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)

Recent studies suggest that activation of the sympathetic nervous system either directly or indirectly influences cerebrovascular tone in humans even within the autoregulatory range. In 6 healthy subjects (aged 29+/-4 years), we used transcranial Doppler sonography to determine cerebral blood flow velocity during sympathetic activation elicited through head-up tilt (HUT) and sympathetic deactivation through ganglionic blockade. PaCO(2) was manipulated through hyperventilation and CO(2) breathing (5%). With subjects in the supine position and during HUT, mean arterial pressure was not influenced by PaCO(2). During ganglionic blockade, mean arterial pressure decreased markedly with hyperventilation (-13+/-1.9 mm Hg). Manipulation of sympathetic tone elicited only mild changes in cerebral blood flow (64+/-5.8 cm/s supine, 58+/-4.9 cm/s upright, and 66+/-6.2 cm/s during ganglionic blockade; P:=0.07 by ANOVA). The slope of the regression between PaCO(2) and mean velocity was 1.6+/-0.18 cm/(s. mm Hg) supine, 1.3+/-0.14 cm/(s. mm Hg) during HUT, and 2.3+/-0.36 cm/(s. mm Hg) during ganglionic blockade (P:<0.05). Spontaneous PaCO(2) and ventilatory response to hypercapnia were also modulated by the level of sympathetic activity. Changes in sympathetic tone have a limited effect on cerebral blood flow at normal PaCO(2) levels. However, the sympathetic nervous system seems to attenuate the CO(2)-induced increase in cerebral blood flow. This phenomenon may indicate a moderate direct effect of the sympathetic nervous system on the cerebral vasculature. Furthermore, sympathetic activation tends to increase ventilation and thus can indirectly increase cerebrovascular tone.
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PMID:Interaction of carbon dioxide and sympathetic nervous system activity in the regulation of cerebral perfusion in humans. 1098 69

We investigated the hypothesis that lung blood flow distribution is modified in stage 1 chronic obstructive pulmonary disease (COPD). We compared patients with stage 1 COPD (n = 11) with restrictive patients with comparable blood gases (n = 7), to patients with low cardiac index with normal lungs (n = 11) and to control subjects (n = 11). Distribution of transit time (DTT) was computed by deconvolution from first pass radioactivity curves (albumin (99m)Tc) reconstructed from right and left ventricular regions of interest. Distribution descriptors, mean transit time (p < 0.05), standard deviation (p < 0.001), relative dispersion (p < 0.001), and kurtosis (p < 0.001) differed between groups (ANOVA). Cardiac index was the same in COPD and low CI groups but lower compared with normal subjects (p < 0.05). After normalization for cardiac output, the DTT of patients with COPD remained different from low CI and restrictive patients (p < 0.001). Therefore changes in DTT in patients with COPD compared with patients without COPD could not be explained on the basis of difference in cardiac output. Because P(O(2)), PC(O(2)), and pH were similar in COPD and restrictive groups, difference in distribution could not be explained either on the basis of blood gas data. We conclude that changes in DTT occurs in stage 1 COPD and cannot be explained by hypoxemia, hypercapnia, or acidosis alone but must relate to other structural or regulatory responses.
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PMID:Pulmonary blood flow distribution in stage 1 chronic obstructive pulmonary disease. 1111 17

