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)

The role of adrenal medulla-derived enkephalins in the control of hypercapnic cerebrocortical blood flow (CBF) and oxygen consumption (CMRO2) was investigated in the ketamine anesthetized rat. Three experimental interventions were utilized: inhibition of opioid receptors with naloxone, decrease of adrenal enkephalin production with chronic adrenal medullectomy, and treatment of adrenal demedullated animals with the synthetic enkephalin analog, D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAGO). In intact, untreated animals hypercapnia increased CBF and CMRO2 by approximately 300 and 35%, respectively. Naloxone reduced the hypercapnic increase of CBF, and transformed the hypercapnic increase of CMRO2 into a decrease. The mid-points of the dose-response curves for (1)-naloxone and (d)-naloxone were 10 micrograms/kg and 100 micrograms/kg, respectively. Adrenal demedullation and treatment with (1)-naloxone (0.2 mg/kg) decreased the hypercapnic CBF and CMRO2 by approximately 50%. DAGO treatment of adrenal demedullated animals restored the hypercapnic CBF and CMRO2 to values similar to those found in intact animals. These observations suggest that opioid peptides (most likely adrenal medulla-derived enkephalins) play a significant role in the regulation of CMRO2 and CBF during moderate hypercapnia.
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PMID:Significance of an opiate mechanism in the adjustment of cerebrocortical oxygen consumption and blood flow during hypercapnic stress. 150 67

To clarify whether endogenous opioids play modulatory roles in control of breathing and have any specific effects on the intensity of dyspnea, healthy volunteers were examined for two protocols of ventilatory response tests. 1) The ventilatory response to hypercapnic progressive hypoxia and the withdrawal response to assess peripheral chemoreceptor activity were compared before and after intravenous infusion of 3 mg naloxone in 21 healthy adults. The average ventilatory response increased significantly after naloxone infusion (p less than 0.05), whereas there were no significant changes between two tests with normal saline in the control study (n = 7). Because there was considerable interindividual variation in the response to naloxone administration, "high responders" (n = 8) who showed larger increases with naloxone than the upper limit of the 95% confidence interval for the change with the second saline in the control study were selected. They showed greater ventilatory responses before naloxone infusion than did the other subjects (p less than 0.01). There was no significant change in the withdrawal response before and after naloxone infusion, even in such high responders. 2) The ventilatory and peak mouth pressure responses to hypoxic progressive hypercapnia with inspiratory flow-resistive loading were measured after the intravenous infusion of 3 mg naloxone or saline in 11 male volunteers, while the intensity of dyspnea was simultaneously assessed. Naloxone administration increased the peak mouth pressure response (p less than 0.05) although the increase in ventilatory response did not reach statistical significance. The intensity of dyspnea tended to be greater after naloxone infusion than after saline infusion at end-tidal PCO2 levels of 55 Torr and 60 Torr (p = 0.06 and 0.09, respectively). However, the intensity of dyspnea was quite similar between trials with and without naloxone when compared at equivalent levels of either minute ventilation or peak mouth pressure. These findings suggest that endogenous opioids suppress respiratory outputs under a strong, acute respiratory stress in normal humans. This may be particularly true for those subjects who have greater chemosensitivity. Endogenous opioids appear to act centrally rather than peripherally, but do not have any specific modulatory role on the sensation of dyspnea.
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PMID:[Role of endogenous opioids in respiratory control system and dyspnea sensation in healthy adult humans]. 155 57

Thirty elderly patients undergoing major hip surgery under spinal analgesia were randomly allocated in a double-blind manner into three groups. The aim was to evaluate the influence of intrathecal morphine and postoperative naloxone infusion on the regulation of ventilation. The Bupivacaine Group received spinal analgesia with 20 mg bupivacaine intrathecally. The Morphine Group received spinal analgesia with 20 mg bupivacaine + 0.3 mg morphine intrathecally. The Naloxone Group received spinal analgesia with 20 mg bupivacaine + 0.3 mg morphine intrathecally + postoperative naloxone infusion intravenously (1 microgram/kg/h over 12 h, 0.25 micrograms/kg/h over the next 12 h). Evaluation of resting ventilation and the ventilatory responses to hypercarbia and hypoxaemia was made on three occasions: before surgery, and 8, and 24 h after the intrathecal injection. Intrathecal morphine had no significant effect on ventilatory regulation in elderly patients undergoing major hip surgery performed under bupivacaine spinal analgesia. Postoperative administration of opioids or sedatives after intrathecal morphine as well as postoperative blood loss associated with a fall in blood pressure appeared to increase the risk of developing respiratory depression. Naloxone infusion seemed to reduce the risk of developing respiratory depression. Furthermore, one third of the elderly had a poor response to hypoxaemia before surgery.
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PMID:Influence of intrathecal morphine and naloxone intervention on postoperative ventilatory regulation in elderly patients. 163 66

