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)

Chronic lung disease (CLD) of prematurity is a common disorder in preterm infants who were ventilated for respiratory distress syndrome (RDS) at birth. Premature birth, mechanical ventilation and supplemental oxygen are the major risk factors for the development of CLD. Although the exact pathophysiology is unclear, recent evidence suggests that pulmonary inflammation may play a pivotal role in the development of CLD. Histologically, the evolution of CLD can be divided into an early inflammatory phase followed by a subacute and chronic fibroproliferative phase. The early, inflammatory phase of CLD is clinically indistinguishable from RDS. In bronchoalveolar lavage fluid an influx of inflammatory cells and increased levels of cytokines can be found. Pathological examination of the lungs reveals persisting hyaline membranes, necrosis of airway and alveolar epithelium and an influx of inflammatory cells in the lung. In the subacute fibroproliferative or reparative phase of CLD, persistent respiratory distress and hypercapnia are seen and patients require oxygen with or without ventilatory support. Histologically, this phase is characterized by hyperplasia of type II pneumocytes, hypertrophy of bronchial and bronchiolar smooth muscle and interstitial and perialveolar fibrosis. In the chronic fibroproliferative phase (up to 1 yr), airway remodelling occurs. Respiratory distress continues and many patients remain oxygen dependent. Cyanotic spells are frequently seen and chronic hypoxia may lead to pulmonary hypertension and right heart failure. Many patients have severe feeding problems and somatic growth is poor. In surviving patients, persisting lung function abnormalities are found. Airway resistance and airway responsiveness are increased and residual volume (RV) and RV/total lung capacity ratios remain elevated, indicating air trapping. Although lung function improves during childhood, residual abnormalities are still found in young adults, raising concerns about the evolution of pulmonary function in old age.
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PMID:Evolution and natural history of chronic lung disease of prematurity. 927 Feb 56

It has previously been reported that active glottic adduction is present during prolonged apneas but absent during periods of breathing movements in fetal lambs in utero. The present study was aimed at examining the precise coordination between fetal breathing movements [diaphragm electromyographic (EMG) activity (Di EMG)] and glottic adduction [thyroarytenoid muscle EMG activity (TA EMG)]. Electrodes for electroencephalogram, eye movements, TA EMG, and Di EMG and an arterial catheter were surgically implanted in fetal lambs 123-142 days postconception. Polygraphic recordings were performed without sedation while the ewe breathed room air (n = 11) or various gas mixtures (hypoxia, n = 5; hyperoxia, n = 4; hypercapnia, n = 5; hypercapnia+hyperoxia, n = 5). Tonic TA EMG was observed throughout >90% of apneas (>6 s) in both non-rapid-eye-movement and rapid-eye-movement sleep, and when Di EMG frequency decreased in rapid-eye-movement sleep. In all but two fetuses, TA EMG was immediately inhibited when Di EMG appeared. Altering blood gases did not modify these results. In conclusion, Di EMG and TA EMG are well coordinated in late gestation in fetal lambs, except in a few cases. These findings may have consequences for understanding the pathogenesis of mixed/obstructive apneas of prematurity.
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PMID:Coordination between glottic adductor muscle and diaphragm EMG activity in fetal lambs in utero. 957 99

Advances in neonatology have resulted in an increase in the absolute number of survivors with chronic lung disease (CLD), though its overall incidence has not changed. Though the single most important high-risk factor for CLD is prematurity, the focus of attention has recently changed over to minimizing the impact of other two risk factors: baro/volutrauma related to mechanical ventilation, and oxygen toxicity. Permissive hypercapnia (PHC) or controlled ventilation is a strategy that minimizes baro/volutrauma by allowing relatively high levels of arterial CO(2), provided the arterial pH does not fall below a preset minimal value. The benefits of PHC are primarily mediated by the reduction of lung stretch that occurs when tidal volumes are minimized. PHC can be a deliberate choice to restrict ventilation in order to avoid overdistention, while application of high airway pressures and large tidal volumes would permit normocapnia, or relative hypocapnia (PaCO(2), < or = 25-30 mmHg), but may result in CLD and be harmful to the developing lung. The current concept that PaCO(2) levels of 45-55 mmHg in high-risk neonates are "safe" and "well tolerated" is based on limited data. Further prospective trials are needed to study the definition, safety and efficacy of PHC in ventilated preterm and term neonates. However, designing disease/gestational-postnatal age-specific clinical trials of PHC will be difficult in neonates, given the diverse pathophysiology of their diseases and the various ventilatory modes/variables currently available. The potential benefits and adverse effects of PHC are reviewed, and its relationship to current ventilatory strategies like synchronized mechanical ventilation and high-frequency ventilation in high-risk neonates is briefly discussed.
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PMID:Permissive hypercapnia in neonates: the case of the good, the bad, and the ugly. 1174 61

