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)

Previously, our laboratory has demonstrated inhibition of mitochondrial state 3 (ADP-dependent) respiration 5 min after resuscitation from an asphyxial insult in lambs less than 3 days of age. Older lambs were resistant to this transient mitochondrial dysfunction. This study was designed to examine if age-related differences in baseline state 3 mitochondrial respiration, electron transport chain activity, or susceptibility to oxygen free radical-mediated lipid peroxidation were related to the previously observed differences in postasphyxial mitochondrial respiration. Mitochondrial respiration was measured in 24 nonasphyxiated control lambs aged 1-10 days using four different substrates. Electron transport chain activity was assessed in 15 of these lambs, and lipid peroxidation measured as conjugated diene production was measured in 11 of these lambs. These lambs were all ventilated to maintain normal blood gases for a time period equal to the length of the hypoxic insult in asphyxiated lambs (see below), after which samples of brain were removed for isolation of mitochondria. A second group of 11 lambs (seven < or = 3 days of age and four > 3 days of age) were asphyxiated. The insult was a 75-to-90-min episode of hypoxia and hypercarbia that resulted in bradycardia and systemic hypotension over the final 15 min of the insult. At the end of asphyxia, the lambs were resuscitated and returned to control ventilator settings. Samples of brain were removed 5 min after resuscitation. Postasphyxia electron transport chain activity and lipid peroxidation were measured. All measurements described above were done in both nonsynaptic (primarily glial in origin) and synaptic mitochondria. State 3 mitochondrial respiration varied significantly with age, decreasing by an average of 41.2% +/- 11.1% (mean +/- SEM) from Day 2 to Day 5-6 and then increasing back to levels similar to Day 2 by Day 8-10 in nonsynaptic mitochondria. State 3 respiration in synaptic mitochondria decreased 60.6% +/- 5.2% from Day 2 to Day 5-6 before returning to levels similar to Day 2 by Day 8-10. Resting (nonADP-dependent) state 4 respiration demonstrated similar developmental patterns. Electron transport chain activities did not vary with age in the nonasphyxiated control animals. In addition, an asphyxial insult did not diminish electron transport chain activities in either lambs < or = 3 days old or those > 3 days of age.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Developmental changes in newborn lamb brain mitochondrial activity and postasphyxial lipid peroxidation. 777 Apr 68

To investigate the effects of digitalis on chemoreflexes in humans, we measured muscle sympathetic nerve activity (microneurography), minute ventilation, oxygen saturation, end-tidal carbon dioxide, mean arterial pressure, heart rate, and central venous pressure during stimulation of peripheral chemoreceptors with hypoxia, during stimulation of central chemoreceptors with hypercapnia, and during a cold pressor test before and after digitalis and placebo in 10 healthy volunteers on two different days (randomized, double-blind, cross-over design). Digitalis did not affect baseline measurements significantly. Despite similar changes in oxygen saturation and end-tidal carbon dioxide during hypoxia and hypercapnia with both placebo and digitalis, digitalis significantly potentiated overall ventilatory responses to hypoxia (+67 +/- 12% before versus +98 +/- 3% after digitalis; mean +/- SEM; P < .01) but did not affect the response to hypercapnia. Sympathetic nerve activity increased by 25 +/- 9% during hypoxia before digitalis and 30 +/- 10% during hypoxia after digitalis (P = NS) and increased by 38 +/- 18% during hypercapnia before digitalis and 26 +/- 11% during hypercapnia after digitalis (P = NS). Digitalis did not significantly change responses to the cold pressor test. Placebo had no effect on ventilatory and sympathetic nerve activity responses. We conclude that digitalis selectively augments ventilatory responses to peripheral chemoreceptor stimulation by hypoxia.
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PMID:Differential effects of digitalis on chemoreflex responses in humans. 812 54