The widespread, heterogeneous distribution of opiate receptors and their endogenous ligands in the nervous system are reflective of the variety of central and systemic effects seen after opiate administration. Most neurons respond to either systemic or local opiate application with a decrease in firing rate, although increased neuronal activity has also been reported in such regions as the caudate, amygdala, ventral tegmentum, and substantia nigra. While regional metabolic studies have consistently reported neuronal suppression, some portion of this might be secondary to systemic hypercapnia. Using a brief blood flow marker, we recently reported a heterogenous increase in activity in more than half of the brain regions examined. To extend that study, we report herein the results of a dose-response and antagonist challenge experiment. Rats received an acute injection of one of the following: heroin (0.1, 0.3 or 1.0 mg/kg), naloxone (1.0 mg/kg), a cocktail of heroin (0.3 mg/kg) plus naloxone or saline. One min after drug administration, 160 muCi/kg [1-14C] octanoate, a marker for cerebral blood flow, was delivered IV. Rats were sacrificed two min later, brains removed and prepared for autoradiography. Of the fifty-eight areas analyzed, heroin caused an increase in blood flow in the caudate, claustrocortex, laterodorsal thalamus and dentate gyrus. Decreases were found for the bed nucleus of the stria terminalis, preoptic area, basolateral nucleus of the amygdala, dorsomedial and paraventricular hypothalamus, entorhinal and cingulate cortices and dorsal raphe. Naloxone resulted in significant increases in the olfactory tubercle and paraventricular nucleus while decreases were seen in the cingulate and basolateral amygdala.
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PMID:Effects of heroin and naloxone on cerebral blood flow in the conscious rat. 180 37

Previous studies have shown that systemic administration of the opiate antagonist naloxone potentiates the ventilatory response to inspired carbon dioxide. The present study was designed to localize the site of action of naloxone for increasing the respiratory chemosensitivity to inhaled carbon dioxide (CO2) in cats. Naloxone applied topically to the caudal chemosensitive area on the ventral medullary surface (VMS) during hypercapnic breathing produced a 75% greater increase in minute ventilation than hypercapnic breathing alone. Furthermore, hypercapnic breathing produced a 200% increase in neuronal activity of VMS chemosensitive cells; this was further increased 120% by naloxone. It is concluded that naloxone increases the sensitivity of neurons in the caudal respiratory chemosensitive area of cats to hypercapnia, and that endogenous opiates may act as modulators at VMS chemosensitive sites during hypercapnic breathing.
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PMID:Naloxone application to the ventrolateral medulla enhances the respiratory response to inspired carbon dioxide. 190 72

Defense of ventilatory homeostasis against recurrent hypercapnia, hypoxia, and acidosis resulting from apnea in obstructive sleep apnea syndrome (OSAS) is dependent on compensatory mechanisms operative between episodes of airway obstruction. This investigation was designed to examine whether endogenous opiate activity modulates the compensatory ventilatory response to apnea in OSAS. Polysomnography and quantitative measurement of tidal volume was performed in 12 patients with moderate to severe OSAS during a morning nap study before and after intravenous administration of 10 mg of naloxone. Apnea index was not significantly altered. There was a small but significant shortening of apneas (postnaloxone apnea duration, 91.2% of prenaloxone; p = 0.002 by ANOVA). Tidal volume of the first postapnea breath and minute ventilation extrapolated from the first two postapnea breaths, but not frequency, increased significantly after naloxone (postnaloxone first breath volume, 112.7% of prenaloxone value [p = 0.03], with a similar increase for minute ventilation, 115.1% [p = 0.007]). The volume of the first postapnea breath was correlated with the duration of the previous apnea, both before (r = 0.59, p = 0.0001) and after naloxone. Despite this, analysis of covariance with apnea duration as the covariate confirmed a significant independent increase in postapnea breath volume after naloxone (p = 0.001). Naloxone also altered sleep architecture, increasing percent time awake during the study period (prenaloxone, 36.3 +/- 15.6%; postnaloxone, 56.7 +/- 22.4%; p = 0.0003) and decreasing total sleep time and percent time in Stage 1. Furthermore, naloxone increased continuity of awake periods (mean length of awake periods increased from 27.0 +/- 8.4 to 66.0 +/- 66.6 s after naloxone, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endogenous opiates modulate the postapnea ventilatory response in the obstructive sleep apnea syndrome. 204 14

