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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recorded ventilation and genioglossal electromyographic activity in 12 awake, normal subjects before and after they drank 1 ml of ethyl alcohol per kg of body weight. Measurements were made during quiet room air breathing and during hypercapnic rebreathing. Alcohol did not alter minute ventilation, the pattern of breathing, or the ventilatory response to CO2, but it significantly reduced genioglossal activity in both quiet breathing and hypercapnia. The effect was more consistent in male than in female subjects. These results indicate that the neural mechanisms underlying the respiratory activity of the genioglossus are more susceptible to depression by alcohol than those serving the muscles of the ventilatory pump. This susceptibility may be important in the exacerbation by alcohol of obstructive apnea during sleep.
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PMID:Selective reduction of genioglossal muscle activity by alcohol in normal human subjects. 642 Dec 10

We studied the effects of systemically administered ethyl alcohol on the respiratory motor activity of the phrenic, hypoglossal and recurrent laryngeal nerves in unanesthetized, decerebrate cats. Some of the cats were studied after carotid sinus nerve section. In addition, parallel studies were done in intact, awake cats with chronic electromyographic electrodes in the diaphragm, genioglossus, and posterior cricoarytenoid (PCA) muscles. In decerebrate animals, alcohol induced a significant reduction of hypoglossal and recurrent laryngeal nerve activities at doses that had little or no effect on the phrenic nerve discharge. Similar changes were observed in chemodenervated cats. In awake animals, genioglossal and PCA muscle activities were depressed by alcohol, whereas diaphragm activity showed no consistent change. Alcohol caused a significant increase in respiratory frequency in awake cats and reduced the responses of genioglossal and PCA muscle activities to hypercapnia and normocapnic hypoxia. We conclude that alcohol induces a selective reduction in upper airway respiratory motor activity by an action that does not require intact suprapontile structures, vagal afferents, or peripheral chemoreceptors. This reduction may contribute to the alcohol-induced exacerbation of obstructive sleep apnea.
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PMID:Selective depression by ethanol of upper airway respiratory motor activity in cats. 646 68

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

Upon admission, 17 of 223 (8%) consecutive patients with severe head injury exhibited a flaccid, wholly unresponsive motor examination. In this study alcoholic intoxication neither caused depressed motor responsiveness in head-injured patients with high serum ethanol levels nor accounted for the motor examination in those exhibiting the flaccid state. Flaccidity was attributed principally to impaired ventilation in 4 patients, a major intracranial mass in 12, and a spinal cord injury in 1. Compared to the larger group of head-injured patients, the flaccid patients had a significantly greater incidence of hypercapnia (P less than 0.001), acidosis (P less than 0.01), and both elevated and uncontrollable intracranial pressure (ICP) (P less than 0.001). These findings and the high mortality rate (76%) in this study suggest that the magnitude of respiratory complications and the severity of mechanical brain injury are greater in flaccid patients. The flaccid patients undergoing surgical decompression for major intracranial mass lesions (11 cases) have all died and, although still small in number, this group may represent an important subset with a poor prognosis. Nonetheless, a protocol that encourages rapid radiological and electrophysiological assessment and vigorous surgical and ICP management until the probable cause of flaccidity is identified and treated has benefit. The flaccid state was reversed and a good recovery was attained after the restoration of blood pressure and/or ventilation in 2 patients who appeared to have sustained a very grave head injury. In another patient, absent somatosensory evoked potentials greatly facilitated the diagnosis of a spinal subdural hematoma. This program of prompt diagnosis and intense therapy did not result in a protracted course or undue numbers of severely brain-damaged survivors.
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PMID:Flaccidity after head injury: diagnosis, management, and outcome. 730 Oct 64

