UMLS:C0020440 - FACTA Search

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

Current recommendations for mechanical ventilation in the acute respiratory distress syndrome (ARDS) include the use of small tidal volumes (VT), even at the cost of respiratory acidosis. We evaluated the effects of this permissive hypercapnia on pulmonary gas exchange with the multiple inert gas elimination technique (MIGET) in eight patients with ARDS. After making baseline measurements, we induced permissive hypercapnia by reducing VT from 10 +/- 2 ml/kg to 6 +/- 1 ml/kg (mean +/- SEM) at constant positive end-expiratory pressure. After restoration of initial VT, we infused dobutamine to increase cardiac output (Q) by the same amount as with hypercapnia. Permissive hypercapnia increased Q by an average of 1.4 L. min(-)(1). m(2), decreased arterial oxygen tension from 109 +/- 10 mm Hg to 92 +/- 11 mm Hg (p < 0.05), markedly increased true shunt (Q S/Q T), from 32 +/- 6% to 48 +/- 5% (p < 0.0001), and had no effect on the dispersion of VA/Q.VA/Q. On reinstatement of baseline V T with maintenance of a high Q, Q S/Q T remained increased, to 38 +/- 6% (p < 0.05), and Pa(O(2 ))remained decreased, to 93 +/- 4 mm Hg (p < 0. 05). These results agreed with effects of changes in VT and Q predicted by the mathematical lung model of the MIGET. We conclude that permissive hypercapnia increases pulmonary shunt, and that deterioration in gas exchange is explained by the combined effects of increased Q and decreased alveolar ventilation.
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PMID:Permissive hypercapnia impairs pulmonary gas exchange in the acute respiratory distress syndrome. 1090 43

How do the respiratory centres of patients with chronic obstructive pulmonary disease (COPD) and hypercapnia respond to acute increases in inspiratory load? A depressed respiratory motor output has long been postulated, but studies on this issue have yielded inconsistent results, partly due to limitations of investigative techniques. Many of these limitations can be overcome by the twitch interpolation technique, which is capable of accurately quantifying the degree of diaphragmatic activation, termed the voluntary drive to breathe. The hypothesis that patients with COPD and hypercapnia compensate for an acute increase in mechanical load on the inspiratory muscles with a lower voluntary drive to breathe than is the case with normocapnic patients was tested. Measurements were obtained in 15 patients with COPD, six of whom displayed hypercapnia and nine normocapnia. The maximum degree of diaphragmatic activation, expressed as a voluntary activation index (mean +/- SEM), was higher in hypercapnic than in normocapnic patients (98.7 +/- 0.7 versus 94.5 +/- 0.9% (p = 0.006)), as was the mean value (94.5 +/- 0.7 versus 88.5 +/- 1.9% (p = 0.01)). Within-patient values of the index were also less variable in the hypercapnic patients (coefficients of variation, 3.4 +/- 0.3 versus 6.1 +/- 0.9%, p = 0.01). Multiple regression analysis revealed the ratio of dynamic elastance to maximum transdiaphragmatic pressure, an index of inspiratory muscle loading, and pH as the only variables that correlated with maximum voluntary activation index (r2 = 0.69, p = 0.02 for each variable). Contrary to the hypothesis, it was concluded that voluntary activation of the diaphragm was greater and less variable in hypercapnic patients than normocapnic patients with severe chronic obstructive pulmonary disease during an acute increase in inspiratory mechanical load. Whether greater diaphragmatic recruitment during episodes of a severe exacerbation of chronic obstructive pulmonary disease provides a survival advantage for hypercapnic patients with chronic obstructive pulmonary disease remains to be determined.
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PMID:The voluntary drive to breathe is not decreased in hypercapnic patients with severe COPD. 1151 Aug 6