Bilirubin appears to be toxic in vitro to several cellular functions localized to different subcellular compartments. It would therefore be useful to know what concentrations of bilirubin might be found in cell organelles in vivo. Rats were anesthetized and allocated to one of three groups: control, hypercarbia, and hyperosmolality. Each rat received a 5-min bolus dose of bilirubin 50 mg/kg i.v. (containing approximately 200 microCi [(3)H]bilirubin). Rats were killed 10 or 30 min after the start of the bilirubin infusion. Each brain was homogenized, and subcellular fractions were isolated by high-speed gradient centrifugation in sucrose media. The gradients were separated into aliquots of 2 mL, and the protein content was determined in each aliquot. Radioactivity was determined by scintillation counting, and the content of bilirubin per milligram of protein was calculated. Statistical comparisons were performed with Kruskal-Wallis nonparametric ANOVA. There were highly significant differences in bilirubin content per milligram of protein among subcellular compartments in all groups and at both time points. In all groups there were relatively high concentrations of bilirubin in the myelin fraction, an interesting observation in light of the theory that membranes are the primary target of bilirubin toxicity. The very high concentration of bilirubin relative to protein in cytoplasm, ribosomes, and mitochondria in the hyperosmolar group are also notable in light of data from hyperbilirubinemic animals in which changes in electrophysiology or energy metabolism only appeared after hyperosmolar opening of the blood-brain barrier. The present data may be useful in planning in vitro studies of bilirubin toxicity in cell organelles.
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PMID:Subcellular localization of bilirubin in rat brain after in vivo i.v. administration of [3H]bilirubin. 1115 14

Ventilatory responses (VRs) were measured via a sealed face mask and pneumotachograph in 30 unsedated, mixed-breed miniature piglets at 12.6 +/- 2.3 days of age (day 1) and then repeated after seven daily 24-min exposures to 10% O(2)-6% CO(2) [hypercapnic hypoxia (HH)]. Arterial blood was sampled at baseline, after 10 min of exposure, and after 10 min of recovery. VRs included hypoxia (10% O(2) in N(2)), hypercapnia (6% CO(2) in air), and HH (10% O(2)-6% CO(2)-balance N(2)). Treatment groups (n = 10 each) were exposed to 24 min of HH from day 2 to 8 as sustained HH (24 min of HH and then 24 min of air) or cyclic HH (4 min of HH alternating with 4 min of air). Day 1 and 9 data were compared in treatment and control groups. After cyclic HH, respiratory responses to CO(2) were reduced during hypercapnia and during HH (P < 0.001 vs. control for minute ventilation in both). In both treatment groups, time to peak minute ventilation was delayed in hypoxia (P = 0.02, ANOVA), and response amplitude was increased (P < 0.001 and P = 0.003, sustained and cyclic HH, respectively, vs. control). Respiratory pattern was also altered during the VRs and among treatment groups. Stimulus presentation characteristics exert effects on VRs that are independent of those elicited by daily HH.
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PMID:Depression of ventilatory responses after daily, cyclic hypercapnic hypoxia in piglets. 1118 21

Modulation of heart rate (HR) during transient hyperoxia, hypoxia, and hypercapnia was studied in 46 healthy term infants on 103 occasions (postnatal d 2 to 82). Twenty-three infants had smoking mothers (median, 11 cigarettes/d). Transient chemoreceptor stimuli (100% O(2), 15% O(2), or 3% CO(2)) were presented repeatedly during quiet sleep. Beat-by-beat HR and breath-by-breath ventilation were recorded continuously. The coherently averaged HR and ventilation responses to each stimulus were calculated for each infant at each age. Outcome variables (HR change from baseline to end of stimulation, maximum HR change, and time to half-maximum) were analyzed by ANOVA. Overall, HR declined during hyperoxia (median change, 4.2 beats/min) and rose during hypoxia (median change, 4.2 beats/min) and hypercapnia (median change, 4.6 beats/min). The percentage change in HR was positively correlated with the percentage change in ventilation (p < 0.001). Increasing number of cigarettes smoked by the mother was correlated with deeper HR declines and smaller HR rises (p = 0.02). For the population as a whole, the HR response lagged 3.8 s behind the ventilatory response during hyperoxia and hypoxia (p < 0.001), whereas during hypercapnia there was no significant lag. The lag in HR response in the smoke-exposed group was 2.5 s greater than that in the control group for all three stimuli (p = 0.001), and the difference increased with the number of cigarettes smoked by the mother (p < 0.01). Both pulmonary reflexes and the type of the chemoreceptor stimulus seemed to influence HR. Maternal smoking affected the magnitude and time-course of the HR response in a dose-dependent manner.
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PMID:Heart rate response to transient chemoreceptor stimulation in term infants is modified by exposure to maternal smoking. 1126 41