It has been observed that traumatic brain injury (TBI) increases the susceptibility of the brain to subsequent hypoxia, and prolonged apnea occurs in ethanol (EtOH)-treated animals following brain injury. This investigation tests the hypothesis that EtOH suppresses ventilation and hypercapnic respiratory drive following TBI. Immature pigs were anesthetized with halothane and received a 2 to 3 atm fluid-percussion brain injury. Respiratory parameters, including tidal volume, frequency, ventilation (VE), and arterial blood gases were measured on 100% O2 and on 5% to 6% inspired CO2 in O2 prior to and at 10, 60, 120, and 180 minutes after TBI. Hypercapnic response sensitivity (S) was measured as the change in VE per mm Hg increase in PaCO2. Intracranial pressure, mean arterial blood pressure, heart rate, brain temperature, glucose, and EtOH levels were also monitored. Three groups were studied: the first group of six received EtOH (3.5 gm/kg, intragastrically) without brain injury; the second group of six received TBI without EtOH; the third group of eight received EtOH and TBI. Ethanol levels were 121 +/- 13 (standard error of the mean) mg/dl in the EtOH/TBI group (136 +/- 25 in the EtOH group) at the time of injury, and 175 +/- 12 mg/dl in the EtOH/TBI group (200 +/- 20 mg/dl in the EtOH group) at 120 minutes after injury. The EtOH/TBI animals had significantly lower VE and S, and higher PaCO2 following brain injury (p < 0.05, repeated-measures analysis of variance). No significant differences were identified between groups for pH, PaCO2, intracranial pressure, heart rate, brain temperature, or glucose levels. Ethanol intoxication leads to significant impairment of respiratory control following traumatic brain injury and may contribute to brain injury in intoxicated trauma victims.
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PMID:Effects of ethanol on respiratory function in traumatic brain injury. 771 8

We have previously reported that bedtime ethanol (2.0 ml/kg of 100 proof vodka) increases upper airway closing pressure in males who habitually snored but were otherwise healthy. We also observed that some of these snorers developed obstructive apneas. To explore this phenomenon in more detail, we measured the inspiratory resistance (RI) and respiratory drive after bedtime ethanol in 10 nonobese men (ages 23 to 33) with no history of snoring. Subjects went to bed wearing a tightly fitting valved mask over the nose and mouth that allowed measurement of inspiratory and expiratory flow, pressure in the mask, and endtidal CO2. We measured RI by calculating the pressure difference between the mouth and a balloon positioned in the midesophagus. Respiratory drive was quantified by the inspiratory occlusion pressure (P0.1), the ventilatory response to hyperoxic hypercapnia (delta VE/delta PETCO2), and the ventilatory response to isocapnic hypoxia (delta VE/delta SaO2). Measurements were made during waking and during stage 2 NREM sleep on two nights: (1) when the subjects drank 1.5 ml/kg of 100 proof vodka in orange juice over a 30-min period 15-45 min before lights out and (2) when the orange juice contained less than 0.1 ml of vodka floating on the top. Eight of the nine men in whom we had technically adequate measurements showed a rise in RI during NREM sleep above the waking level on both control and ethanol nights and the sleeping RI was greater on the ethanol than on the control night.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcohol Clin Exp Res 1993 Apr
PMID:Effect of bedtime ethanol on total inspiratory resistance and respiratory drive in normal nonsnoring men. 848 64