To investigate whether respiratory acidosis modulates ventilator-induced lung injury (VILI), we perfused (constant flow) 21 isolated sets of normal rabbit lungs, ventilated them for 20 min (pressure controlled ventilation [PCV] = 15 cm H(2)O) (Baseline) with an inspired CO(2) fraction adjusted for the partial pressure of CO(2) in the perfusate (PCO(2) approximately equal to 40 mm Hg), and then randomized them into three groups. Group A (control: n = 7) was ventilated with PCV = 15 cm H(2)O for three consecutive 20-min periods (T1, T2, T3). In Group B (high PCV/normocapnia; n = 7), PCV was given at 20 (T1), 25 (T2), and 30 (T3) cm H(2)O. The targeted PCO(2) was 40 mm Hg in Groups A and B. Group C (high PCV/hypercapnia; n = 7) was ventilated in the same way as Group B, but the targeted PCO(2) was approximately equal to 70 to 100 mm Hg. The changes (from Baseline to T3) in weight gain (Delta WG: g) and in the ultrafiltration coefficient (Delta K(f) = gr/min/ cm H(2)O/100g) and the protein and hemoglobin concentrations in bronchoalveolar lavage fluid (BALF) were used to assess injury. Group B experienced a significantly greater Delta WG (14.85 +/- 5.49 [mean +/- SEM] g) and Delta K(f) (1.40 +/- 0.49 g/min/cm H(2)O/100 g) than did either Group A (Delta WG = 0.70 +/- 0.43; Delta K(f) = 0.01 +/- 0.03) or Group C (Delta WG = 5.27 +/- 2.03 g; Delta K(f) = 0.25 +/- 0.12 g/min/cm H(2)O/ 100 g). BALF protein and hemoglobin concentrations (g/L) were higher in Group B (11.98 +/- 3.78 g/L and 1.82 +/- 0.40 g/L, respectively) than in Group A (2.92 +/- 0.75 g/L and 0.38 +/- 0.15 g/L) or Group C (5.71 +/- 1.88 g/L and 1.19 +/- 0.32 g/L). We conclude that respiratory acidosis decreases the severity of VILI in this model.
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PMID:Protective effects of hypercapnic acidosis on ventilator-induced lung injury. 1154 36

In severe chronic obstructive pulmonary disease (COPD), carbon dioxide retention during exercise is highly variable and is poorly predicted by resting pulmonary function and arterial blood gases or by tests of ventilatory control. We reasoned that in patients with compromised gas exchange capabilities, exercise hypercapnia could be explained, in part, by the restrictive consequences of dynamic lung hyperinflation. We studied 20 stable patients with COPD (FEV(1) = 34 +/- 3 percent predicted; mean +/- SEM) with varying gas exchange abnormalities (Pa(O(2)) range, 35 to 84 mm Hg; Pa(CO(2)) range, 31 to 64 mm Hg). During symptom-limited maximum cycle exercise breathing room air, Pa(CO(2)) increased 7 +/- 1 mm Hg (p < 0.05) from rest to peak exercise (range, -6 to 25 mm Hg). We measured the change in Pa(CO(2)) after hyperoxic breathing at rest as an indirect test of ventilation-perfusion abnormalities. The change in Pa(CO(2)) from rest to peak exercise correlated best with the acute change in Pa(CO(2)) during hyperoxia at rest (r(2) = 0.62, p < 0.0005) and with resting arterial oxygen saturation (r(2) = 0.30, p = 0.011). During exercise, the strongest correlates of serial changes in Pa(CO(2)) from rest included concurrent changes in end-expiratory lung volume expressed as a percentage of total lung capacity (partial correlation coefficient [r] = 0.562, p < 0.0005) and oxygen saturation (partial r = 0.816, p < 0.0005). In severe COPD, the propensity to develop carbon dioxide retention during exercise reflects marked ventilatory constraints as a result of lung hyperinflation as well as reduced gas exchange capabilities.
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PMID:Exercise hypercapnia in advanced chronic obstructive pulmonary disease: the role of lung hyperinflation. 1220 54

Chemoreceptors in the ventral medulla contribute to the respiratory response to hypercapnia. Do they 'sense' intracellular pH (pHi)? We measured pHi in the ventral medulla or cortex (control) using 31P-NMR obtained via a novel 3 x 5 mm2 surface coil in anesthetized rats breathing air or 7% CO2. During air breathing over 240 min, pHi decreased slightly from 7.13 +/- 0.02 to 7.05 +/- 0.02 (SEM; n = 5; 2 cortex, 3 ventral medulla). During 180 min of hypercapnia, cortical pHi (n = 4) decreased from 7.17 +/- 0.02 to 6.87 +/- 0.01 by 90 min and recovered by 150 min. Ventral medulla pHi showed no such regulation. It decreased from 7.11 +/- 0.02 to 6.88 +/- 0.02 at 90 min and recovered only after cessation of hypercapnia (n = 5), results consistent with pHi being the chemoreceptor stimulus. However, non-chemoreceptor neurons that contribute to our medullary NMR signal also do not appear to regulate pHi in vitro. Regional differences in pHi regulation between cortex and ventral medulla may be due to both chemosensitive and non-chemosensitive neurons.
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PMID:Ventral medulla pHi measured in vivo by 31P NMR is not regulated during hypercapnia in anesthetized rat. 1238 4