In a double-blind, randomized study, we have compared the effects of i.v. ketoprofen 200 mg followed by 12.5 mg h-1 over 13 h, with those of extradural morphine 4 mg in 32 patients after hip and knee arthroplasty. A visual analogue scale was used to score pain before analgesic administration (first complaint after operation), 1 h after and every 2 h subsequently. Pain reduction 1 h after the start of analgesia was mean 44% (SEM 17%) in the extradural morphine group and 54% (9%) in the ketoprofen group (ns). There were no significant differences between groups in pain scores, pain reduction and additional analgesia requirement (i.v. paracetamol). Naloxone 5 micrograms kg-1 h-1 was required for hypercapnia exceeding 6.0 kPa in three patients in the extradural morphine group (vs none in the ketoprofen group; ns). There were no differences between groups in side effects, except for urinary retention, which was more frequent in the extradural morphine group (P < 0.05). As there were few differences between i.v. ketoprofen and extradural morphine, we conclude that ketoprofen may be an efficient alternative to extradural morphine after hip and knee arthroplasty.
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PMID:Ketoprofen for pain after hip and knee arthroplasty. 815 35

We have investigated the effects of acidic stimuli upon [Ca2+]i in isolated carotid body type I cells from the neonatal rat using indo-1 (AM-loaded). Under normocapnic, non-hypoxic conditions (23 mM HCO3-, 5% CO2 in air, pHo = 7.4), the mean [Ca2+]i for single cells was 102 +/- 5.0 nM (SEM, n = 55) with 58% of cells showing sporadic [Ca2+]i fluctuations. A hypercapnic acidosis (increase in CO2 to 10%-20% at constant HCO3-, pHo 7.15-6.85), an isohydric hypercapnia (increase in CO2 to 10% at constant pHo = 7.4) and an isocapnic acidosis (pHo = 7.0, constant CO2) all increased [Ca2+]i in single cells and cell clusters. The averaged [Ca2+]i response to both hypercapnic acidosis and isohydric hypercapnia displayed a rapid rise followed by a secondary decline. The averaged [Ca2+]i response to isocapnic acidosis displayed a slower rise and little secondary decline. The rise of [Ca2+]i in response to all the above stimuli can be attributed to no single factor other than to a fall of pHi. The hypercapnia-induced rise of [Ca2+]i was almost completely abolished in Ca(2+)-free solution, suggesting a role for Ca2+ influx in triggering and/or sustaining the [Ca2+]i response. These results are consistent with a role for type I cell [Ca2+]i in mediating pH/PCO2 chemoreception.
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PMID:Effects of acidic stimuli on intracellular calcium in isolated type I cells of the neonatal rat carotid body. 827 80

Although nasal continuous positive airway pressure (CPAP) is effective in the treatment of most patients with obstructive sleep apnea (OSA), there is a small group of such patients in whom rapid eye movement (REM) hypoventilation and CO2 retention persist despite the use of CPAP and supplemental oxygen. In this report we describe our experience with nocturnal nasal ventilation (nocturnal nasal positive pressure ventilation [NIPPV] in such patients and its effectiveness in reversing daytime hypercapnia. Thirteen patients, aged 28 to 69 years, with severe OSA confirmed on polysomnography, failed to respond to initial CPAP therapy. All were grossly obese (body mass index [BMI] > 35 kg.ml-1) and hypercapnic (mean PaCO2, 62 mm Hg). Nocturnal nasal ventilation was commenced using a volume-cycled ventilator, which was well tolerated in all patients. After 7 to 18 days of NIPPV, significant improvements in daytime arterial blood gas values were achieved, with a rise in arterial oxygen tension from 50 +/- 2.6 (SEM) to 66 +/- 3 mm Hg (p < 0.001) and a fall in CO2 from 62 +/- 2.5 to 46 +/- 1 mm Hg (p < 0.0001). Nine of the 13 patients were able to be established on a regimen of nasal CPAP after this period, while 3 patients required a longer period (up to 3 months) before adequate nocturnal ventilation could be maintained. In one patient, the improvements in ventilatory drive achieved with NIPPV could not be maintained on CPAP, and she was transferred on to NIPPV long term. These results indicate that effective nasal ventilation leads to an overall improvement in spontaneous ventilation and blood gas values both awake and asleep. We believe this improvement is the result of improved central ventilatory drive. Short-term NIPPV provides lasting benefits allowing the majority of such patients to resume CPAP therapy. Short-term intervention with this therapy should be considered as an interim measure in patients with severe hypercapnic OSA who fail to respond to initial CPAP therapy.
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PMID:Effects of short-term NIPPV in the treatment of patients with severe obstructive sleep apnea and hypercapnia. 771 May 19