We measured inspiratory resistance (R1), inspiratory occlusion pressure (P0.1), and the ventilatory responses to hypercapnia and isocapnic hypoxia during waking and during stage 2 non-rapid eye movement sleep in nine young men who were habitual snorers. They were studied on 2 nights during the 3 hours after receiving a bedtime drink containing either a placebo or 100-proof vodka (1.5 ml/kg) in orange juice. We compared the results with those we reported previously in 10 nonsnoring but otherwise similar men. Waking R1 was the same in nonsnorers and snorers, and it was not affected by ethanol. During sleep on the control night, R1 increased by 70% in nonsnorers and by 280% in snorers. On the ethanol night, the increase from waking to sleeping was more than doubled in both nonsnorers and snorers. P0.1 and the responses to hypercapnia and hypoxia showed no differences between nonsnorers and snorers, therefore the results from the two groups were pooled. Minute ventilation and the hypercapnic response decreased from waking to sleeping and P0.1 was more negative during sleep, but there was no significant effect of ethanol. There was a significant correlation between the changes from waking to sleeping in R1 and P0.1 on the ethanol night suggesting that inspiratory effort increased in response to the increased resistance. The response to isocapnic hypoxia showed no effect of either sleep state or drink. Inspiratory time did not change but mean inspiratory flow (VT/T1) was significantly reduced during sleep on both control and ethanol nights. The duty cycle ratio (T1/Ttot) was significantly increased during sleep on the ethanol night. Despite its great effect on inspiratory resistance, especially in snorers, ethanol, in the dose used in our study, does not augment the depression of minute ventilation or of the hypercapnic response that occur normally in stage 2 non-rapid eye movement sleep. After ethanol, our subjects showed the decreased VT/T1 and the increased T1/Ttot that occur normally during sleep in response to an inspiratory resistive load. However, they also showed increased inspiratory effort. The combination of increased inspiratory resistance and greater inspiratory effort would increase the tendency of an unstable upper airway to collapse and could account for the aggravation of obstructive sleep apnea by ethanol.
Alcohol Clin Exp Res 1997 Apr
PMID:Effect of bedtime alcohol on inspiratory resistance and respiratory drive in snoring and nonsnoring men. 911 50

Alcohol intake has been shown to worsen obstructive sleep apnea and increase nocturnal hypoxemia. The mechanisms of this action are unclear. Animal studies suggest that a reduction in chemoreflex sensitivity may be implicated. Using a double-blind, randomized, vehicle-controlled design, we tested the hypothesis that oral alcohol intake depresses chemoreflex sensitivity in humans. We examined the effects of oral alcohol intake (1.0 g/kg body wt) on blood pressure, heart rate, heart rate variability, muscle sympathetic nerve activity, forearm vascular resistance, and minute ventilation in 16 normal male subjects. Peripheral and central chemoreflex sensitivity were measured in response to hypoxia (n = 10) and hypercapnia (n = 6), respectively. Plasma alcohol increased from 0 to 23.2 +/- 1.5 mmol/L (107 +/- 7 mg/dL) at 60 minutes and 20.2 +/- 1 mmol/L (93 +/- 4 mg/dL) at 85 minutes after alcohol intake (P < .0001). Alcohol induced an increase in heart rate from 59 +/- 2 to 66 +/- 2 beats per minute (P < .01) and increased the ratio of low- to high-frequency variability of heart rate (P < .05). Although alcohol increased sympathetic nerve activity by up to 239 +/- 22% of baseline values (P < .01), forearm vascular resistance after alcohol was lower than that after vehicle (P < .05). Blood pressure did not increase compared with the vehicle session. Oxygen saturation during hypoxia after alcohol was 4 +/- 1% lower than it was during hypoxia after vehicle (P < .05) although arterial blood PO2 was unchanged. Alcohol did not affect the cardiovascular, sympathetic, or ventilatory responses to either hypoxia or hypercapnia. Acute increases in plasma alcohol increase heart rate and sympathetic nerve activity; blood pressure is not increased, probably because of vasodilator effects of alcohol. Alcohol does not alter chemoreflex responses to hypoxia or hypercapnia; thus, alterations in chemoreflex sensitivity are unlikely to explain the effects of alcohol on sleep apnea. Alcohol may reduce the affinity of hemoglobin for oxygen.
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PMID:Effects of alcohol on sympathetic activity, hemodynamics, and chemoreflex sensitivity. 918 Jun 29

