation-perfusion relationship in patients with chronic obstructive pulmonary disease (COPD) with associated respiratory failure, through the release of hypoxic pulmonary vasoconstriction. To investigate the effects of naloxone on gas exchange, seven clinically stable patients with severe COPD (type B) (forced expiratory volume in one second/forced vital capacity (FEV1/FVC) 38.3 +/- 4.0%) with hypoxaemia and hypercapnia (PaO2 7.6 +/- 0.4 kPa; PaCO2 6.4 +/- 0.3; pH 7.37 +/- 0.02), aged 59.0 +/- 4.6 yr, were studied. Breathing patterns, haemodynamic and conventional and inert gas exchange measurements were made while breathing room air before, during and 60 min after i.v. naloxone infusion. Naloxone and catecholamine plasma levels were also determined. In three subjects (protocol A), measurements were made using increasing concentrations of naloxone (cumulative dose: 54 mg), while the remaining four patients were studied (protocol B) at a fixed concentration of naloxone (cumulative dose: 38 mg). Despite high levels of naloxone (up to 150 ng.ml-1), no significant differences from baseline were observed in any of the measurements, during or after infusion. It is concluded that i.v. naloxone given as described has no effects on pulmonary gas exchange in clinically stable COPD patients with chronic respiratory failure.
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PMID:Gas exchange response to naloxone in chronic obstructive pulmonary disease with hypercapnic respiratory failure. 311 49

To assess the effects of endogenous opiates on respiratory muscle responses to CO2, naloxone was administered intravenously to paralyzed, vagotomized and artificially ventilated cats anesthetized with alpha-chloralose. Neural activity was recorded from the phrenic, hypoglossal (HG), glossopharyngeal (GP) and recurrent laryngeal (RL) nerves. Before naloxone, phasic activity began first in the phrenic at a PETCO2 of 30.0 +/- 1.8 Torr, followed by the RL at a PETCO2 of 33.5 +/- 1.7 Torr, the HG at a PETCO2 of 39.9 +/- 2.1 Torr and the GP at a PETCO2 of 42.5 +/- 2.2 Torr during CO2 rebreathing. Naloxone had no significant effect on the apneic threshold of any of the nerves studied. Naloxone did, however, increase respiratory frequency (P less than 0.01) mainly by causing a significant (P less than 0.01) shortening of TE as it had no significant effect on TI. Naloxone also significantly increased the rate at which peak nerve activity increased with CO2 in the HG (P less than 0.01) and the GP (P less than 0.01) nerves, but not in the phrenic and RL nerves. Instead, the maximum activity produced by hypercapnia and the PETCO2 level at which maximum activity occurred in the phrenic, but not the RL, increased after naloxone. The result of these effects was that naloxone extended the range over which the HG and GP behaved proportionally with the phrenic, but it did not change the curvilinear nature of these relationships.
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PMID:Naloxone enhances the response to hypercapnia of spinal and cranial respiratory nerves. 322 62

Naloxone and related opioid antagonists have been shown to have therapeutic utility in a variety of conditions. The effects of opioid antagonists in either physiological or pathological processes are most clearly seen when there is excessive occupancy of opioid receptors, as in opiate overdose. Opioid antagonists are also able to reverse several types of cardiovascular shock, conditions in which endogenous opioids appear to be mobilised, resulting in increased opioid receptor occupation. There are also more controversial circumstances in which excessive occupation of opioid receptors may assume pathological significance, such as hypercapnia. Opioid antagonists could be useful in such a situation by re-sensitising the respiratory centres to carbon dioxide. There is some evidence that opioid antagonists may benefit some schizophrenic and manic-depressive patients, suggesting that an endogenous opioid ligand might cause disturbances in mental functioning. The diversity and complexity of opioid mechanisms in the central nervous system suggest that more specific opioid antagonists could be more selective in altering physiological or pathological functioning.
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PMID:New and experimental therapeutic roles for naloxone and related opioid antagonists. 631 7