We stimulate single central chemoreceptor sites in the unanesthetized rat by focal microdialysis of artificial cerebrospinal fluid (aCSF) equilibrated with 25% CO(2). Here, in the retrotrapezoid nucleus (RTN) we measured the focal stimulus intensity with a pH electrode adjacent to the dialysis probe. During 25% CO(2) dialysis, RTN pH decreased by 0.069 (0.013, SEM) pH units (N=5), 44% of the change observed during 7% CO(2) breathing, -0.157 (0.019) pH units (N=4). During 7% CO(2) breathing, Pa(CO(2)) increased by 15 Torr (N=5). We calculate the deltaPa(CO(2)) that would produce a deltapH at the RTN approximately like that observed during 25% CO(2) dialysis as 44% of 15 Torr, or 6.6 Torr deltaPa(CO(2)). Using ventilatory response data from our lab, we estimate overall chemoreceptor sensitivity as 13% deltaVE/Torr deltaPa(CO(2)) and RTN sensitivity as 3% deltaVE/Torr deltaPa(CO(2)). The RTN provides 23% of the overall response. This may be an underestimate. During RTN stimulation Pa(CO(2)) decreases by 4.9 (0.7) Torr (N=5), which may inhibit other chemoreceptor sites. Multiple chemoreceptor sites may interact to provide high sensitivity in systemic hypercapnia and stability during heterogeneous stimulation and inhibition.
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PMID:CO2 dialysis in one chemoreceptor site, the RTN: stimulus intensity and sensitivity in the awake rat. 1238 27

In this study, we examined the cardiorespiratory patterns of harbour seal pups under normoxic/normocarbic (air), hypoxic/normocarbic (15%, 12%, and 9% O2 in air), and normoxic/hypercarbic (2%, 4%, and 6% CO2 in air) conditions while awake and sleeping on land. Animals were chronically instrumented to record electroencephalogram (EEG), electromyogram (EMG), and electrocardiogram (EKG) signals, which, along with respiration (whole-body plethysmography) and oxygen consumption (VO2), were recorded from animals breathing each gas mixture for 2-4 h on separate days. Our results show that for animals breathing air, VO2 was not significantly lower during slow-wave sleep (SWS; 7.71 +/- 0.39 mL O2 min(-1) kg(-1); all measurements are mean +/- SEM) than during wakefulness (WAKE; 8.80 +/- 0.25 mL O2 min(-1) kg(-1)) and was unaffected by changes in respiratory drive. Although there was no significant fall in VO2 associated with a decrease in arousal state, breathing frequency (f(R)) did decrease (from 18.80 +/- 1.50 breaths min(-1) in WAKE to 10.40 +/- 0.49 breaths min(-1) in SWS), while the incidence of long apneas (>20 s) increased (12.76 +/- 4.06 apneas h(-1) in WAKE and 31.95 +/- 2.37 apneas h(-1) in SWS). Breathing was rarely seen during rapid eye movement (REM) sleep. Tachypnea was present at all levels of increased respiratory drive; however, hypoxia induced a dramatic bradycardia regardless of arousal state, while hypercarbia produced a tachycardia in SWS only. The hypoxic and hypercarbic chemosensitivities of harbour seal pups were similar to those of terrestrial mammals; however, unlike terrestrial mammals, where hypoxic and hypercarbic sensitivities are often reduced during SWS, the sensitivity of harbour seal pups to hypoxia and hypercarbia remained unchanged during the decrease in arousal state from WAKE to SWS.
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PMID:Respiratory chemosensitivity during wake and sleep in harbour seal pups (Phoca vitulina richardsii). 1554 2