Patients suffering from neuromuscular diseases and thoracic deformities may develop global respiratory failure during their illness. We wanted to judge clinical parameters and information from the patients' medical history to reliably, quickly and noninvasively diagnose a ventilatory failure. Therefore we evaluated 105 situations with and without mechanical ventilation from 29 patients with indication for noninvasive nocturnal mask ventilation. 6 clinical parameters (e.g. heart rate, oxygen saturation, relative vital capacity), 2 test results (pH and partial pressure of carbon dioxide (pCO2)) and 6 parameters from the patients' medical history (e.g. nycturia, frontal headache in the morning, breathlessness) were investigated. After statistical evaluation we could show a relation between heart rate and pCO2 (Spearman's correlation: r = 0.331, p = 0.001, n = 105; one-tailed significance: r = 0.335, p = 0.038, n = 29). Significant differences between the groups of nycturia incidence indicate a tight relation between the incidence of nycturia and the height of hypercapnia levels (ANOVA--analysis of variance: p = 0.001). Using logistic regression we could show that information regarding medical history, especially nycturia, frontal headache and indrawings, gives important indications for global respiratory failure (sensitivity 97.62-100%, specificity 57.14-76.19%). Pathogenesis needs to be elaborated further.
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PMID:[Importance of medical history in diagnosis of respiratory insufficiency in patients suffering from neuromuscular diseases and thoracic deformities]. 1138 81

We performed a randomized, cross-over controlled trial to assess the effect of Oleoresin capsicum (OC) spray inhalation on respiratory function by itself and combined with restraint. Thirty-five subjects were exposed to OC or placebo spray, followed by 10 min of sitting or prone maximal restraint position (PMRP). Spirometry, oximetry, and end-tidal CO2 levels were collected at baseline and throughout the 10 min. Data were compared between groups (ANOVA) and with predefined normal values. In the sitting position, OC did not result in any significant changes in mean percent predicted forced vital capacity (%predFVC), percent predicted forced expiratory volume in 1 s (%predFEV1), oxygen, or CO2 levels. In PMRP, mean %predFVC and %predFEV1 fell 14.4 and 16.5% for placebo and 16.2 and 19.1% for OC, but were not significantly different by exposure. There was no evidence of hypoxemia or hypercapnia in either groups. OC exposure did not result in abnormal spirometry, hypoxemia, or hypoventilation when compared to placebo in either sitting or PMRP.
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PMID:The effect of oleoresin capsicum "pepper" spray inhalation on respiratory function. 1190 98

Severely premature infants are often at increased risk of cerebral hemorrhage and/or ischemic injury caused by immature autoregulatory control of blood flow to the brain. If blood flow is too high, the infant is at risk of hemorrhage, whereas too little blood flow can result in ischemic injury. The development of a noninvasive, bedside means of measuring cerebral hemodynamics would greatly facilitate both diagnosis and monitoring of afflicted individuals. It is to this end that we have developed a near infrared spectroscopy (NIRS) system that allows for quantitative, bedside measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). The technique requires an i.v. injection of the near infrared chromophore indocyanine green. Six newborn piglets, median age of 18 h (range 6-54 h), median weight of 1.75 kg (range 1.5-2.1 kg), were studied. Measurements of CBF, CBV, and MTT were made at normocapnia, hypocapnia, and hypercapnia to test the technique over a range of hemodynamic conditions. The accuracy of our new approach has been determined by direct comparison with measurements made using a previously validated computed tomography technique. Paired t tests showed no significant difference between computed tomography and NIRS measurements of CBF, CBV, and MTT, and mean biases between the two methods were -2.05 mL x min(-1) x 100 g(-1), -0.18 mL x 100 g(-1), and 0.43 s, respectively. The precision of NIRS CBF, CBV, and MTT measurements, as determined by repeated-measures ANOVA, was 9.71%, 13.05%, and 7.57%, respectively.
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PMID:Quantitative near infrared spectroscopy measurement of cerebral hemodynamics in newborn piglets. 1197 78