In the perinatal period, glucocorticoids are frequently administered to enhance pulmonary maturity or prevent chronic lung disease of prematurity. Recently, it has been suggested that the perinatal exposure to glucocorticoids can be associated with unfavorable neurologic development. We studied the hypothesis that 24-h pretreatment with glucocorticoid might modify cerebrovascular responses to high and low partial arterial CO(2) tension in newborn animals in vivo. A closed cranial window was implanted over the left parietal cortex of 20 anesthetized ventilated newborn (<3 d old) pigs. The actual experiments were carried out in 15 pigs: eight pretreated with a total dose of 6 mg/kg of dexamethasone and seven controls. Five pigs were used for preliminary experiments as described in the text. Pial arteriolar diameters were measured during 1) baseline conditions (normocapnia), 2) hypercapnia induced by ventilating the animals with a gas mixture containing 10% CO(2), or 3) hyperventilation with resultant hypocapnia. Under these conditions, the concentrations of 6-keto-PGF(1alpha) in the CSF were measured in five experimental animals and six controls. In summary, the dexamethasone pretreatment 1) attenuated the hypercapnia-induced dilator responses of pial arterioles and prevented the hypercapnia-associated fall in mean arterial blood pressure; 2) caused moderate, although not statistically significant, diminution in 6-keto-PGF(1alpha) levels in the CSF during baseline; 3) blocked hypercapnia-induced elevation of 6-keto-PGF(1alpha); and 4) enhanced vasoconstrictive arteriolar responses to hyperventilation. We speculate that in the clinical setting, the dexamethasone effects may compromise the adjustments of global or regional cerebral blood flow to changing physiologic states in neonates.
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PMID:Dexamethasone pretreatment attenuates cerebral vasodilative responses to hypercapnia and augments vasoconstrictive responses to hyperventilation in newborn pigs. 1253 84

High oxygen tension is a major factor in the genesis of retinopathy of prematurity (ROP). However, clinical and experimental evidence suggests a significant role for high carbon dioxide (CO(2)) tension as well. Along these lines, although ischemia is often considered to be synonymous with an oxygen deficit, it is also associated with a concomitant local elevation of CO(2) that can lead to impaired developmental and ischemic neovascularization. The mechanisms by which hypercapnia induces retinal microvascular degeneration, a critical step which precedes the subsequent proliferative preretinal neovascularization, are not known. Nitrative stress has an important role in microvascular degeneration leading to ischemia in conditions such as ROP. Hypercapnia is a facilitator of nitration in vitro. We hereby present evidence that prolonged exposure to CO(2) impairs developmental retinal neovascularization through a mechanism involving increased endothelial nitric oxide synthase and induction of a nitrative stress; effects of hypercapnia are independent of its hyperaemic effects. Moreover, we demonstrate that an in vivo nitrative stress associated with retinal vasoobliteration results in nitration of arachidonic acids into trans-arachidonic acids (TAAs), which can act as mediators of nitrative stress by causing microvascular degeneration by inducing expression of the antiangiogenic factor thrombospondin-1. These recent findings establish a previously unexplored means by which hypercapnia hinders efficient neovascularization and provide new insight into the molecular mechanisms of nitrative stress on microvascular injury involving TAA, and suggest new therapeutic avenues in the management of nitrative stress disorders such as in ischemic retinopathies (of prematurity and of diabetes) and encephalopathies.
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PMID:Hypercapnia- and trans-arachidonic acid-induced retinal microvascular degeneration: implications in the genesis of retinopathy of prematurity. 1681 71

Over the last 15 years, neonatal morbidity and mortality has changed little for very low birth weight babies despite significant technological and therapeutic advances. Bronchopulmonary dysplasia (BPD) continues to be a major problem despite antenatal steroid use, surfactant replacement therapy, gentle noninvasive ventilation techniques, permissive hypercarbia, and judicious use of oxygen. Current evidence supports multiple contributing factors. Prematurity is the cardinal factor; others include pulmonary baro/volutrauma, hyperoxia, and inflammation. BPD is an end product of pulmonary inflammatory response and lung repair with impaired alveolarization and vascularization in response to lung injury. These sequences involve multiple morphoregulatory molecules, which have a range of activities largely determined by genetic variability. A clearer understanding of genetic susceptibility for BPD has recently emerged. Twin studies have shown that the BPD status of one twin, even after correcting for contributing factors, is a highly significant predictor of BPD in the second twin. After controlling for covariates, genetic factors account for 53% (P = 0.004, 95% CI = 16%-89%) of the variance in liability for BPD. Incremental improvements will likely depend on identification of these genetic components for targeting specific therapies.
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PMID:The genetics of bronchopulmonary dysplasia. 1686 Jan 58