The effects of the opiate antagonist naloxone (0.4 mg.kg-1, i.v.) on carotid chemoreceptor and ventilatory responses to graded steady-state levels of hypoxia and hypercapnia were investigated in two groups of cats: chronically normoxic and chronically hypoxic. The cats of the latter group were exposed to PIO2 of about 70 mm Hg at sea level for 3-4 weeks and showed an attenuated response to hypoxia. All cats were tested under alpha-chloralose anesthesia. Naloxone treatment did not increase appreciably carotid chemoreceptor activity or its responses to hypoxia and hypercapnia in either cat group. Naloxone caused a small ventilatory stimulation in the chronically hypoxic cats, so that the attenuated response to hypoxia was not relieved. By contrast, the chemoreflex ventilatory response to hypoxia was stimulated by naloxone in the chronically normoxic cats. The findings that the depressed ventilatory chemoreflexes in the chronically hypoxic cat were not ameliorated by the opiate antagonist indicate that an increased elaboration of endogenous opiates does not underlie ventilatory adaptation to chronic hypoxia.
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PMID:Endogenous opiates and ventilatory acclimatization to chronic hypoxia in the cat. 206 18

The effect of naloxone on fetal breathing and the respiratory sensitivity to CO2 was tested on chronically prepared fetal lambs on days one and four post-surgery. After a control period the fetus was challenged with hypercapnia for 10 min and after another control period 9 mg naloxone was administered to the fetus followed by another CO2 test 15 min later. An index of fetal breathing (Veq), tidal volume (VT) and frequency of breathing (f) was determined from tracheal pressure deflections and from the integrated diaphragmatic EMG, expressed as power of diaphragmatic activity per min. Naloxone consistently caused fetal arousal but the duration was variable. The respiratory response to naloxone was also variable and not statistically different from control. The respiratory sensitivity to CO2 (% delta Veq/Torr delta PaCO2 or % delta Diaph. Power/min/Torr delta PaCO2) was not changed by naloxone on either day. We conclude that endorphins do not have a significant direct role in the fetal respiratory response to CO2 but may be involved in the control of state.
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PMID:Influence of naloxone on fetal breathing and the respiratory response to hypercapnia. 251 53

To assess the role of endogenous opioid peptides in ventilatory control in patients with chronic obstructive lung disease, we measured the ventilatory and mouth occlusion pressure responses to hypercapnia and the compensatory response to an inspiratory resistive load in 11 male patients with COPD before and after intravenous administration of naloxone or placebo on 2 separate days. There were no statistically significant differences between naloxone and placebo administration in any index of ventilatory response to CO2 or resistive loading. When an inspiratory resistive load was added during CO2 rebreathing, minute ventilation at PETCO2 = 50 mm Hg in all 11 patients decreased significantly (p less than 0.05) with placebo and naloxone. In response to the inspiratory resistive load, in eight of the 11 patients mouth occlusion pressure (P0.1) did not increase; these eight subjects were classified as noncompensators. Naloxone did not affect the P0.1 response to inspiratory resistive loading, either in the group as a whole or in the subgroup of eight patients classified as noncompensators. Our study was unable to demonstrate that increased activity of endogenous opioid peptides suppresses the ventilatory response to CO2 or resistive loading in patients with chronic obstructive lung disease.
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PMID:Naloxone does not alter response to hypercapnia or resistive loading in chronic obstructive pulmonary disease. 264 73

To determine whether endogenous opioids influence the fetal breathing response to CO2 we have investigated the effect of the opiate antagonist, naloxone on the incidence, rate, and amplitude of breathing movements during hypercapnia in fetal lambs in utero. In 20 experiments in six pregnant sheep (130-145 days gestation) hypercapnia was induced by giving the ewe 4-6% CO2-18% O2 in N2 to breathe for 60 min. After 30 min of hypercapnia either naloxone (13 experiments) or saline (7 experiments) was infused intravenously for the remaining 30 min. During hypercapnia breath amplitude increased from 5.8 +/- 0.5 to 9.1 +/- 1.2 mmHg (P less than 0.001), and infusion of naloxone was associated with a further significant increase to 15.7 +/- 1.2 mmHg (P less than 0.001). Naloxone had no effect on the incidence or rate of breathing movements during hypercapnia. After hypercapnia there was a significant decrease in the incidence of fetal breathing movements in the naloxone group (14.7 +/- 3.2%). Infusion of saline during hypercapnia had no effect on incidence, rate, or amplitude of fetal breathing movements. These results suggest that endogenous opioids act to suppress or limit breath amplitude during hypercapnia but do not affect rate or incidence of breathing movements.
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PMID:Effects of naloxone on breathing movements during hypercapnia in the fetal lamb. 310 97


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