Intracellular factors that regulate nitric oxide (NO) synthesis represent important targets in tumor progression. Overexpression of dimethylarginine dimethylaminohydrolase (DDAH), which metabolizes the endogenous inhibitors of NO synthesis asymmetric dimethylarginine and N-monomethyl-L-arginine, results in C6 gliomas with enhanced growth rate compared with wild type. To investigate the effects of DDAH on tumor vascular morphogenesis in vivo, we have measured the transverse relaxation rates R(2)* and R(2) in clone D27 gliomas overexpressing DDAH and C6 wild-type gliomas using intrinsic susceptibility magnetic resonance imaging (MRI), sensitive to changes in endogenous [deoxyhemoglobin], and susceptibility contrast-enhanced MRI using the intravascular blood pool contrast agent NC100150, and we compared the results with fluorescence microscopy of the tumor uptake of the perfusion marker Hoechst 33342. The baseline R(2)* was significantly faster in the D27 tumors, consistent with a greater vascular development (P < 0.02, ANOVA). There was no significant difference between the response of the two tumor types to hypercapnia (5% CO(2)/95% air), used as a probe for vascular maturation, or hyperoxia (5% CO(2)/95% O(2)), used as a probe for vascular function. NC100150 increased the R(2)* and R(2) rates of both tumor types and demonstrated a significantly larger blood volume in the D27 tumors (P < 0.02, ANOVA). This correlated with a significantly greater uptake of Hoechst 33342 in the D27 tumors compared with C6 wild-type tumors (P < 0.02, ANOVA). Despite the increased tumor blood volume, the Delta R(2)*/Delta R(2) ratio, an index of microvessel size, showed that the capillaries in the two tumor types were of a similar caliber. The data highlight the potential of susceptibility MRI-derived quantitative end points to noninvasively assess tumor angiogenesis, and in this regard, the use of intravascular blood pool contrast agents such as NC100150 appears very promising. Overexpression of DDAH results in increased neovascularization of C6 gliomas in vivo. The lack of significant difference in hypercapnic/hyperoxic response between the C6 and D27 tumors and the similar vessel caliber are also consistent with a role for DDAH in the initial stages of vasculogenesis.
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PMID:Effects of overexpression of dimethylarginine dimethylaminohydrolase on tumor angiogenesis assessed by susceptibility magnetic resonance imaging. 1294 21

Whereas peripheral chemoreceptor oxygen sensitivity increases markedly after birth, previous studies of ventilatory responses to CO(2) in term infants have shown no postnatal development. However, the hypercapnic challenges applied have usually been long-term, which meant that the effect of central chemoreceptors dominated. Oscillatory breathing, apneas, and sighs cause transient Pco(2) changes, probably primarily stimulating peripheral chemoreceptors. We wanted to assess whether the immediate ventilatory responses to step changes in inspired CO(2) and O(2) in term infants undergo postnatal developmental changes. Twenty-six healthy term infants were studied during natural sleep 2 d and 8 wk postnatally. Ventilatory responses to a randomized sequence of 15 s hypercapnia (3% CO(2)), hypoxia (15% O(2)), and hypercapnic hypoxia (3% CO(2) + 15% O(2)) were recorded breath-by-breath using a pneumotachometer. Response rate, stimulus-response time, and response magnitude were analyzed with ANOVA after coherent averaging. Response rate increased with age by 30% (hypercapnia), 318% (hypoxia), and 302% (hypercapnic hypoxia). Response rate during hypercapnic hypoxia exceeded rate during hypercapnia plus rate during hypoxia in wk 8, but not on d 2. Time to half-maximum response decreased by 3.4 s with age for the two hypercapnic stimuli but was unchanged for hypoxia. Response magnitude was unchanged for hypercapnia, but increased for the two hypoxic stimuli. In conclusion, an interaction between the effects of hypercapnia and hypoxia on ventilatory response rate emerged between postnatal d 2 and wk 8 in term infants. Concomitantly, stimulus-response time to hypercapnic stimuli declined markedly. The development of a prompt response to transient hypercapnia may be important for infant respiratory stability.
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PMID:Development of ventilatory response to transient hypercapnia and hypercapnic hypoxia in term infants. 1463 Sep 82


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