Central cardiovascular and respiratory effects of dermorphin were studied in conscious rats. Intracerebroventricular administration (0.1 or 1 nM) of dermorphin increased the systolic and diastolic blood pressure whereas a high dose (50 nM) decreased blood pressure. Dermorphin at 1 nM increased respiratory rate but caused hypoxia, acidosis and hypercapnia; at 50 nM, respiratory rate was suppressed. Both of these doses produced catalepsy. Stimulation of the sympathoadrenomedullary axis at the pressor period elicited by 1 nM dermorphin was evident by high circulating levels of epinephrine and norepinephrine. N-methyl-atropine reversed the severe bradycardia induced by dermorphin and completely prevented this phenomenon if given as pretreatment. Neither blood pressure nor respiratory depression was altered by the muscarinic blocker. Naloxone (1 mg/kg) reversed the respiratory, cardiovascular and sympathetic effects of dermorphin as well as the catalepsy. These data show that dermorphin has central autonomic effects which are naloxone reversible and mediated by both sympathetic and parasympathetic pathways.
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PMID:Central autonomic effects of dermorphin in conscious rats. 640 44

Ventilatory responses (tidal volume, respiratory frequency, and minute ventilation) to steady-state hypoxia and steady-state hypercapnia were measured plethysmographically in awake unrestrained adult rats, before and after subcutaneous injection of placebo (saline) naloxone in doses up to 5.0 mg/kg. Naloxone did not alter the ventilatory responses to hypoxia or hypercapnia.
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PMID:Naloxone does not affect ventilatory responses to hypoxia and hypercapnia in rats. 642 79

Two female patients revived from fulminant attacks of asthma are described. Ventilatory responses to asphyxia in these patients were 0.70 +/- 0.10 l min-1 % SaO2-1 and 0.64 +/- 0.21 l min-1 % SaO2-1 (mean +/- SEM), respectively. These values were significantly less than the responses of seven normal female subjects (1.54 +/- 0.11 l min-1 % SaO2-1 mean +/- SEM; p less than 0.01). Ventilatory responses to hypercapnia of the two patients were in the low normal range. Dopamine-receptor blockade with prochlorperazine significantly increased the ventilatory response to asphyxia in normal subjects (p less than 0.05 or less for each subject) but did not alter the depressed responses in the asthmatic patients. In one patient, naloxone in a dose of 400 micrograms reversed the decreased ventilatory responsiveness; the response to asphyxia was increased from 0.72 l min-1 % SaO-1 to 1.80 l min-1 % SaO2-1 (p less than 0.01) and the response to hypercapnia was increased from 0.90 l min-1 mmHg-1 to 4.80 l min-1 mmHg-1 (p less than 0.01). Naloxone had no effect in the second asthmatic patient nor in five normal subjects. Defective chemoreceptor responses to chemical stimuli may play a role in sudden death from asthma; endogenous opioids may mediate this disorder of ventilatory control.
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PMID:Ventilatory control in two asthmatics resuscitated from respiratory arrest. 659 13

The respiratory depressant effects of ethanol and their potential reversibility by naloxone were studied in 10 normal subjects. Ventilatory and mouth occlusion pressure (P0.1) responses to hypercapnia and hypoxia without and with an inspiratory resistive load (13 cmH2O X 1(-1) X S) were measured. The resistive load detected with 50% probability (delta R50) and the exponent (n) in Stevens' psychophysical law for magnitude estimation of resistive loads were studied using standard psychophysical techniques. Each of these studies was performed before ethanol ingestion, after ethanol ingestion (1.5 ml/kg, by mouth), and then again after naloxone (0.8 mg iv). Ethanol increased delta R50 (P less than 0.05) and decreased n (P less than 0.05). Naloxone caused no further change in these parameters. The load compensation (Lc), defined as the ratio of loaded to unloaded response slopes, was not significantly changed after ethanol and naloxone. No correlation was found between the Lc and delta R50 or n. The ventilatory and P0.1 responses to hypercapnia and hypoxia with and without inspiratory resistive loading decreased after ethanol (P less than 0.05, hypercapnia; NS, hypoxia). After naloxone the hypercapnic ventilatory responses increased (P less than 0.05). This suggests that the respiratory depressant effects of ethanol may be mediated via endorphins.
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PMID:Effect of ethanol and naloxone on control of ventilation and load perception. 662 28