Since activity of the genioglossus muscle plays a primary role in maintaining upper airway patency during sleep, its strength and endurance characteristics are of potential importance. The purpose of this study was 2-fold. First, to define the strength and endurance characteristics of the normal human genioglossus. Second, we hypothesized that because the genioglossus has a high proportion of fast glycolytic muscle fibers, brief periods of increased activity would make it more susceptible to fatigue. In five normal male subjects strength of the tongue was evaluated by measuring maximal anterior force using a transducer (Fmax). In each subject tongue endurance was then tested at 100%, 80%, and 50% Fmax. To test the effect of a short-term increase in genioglossal activity on its endurance, an inspiratory flow-resistive load with mild hypercapnia was presented to the upper airway for 10 min, after which genioglossal endurance at 80% Fmax was repeated. On a separate day the effect of inspiratory loading plus hypercapnia on thoracic inspiratory muscle endurance was also tested. Our results showed that mean Fmax was 1,267 +/- 125 (SEM) g. Endurance time (Tlim) decreased progressively during 50%, 80% and 100% Fmax trials. Short-term activation of the genioglossus caused a reduction in Tlim at 80% Fmax to 51.4 +/- 4.8% of its value before loading (p < 0.05). Tlim for the inspiratory muscles, however, was unaffected. We conclude that, like other skeletal muscles, genioglossal endurance is reduced as the force of contraction increases. In addition, genioglossal endurance is significantly reduced by short-term activation insufficient to fatigue the thoracic inspiratory muscles.
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PMID:Strength and endurance characteristics of the normal human genioglossus. 831 95

Upper airway dilating muscle activity increases during apneic episodes in patients with obstructive sleep apnea (OSA). To elucidate the relative contribution of chemical and nonchemical stimuli to augmentation of the upper airway dilating muscle, we measured the response of genioglossus muscle (GG) and inspiratory intercostal muscle (IIM) activities to obstructive apnea during non-REM sleep and compared them with the response to progressive hypoxia and hypercapnia during awake periods in seven male patients with OSA. GG EMG was measured with a wire electrode inserted percutaneously, and IIM EMG was measured with surface electrodes placed in the second intercostal space parasternally. Responses to hypoxia and to hypercapnia were assessed by rebreathing methods in the supine position while awake. Following these measurements, a sleep study was conducted with the EMG electrodes placed in the same locations. The relationship between GG and IIM activities during the cycle of apnea and postapneic ventilation in non-REM sleep was quasi-linear, and the slope of the regression line was significantly greater than those during progressive hypoxia and progressive hypercapnia. The amplitude of GG activity at 70% of maximum IIM activities in the hypoxic test was 140 +/- 20% (mean +/- SEM) during non-REM sleep, which was also significantly greater than that during hypoxia (51 +/- 10%) and that during hypercapnia (59 +/- 15%). These results suggest that nonchemical factors contribute considerably to augmentation of GG activity during obstructive apneic episodes. The nonchemical stimuli may arise from mechanoreceptors activated by upper airway obstruction and behavioral factors associated with change in sleep states.
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PMID:Role of chemical drive in recruiting upper airway and inspiratory intercostal muscles in patients with obstructive sleep apnea. 842 Apr 16

We examined the effects of aging on the metabolic respiratory control system by measuring changes with time in steady-state minute volume of ventilation (VI), alveolar carbon dioxide pressure (PACO2), and ventilatory and arousal responses to hypercapnia and hypoxia during slow-wave sleep (SWS). Studies were performed longitudinally in six healthy dogs over a span of 3 to 7 yr, corresponding biologically to 12 to 24 human yr. In each of the dogs aging was associated with a decrease in steady state VI during SWS, from 6.53 +/- 1.08 (mean +/- SEM) to 5.56 +/- 0.90 L/min (p < 0.01), and with an increase in PACO2 from 36.2 +/- 1.0 to 38.5 +/- 1.1 mm Hg (p < 0.01). However, ventilatory and arousal responses to hyperoxic hypercapnia (four dogs) remained unchanged. In contrast there was a decrement in the response of VI to isocapnic hypoxia during SWS (five dogs), from 1.22 +/- 0.12 to 0.70 +/- 0.07 L/min/% fall in arterial O2 saturation (SaO2) (p < 0.02), and a decrease in arousal SaO2, from 83.3 +/- 3.2 to 73.5 +/- 2.3 percent (p < 0.001). The findings indicate that aging is accompanied by impairment of ventilatory and arousal responses to hypoxia during SWS, and point to a specific effect of aging on the carotid-body chemoreceptors, as opposed to the brainstem respiratory controller or the ventilatory pump.
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PMID:Effect of aging on metabolic respiratory control in sleeping dogs. 850 64