Sympathetic activation and sleep apnea are present in most patients with symptomatic systolic heart failure (HF). Acutely, obstructive and central apneas increase muscle sympathetic activity (MSNA) during sleep by eliciting recurrent hypoxia, hypercapnia, and arousal. In obstructive sleep apnea patients with normal systolic function, this increase persists after waking. Whether coexisting sleep apnea augments daytime MSNA in HF is unknown. We tested the hypothesis that its presence exerts additive effects on MSNA during wakefulness. Overnight sleep studies and morning MSNA recordings were performed on 60 subjects with ejection fraction <45%. Of these, 43 had an apnea-hypopnea index > or =15 per hour. Subjects with and subjects without sleep apnea were similar for age, ejection fraction, HF etiology, body mass index, blood pressure, and heart rate. Daytime MSNA was significantly higher in those with sleep apnea (76+/-2 versus 63+/-4 bursts per 100 heartbeats [mean+/-SEM], P=0.005; 58+/-2 versus 50+/-3 bursts/min, P=0.037), irrespective of its etiology (the mean difference for central sleep apnea was 17 bursts per 100 heartbeats; n=14; P=0.006; and for obstructive sleep apnea, 11 bursts per 100 heartbeats; n=29; P=0.032). In a subgroup (n=8), treatment of obstructive sleep apnea lowered MSNA by 12 bursts per 100 heartbeats (P=0.003). Convergence of independent excitatory influences of HF and sleep apnea on central sympathetic neurons results in higher MSNA during wakefulness in HF patients with coexisting sleep apnea. This additional stimulus to central sympathetic outflow may accelerate the progression of HF; its attenuation by treatment of sleep apnea represents a novel nonpharmacological opportunity.
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PMID:Muscle sympathetic nerve activity during wakefulness in heart failure patients with and without sleep apnea. 1628 69

Pulmonary neuroendocrine cells (PNEC), including neuroepithelial bodies (NEB), are amine- and peptide (for example, bombesin)-producing cells that function as hypoxia/hypercapnia-sensitive chemoreceptors that could be involved in the pathophysiology of sudden infant death syndrome (SIDS). We assessed morphometrically the frequency and size of PNEC/NEB in lungs of infants who died of SIDS (n = 21) and compared them to an equal number PNEC/NEB in lungs of age-matched control infants who died of accidental death or homicide, with all cases obtained from the San Diego SIDS/SUDC Research Project database. As a marker for PNEC/NEB we used an antibody against chromogranin A (CGA), and computer-assisted morphometric analysis was employed to determine the relative frequency of PNEC per airway epithelial area (% immunostained area, %IMS), the size of NEB, the number of nuclei/NEB, and the size of the NEB cells. The lungs of SIDS infants showed significantly greater %IMS of airway epithelium (2.72 +/- 0.28 [standard error of the mean, SEM] versus 1.88 +/- 0.24; P < 0.05) and larger NEB (1557 +/- 153 microm(2) versus 1151 +/- 106 microm(2); P < 0.05) compared to control infants. The size of NEB cells was also significantly increased in SIDS cases compared to the controls (180 +/- 6.39 microm(2) versus 157 +/- 8.0 microm(2); P < 0.05), indicating the presence of hypertrophy in addition to hyperplasia. Our findings support previous studies demonstrating hyperplasia of PNEC/NEB in lungs of infants who died of SIDS. These changes could be secondary to chronic hypoxia and/or could be attributable to maturational delay. Morphometric assessment and/or measurement of the secretory products of these cells (for example, CGA, bombesin) could provide a potential biological marker for SIDS.
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PMID:Pulmonary neuroendocrine cells and neuroepithelial bodies in sudden infant death syndrome: potential markers of airway chemoreceptor dysfunction. 1737 91

Changes in breathing change the concentration of oxygen and carbon dioxide in arterial blood resulting in changes in cerebral blood flow (CBF). This mechanism can be described by the cerebral vascular response (CVR), which has been shown to be altered in different physiological and pathophysiological states. CBF maps of grey matter (GM) were determined with a pulsed arterial spin labelling technique at 3 T in a group of 19 subjects under baseline conditions, hypoxia, and hypercapnia. Experimental conditions allowed a change in either arterial oxygen (hypoxia) or carbon dioxide (hypercapnia) concentration compared with the baseline, leaving the other variable constant, in order to separate the effects of these two variables. From these results, maps were calculated showing the regional distribution of the CVR to hypoxia and hypercapnia in GM. Maps of CVR to hypoxia showed very high intra-subject variations, with some GM regions exhibiting a positive response and others a negative response. Per 10% decrease in arterial oxygen saturation, there was a statistically significant 7.0 +/- 2.9% (mean +/- SEM) increase in GM-CBF for the group. However, 70% of subjects showed an overall positive CVR (positive responders), and the remaining 30% an overall negative CVR (negative responders). Maps of CVR to hypercapnia showed less intra-subject variation. Per 1 mm Hg increase in partial pressure of end-tidal carbon dioxide, there was a statistically significant 5.8 +/- 0.9% increase in GM-CBF, all subjects showing an overall positive CVR. As the brain is particularly vulnerable to hypoxia, a condition associated with cardiorespiratory diseases, CVR maps may help in the clinic to identify the areas most prone to damage because of a reduced CVR.
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PMID:Mapping of the cerebral vascular response to hypoxia and hypercapnia using quantitative perfusion MRI at 3 T. 1785 23

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