Caffeine is commonly used to treat respiratory instabilities related to prematurity. However, the role of adenosinergic modulation and the potential long-term effects of neonatal caffeine treatment (NCT) on respiratory control are poorly understood. To address these shortcomings, we tested the following hypotheses: 1) adenosine A(1)- and A(2A)-receptor antagonists modulate respiratory activity at rest and during hypercapnia; 2) NCT has long-term consequences on adenosinergic modulation of respiratory control. Rat pups received by gavage either caffeine (15 mg/kg) or water (control) once a day from postnatal days 3 to 12. At day 20, rats received intraperitoneal injection with vehicle, DPCPX (A(1) antagonist, 4 mg/kg), or ZM-241385 (A(2A) antagonist, 1 mg/kg) before plethysmographic measurements of resting ventilation, hypercapnic ventilatory response (5% CO(2)), and occurrence of apneas in freely behaving rats. In controls, data show that A(2A), but not A(1), antagonist decreased resting ventilation by 31% (P = 0.003). A(1) antagonist increased the hypercapnic response by 60% (P < 0.001), whereas A(2A) antagonist increased the hypercapnic response by 42% (P = 0.033). In NCT rats, A(1) antagonist increased resting ventilation by 27% (P = 0.02), but the increase of the hypercapnic response was blunted compared with controls. A(1) antagonist enhanced the occurrence of spontaneous apneas in NCT rats only (P = 0.005). Finally, A(2A) antagonist injected in NCT rats had no effect on ventilation. These data show that hypercapnia activates adenosinergic pathways, which attenuate responsiveness (and/or sensitivity) to CO(2) via A(1) receptors. NCT elicits developmental plasticity of adenosinergic modulation, since neonatal caffeine persistently decreases ventilatory sensitivity to adenosine blockers.
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PMID:Disruption of adenosinergic modulation of ventilation at rest and during hypercapnia by neonatal caffeine in young rats: role of adenosine A(1) and A(2A) receptors. 1713 26

High oxygen tension is a major factor in the genesis of retinopathy of prematurity (ROP). However, clinical and experimental evidence also suggest a significant role for high levels of carbon dioxide (CO(2)). Hypercapnia is a facilitator of nitration in vitro, and nitrative stress is known to have an important role in microvascular degeneration leading to ischemia in conditions such as ROP. We hereby present evidence that prolonged exposure to CO(2) impairs developmental retinal neovascularisation through a mechanism involving increased endothelial nitric oxide synthase and induction of a nitrative stress; effects of hypercapnia are independent of its hyperaemic effects. Moreover, in a model of oxygen-induced retinopathy, we demonstrate that an in vivo nitrative stress associated with retinal vasoobliteration results in nitration of cis-arachidonic acids into trans-arachidonic acids (TAAs). TAAs act in turn as mediators of nitrative stress by causing microvascular degeneration by inducing expression of the anti-angiogenic factor thrombospondin-1. These recent findings establish a previously unexplored means by which hypercapnia hinders efficient neovascularisation and provide new insight into the molecular mechanisms of nitrative stress on microvascular injury involving TAA, therefore opening new therapeutic avenues in the management of nitrative stress disorders such as in ischemic retinopathies (of prematurity and of diabetes) and encephalopathies.
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PMID:[Hypercapnia- and trans-arachidonic acid-induced retinal microvascular degeneration: implications in the genesis of retinopathy of prematurity]. 1802 4

Apnea of prematurity (AOP) remains a major clinical problem in present day neonatology that warrants frequent evaluations and imposes challenges in therapeutic strategies. Although the pathogenesis of AOP is poorly understood, it is probably a manifestation of physiologic immaturity of breathing control rather than a pathologic disorder. Immature breathing responses to hypoxia, hypercapnia and exaggerated inhibitory pulmonary reflexes in preterm infants might also contribute to the occurrence or severity of AOP. Recent data suggest a role for genetic predisposition. Although typically resolve with maturation, the role of bradycardia and desaturation episodes associated with AOP in the development of sleep disorder breathing and neurodevelopmental delay needs further clarification. Pharmacological treatment with methylxanthines and CPAP remain the mainstay for treatment of AOP. However, recent studies have implicated central inhibitory neuromodulators including prostaglandins, GABA and adenosine in its pathogenesis, the fact that might provide future specific targets for treatment. This review will summarize new insights involving these issues as well as others involving the pathogenesis, treatment strategies and consequences of apnea in premature infants.
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PMID:Neonatal apnea: what's new? 1878 Mar 39

Retinopathy of prematurity (ROP) is a complex disease of the developing retinal vasculature in premature infants. Clinical manifestations range from mild, usually transient changes of the peripheral retina to severe progressive vasoproliferation, and potentally blinding retinal detachment. With better standards in premature units and with increased survival rate of low gestational age and low birth weight infants the incidence of ROP also increased. The incidence of ROP has been decreasing in developed countries over the past decade, and ROP has become potentially confined to immature neonates with birth weights less than 1000 grams in these countries. Prematurity and retinal immaturity are the major risk factors. Oxygenation, respiratory distress, apnea, bradycardia, hearth disease, infection, hypercarbia, acidosis, anemia, and the need for transfusion are thought by some to be contributory factors. All of the preterm babies with a birth weight under 1500 grams and a gestational age under 32 weeks should be followed for ROP.
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PMID:[Retinopathy of prematurity]. 1940 50


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