Previous experimental findings have led to the suggestion that guanosine 3',5'-cyclic monophosphate (cGMP) plays a permissive role in hypercapnic cerebral vasodilation. However, we recently reported that the technique used to reveal a permissive role for cGMP [cGMP repletion in the presence of nitric oxide synthase (NOS) inhibition] created a situation where CO(2) reactivity was normalized but where different mechanisms (i.e., K(+) channels) participated in the response. In the present study, we examined whether that nascent K(+)-channel dependence is related in any way to an increase in the influence of the miconazole-inhibitable cytochrome P-450 epoxygenase pathway. Using intravital microscopy and a closed cranial window system in adult rats, we measured pial arteriolar diameters during normo- and hypercapnia, first in the absence and then in the presence of a neuronal NOS (nNOS) inhibitor [7-nitroindazole (7-NI)]. This was followed by suffusion of a cGMP analog and then cGMP plus miconazole. Separate groups of rats were used to evaluate whether miconazole either alone or in the presence of 8-bromoguanosine 3', 5'-cyclic monophosphate (8-BrcGMP) or its vehicle (0.1% ethanol) had any effect on CO(2) reactivity and whether miconazole affected K(+)-channel opener-induced dilations. Hypercapnic (arterial PCO(2), congruent with65 mmHg) pial arteriolar dilations, as expected, were reduced by 70-80% with 7-NI and restored with cGMP repletion. CO(2) reactivity was again attenuated after miconazole introduction. Miconazole, with and without 8-BrcGMP, and its vehicle had no influence on pial arteriolar CO(2) reactivity in the absence of nNOS inhibition combined with cGMP repletion. Miconazole alone also did not affect vasodilatory responses to K(+)-channel openers. Thus present results suggest that the nascent K(+)-channel dependence of the hypercapnic response found in our earlier study may be related to increased epoxygenase activity. The specific reasons why the pial arteriolar CO(2) reactivity gains a K(+)-channel and epoxygenase dependence only under conditions of nNOS inhibition and cGMP restoration remain to be identified. These findings again call into question the interpretations applied to data collected in studies evaluating potential permissive actions of cGMP or NO.
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PMID:Miconazole represses CO(2)-induced pial arteriolar dilation only under selected circumstances. 1051 86

More than one-third of patients diagnosed with head injury are intoxicated with ethanol. Most clinical and animal studies have shown alcohol to have a deleterious impact in the setting of cerebrovascular trauma; however, there are also data showing neuroprotective effects in low ethanol doses. Human studies using imaging modalities suggest that small doses of alcohol produce cerebral vasodilatation and higher doses cerebral vasoconstriction. The aim of this study was to investigate the effect of ethanol intake on dynamic cerebral autoregulation and velocities in the middle cerebral arteries, and compare these changes with the effects of hypercapnia. Dynamic cerebral autoregulation and cerebral blood flow velocities were analysed before and after alcohol intake (1.1 g/kg of body weight) in six adult volunteers. Cerebral blood flow velocities in both middle cerebral arteries were monitored continuously by transcranial Doppler. A value for dynamic cerebral autoregulation was calculated from the rate of increase in middle cerebral artery velocities after a rapid-step decrease in arterial blood pressure. A sudden decrease in blood pressure was achieved by the release of previously inflated large blood pressure cuffs around the subject's thighs. Three volunteers were also tested before alcohol intake with CO(2) challenge (breathing 6% CO(2)) during the autoregulation procedure. Blood alcohol level reached 90 mg/dl approximately 60 min after ethanol ingestion. Cerebral blood velocities increased by 8% from baseline for uncorrected end-tidal (et) CO(2) and by 24% for correction to et CO(2)=40. Dynamic cerebral autoregulation measured as an autoregulation index decreased from 4.3+/-1.3 to 2.9+/-1.1 (p=0.089), which did not reach statistical significance. During hypercapnic conditions, dynamic cerebral autoregulation dropped from 4+/-0.8 to 0.9+/-0.9. In conclusion, mild alcohol intoxication caused cerebral vasodilatation with a subsequent increase in cerebral blood flow of 8-24%. Dynamic cerebral autoregulation was not found to be significantly impaired by ethanol. Hypercapnia almost completely destroys the physiological autoregulatory mechanism. A mild hyper-ventilation to etCO(2)=34-36 may be a compensatory contra-measure for ethanol-induced vasodilatation in the setting of head trauma.
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PMID:Cerebral blood flow and dynamic cerebral autoregulation during ethanol intoxication and hypercapnia. 1263 48


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