To investigate the role of endorphins in central respiratory control, the effect of naloxone, a specific opiate antagonist, on resting ventilation and ventilatory control was investigated in a randomised double-blind, placebo-controlled study of normal subjects and patients with chronic airways obstruction and mild hypercapnia due to longstanding chronic bronchitis. In 13 normal subjects the ventilatory response to hypercapnia increased after an intravenous injection of naloxone (0.1 mg/kg), ventilation (VE) at a PCO2 of 8.5 kPa increasing from 55.6 +/- SEM 6.2 to 75.9 +/- 8.21 min-1 (p less than 0.001) and the delta VE/delta PCO2 slope increasing from 28.6 +/- 4.4 to 34.2 +/- 4.21 min-1 kPa-1 (p less than 0.05). There was no significant change after placebo (saline) injection. Naloxone had no effect on resting ventilation or on the ventilatory response to hypoxia in normal subjects. In all six patients naloxone significantly (p less than 0.02) increased mouth occlusion pressure (P 0.1) responses to hypercapnia. Although there was no change in resting respiratory frequency or tidal volume patients showed a significant (p less than 0.01) decrease in inspiratory timing (Ti/Ttot) and increase in mean inspiratory flow (VT/Ti) after naloxone. These results indicate that endorphins have a modulatory role in the central respiratory response to hypercapnia in both normal subjects and patients with airways obstruction. In addition, they have an inhibitory effect on the control of tidal breathing in patients with chronic bronchitis.
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PMID:Endogenous opiates and the control of breathing in normal subjects and patients with chronic airflow obstruction. 716 1

Poststimulatory depression in respiratory activity induced by superior laryngeal nerve (SLN) stimulation was quantitatively investigated in 20 adult cats. The role played in this phenomenon by endogenous opioids was studied using the opiate antagonist naloxone. The effects of hypercapnia on the same phenomenon were also investigated for comparison. Experiments were performed on cats anesthetized with pentobarbitone or alpha-chloralose, vagotomized, paralyzed, and artificially ventilated with 100% O2. Some animals were also carotid sinus denervated. Respiratory output was monitored as integrated phrenic nerve activity. SLN stimulation produced apnea, which outlasted the stimulation period; when respiration resumed, it was markedly depressed as revealed mainly by a decrease in phrenic minute output, respiratory frequency, and rate of rise of inspiratory activity. Phrenic output recovered gradually to control levels following an exponential time course. These effects varied as a function of the duration of SLN stimulation. Naloxone administration (0.8 mg/kg iv) significantly reduced the duration of poststimulatory apnea and attenuated the depression of phrenic minute output of the first recovery breath as a result of changes in peak phrenic activity; it also accelerated the time course of recovery. Hypercapnia did not affect the duration of poststimulatory apnea, but attenuated the initial poststimulatory depression because of changes in respiratory frequency; the rate of recovery was reduced. The results provide characterization of poststimulatory respiratory depression of laryngeal origin in the adult cat and suggest a role of endogenous opioids in its genesis or modulation.
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PMID:Naloxone attenuates poststimulatory respiratory depression of laryngeal origin in the adult cat. 763 83

Acute resistive loading of the airway has been shown to activate the endogenous opioid system, with subsequent depression of ventilation. The present investigation was designed to assess the effect of chronic airway loading on ventilation and CO2 sensitivity, and to determine whether the endogenous opioid system contributes to long-term modulation of ventilatory control in this setting. A flow-resistive ventilatory load was imposed in 2-mo-old rats by surgical implantation of a circumferential tracheal band that approximately tripled tracheal resistance. Respiration and CO2 sensitivity were serially and noninvasively assessed by barometric plethysmography over a period of 21 wk. Ventilatory output was assessed as minute inspiratory effort, which was defined as the product of plethysmograph signal amplitude, inspiratory time, and respiratory rate (RR). CO2 sensitivity was calculated as the percent change in minute inspiratory effort from room air to CO2 exposure. The effect of naloxone administration on these parameters was also determine. Arterial blood gases demonstrated hypercapnia with maintenance of normoxia in loaded rats; these findings persisted for the duration of the study. Two days after surgery, rats with tracheal obstruction demonstrated a lower RR than controls during room air breathing and during CO2 stimulation. CO2 sensitivity was significantly depressed in obstructed animals at this time. Escape from suppression of RR and CO2 sensitivity was evident by 14 to 21 d after obstruction; however, suppression of these parameters reappeared and was maintained from 56 to 147 d after obstruction. Naloxone augmented minute inspiratory effort during CO2 stimulation at 2 d after obstruction but not thereafter; naloxone had no effect in control rats. These data indicate that chronic airway loading suppresses RR and CO2 sensitivity in a triphasic manner. The early suppression is partially reversible by naloxone; late-appearing suppression is unaffected by naloxone and is presumably mediated by mechanisms that do not involve endogenous opioids.
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PMID:Effect of chronic resistive loading on ventilatory control in a rat model. 763 24


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