Reduced tolerance to high altitude may be associated with a low ventilatory and an increased pulmonary vascular response to hypoxia. We therefore, examined whether individuals susceptible to acute mountain sickness (AMS) or high altitude pulmonary oedema (HAPE) could be identified by noninvasive measurements of these parameters at low altitude. Ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) at rest and during exercise, as well as hypoxic pulmonary vascular response (HPVR) at rest, were examined in 30 mountaineers whose susceptibility was known from previous identical exposures to high altitude. Isocapnic HVR expressed as difference in minute ventilation related to difference in arterial oxygen saturation (delta V'E/ delta Sa,O2) (L.min-1/%) was significantly lower in subjects susceptible to HAPE (mean +/- SEM 0.8 +/- 0.1; n = 10) compared to nonsusceptible controls (1.5 +/- 0.2; n = 10), but was not significantly different from subjects susceptible to AMS (1.2 +/- 0.2; n = 10). Hypercapnic ventilatory response was not significantly different between the three groups. Discrimination between groups could not be improved by measurements of HVR during exercise (50% maximum oxygen consumption (V'O2,max)), or by assessing ventilation and oxygen saturation during a 15 min steady-state exercise (35% V'O2,max) at fractional inspiratory oxygen (FI,O2) of 0.14. Pulmonary artery pressure (Ppa) estimated by Doppler measurements of tricuspid valve pressure at an FI,O2 of 0.21 and 0.12 (10 min) did not lead to a further discrimination between subjects susceptible to HAPE and AMS with the exception of three subjects susceptible to HAPE who showed an exaggerated HPVR. It is concluded that a low ventilatory response to hypoxia is associated with an increased risk for high altitude pulmonary oedema, whilst susceptibility to acute mountain sickness may be associated with a high or low ventilatory response to hypoxia. A reliable discrimination between subjects susceptible to high altitude pulmonary oedema and acute mountain sickness with a low ventilatory response to hypoxia is not possible by Doppler echocardiographic estimations of hypoxic pulmonary vascular response.
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PMID:Ventilatory and pulmonary vascular response to hypoxia and susceptibility to high altitude pulmonary oedema. 862 Sep 46

Both the transient hypoxic ventilatory drive test and the single-breath carbon dioxide (CO2) response test have been used to assess peripheral chemoreflex sensitivity. We tested their comparability in 14 healthy adults (10 men, aged 31-73 years, mean 55.4 years). The within-subject reproducibility of both tests was also assessed (n = 7 for each). The mean transient hypoxic ventilatory response was 0.287 +/- 0.0591 min-1 (%Sao2)-1 (mean +/- SEM, range 0.018- 0.718) and single-breath CO2 response was 0.276 +/- 0.0411 min-1T-1 (range 0.081-0.501). Both tests were reproducible with a mean coefficient of variation of 20.1% and 17.7%, respectively. There was, however, no significant correlation between the results of the transient hypoxic and single-breath CO2 tests when data were compared by linear regression analysis (r = 0.23, P = 0.43), suggesting that separate pathways of the peripheral chemoreflex existed for hypoxia and hypercapnia, respectively, and that these tests were specific for each. The authors conclude that these tests are reproducible but need to be used in combination for an adequate assessment of the peripheral chemoreflex.
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PMID:The reproducibility and comparability of tests of the peripheral chemoreflex: comparing the transient hypoxic ventilatory drive test and the single-breath carbon dioxide response test in healthy subjects. 871 26


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