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)

1. Acute lung injury (ALI) as a result of sepsis is a major cause of mortality. Certain anaesthetic agents have been reported to suppress pro-inflammatory cytokines and inducible nitric oxide (NO) synthase (iNOS) activities. We investigated the effects of pentobarbital on ALI and organ functions after the administration of endotoxin. 2. Intravenous (i.v.) pentobarbital (20 or 40 mg/kg) was administered 5 min after lipopolysaccharide (LPS; 10 or 30 mg/kg via i.v. infusion). To avoid hypoxia and/or hypercapnia following anaesthesia, we installed a special chamber connected to a rodent ventilator to provide ventilation with 95% oxygen content and 5% nitrogen. The animal was kept at eucapnic conditions (arterial PCO2 at an average of 38 +/- 2 mmHg). 3. We monitored the arterial pressure (AP) and heart rate (HR). Acute lung injury was evaluated by lung weight changes, protein concentration in bronchoalveolar lavage, and Evans blue leakage. Plasma nitrate/nitrite, methyl guanidine and biochemical factors were determined. Pathological and immunofluorescent examinations were performed to observe the lung changes and to determine the activities of pro-inflammatory cytokines, nitrotyrosine and iNOS. 4. Lipopolysaccharide caused dose-dependent systemic hypotension with an increase in the extent of ALI. The lung pathology included oedema and inflammatory cell infiltration. Accompanying the ALI, LPS elevated plasma nitrate/nitrite, methyl guanidine, blood urea nitrogen, lactic dehydrogenase, creatinine phosphokinase, glutamic transaminase and amylase. The lung tissue content of tumour necrosis factor-alpha, interleukin-lbeta, iNOS and nitrotyrosine was increased following LPS administration. These changes were abrogated by pentobarbital anaesthesia. 5. Our results indicated that pentobarbital anaesthesia significantly augmented the LPS-induced systemic hypotension. However, it attenuated the LPS-induced ALI and organ dysfunctions. This agent also improved the survival rate following LPS at high and low doses. This mechanism may be related to the inhibitory effects on the increases in the production or activity of NO, free radicals, pro-inflammatory cytokines, nitrotyrosine and iNOS.
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PMID:Endotoxin-induced acute lung injury and organ dysfunction are attenuated by pentobarbital anaesthesia. 1743 19

Acid aspiration or intrapulmonary instillation of gastric particles causes lung inflammation leading to acute lung injury (ALI). Hypercapnia exerts different effects on ALI caused by various insults. The effects of hypercapnia on lung inflammation and injury due to acid aspiration are yet to be determined. The present study was designed to investigate the involvement of inducible nitric oxide synthase (iNOS) and other mediators in acid-aspiration-induced ALI. We also sought to evaluate the effects of hypercapnia on the lung and associated changes induced by acid aspiration. We used Spague-Dawley rats anesthetized with intraperitioneal pentobarbital (40 mg/kg). Gastric acid particles were prepared from the stomach contents of rats at necropsy. The rats were randomly assigned to receive intratracheal instillation of physiological saline solution (PSS) at pH 7.24 (Control group), PSS at pH 1.25 (Low pH, LPH group), gastric particles (GP group), and GP with low pH PSS (GPLPH group). There were 10 rats in each group. The animals were observed for 6 hrs. To evaluate the effects of hypercapnia, we carried out two series of experiments: one under normocapnia and the other under hypercapnia with alteration of CO2 fraction in inspired air. Arterial pressure (AP) was monitored from the femoral arterial catheter. Heart rate was obtained from AP traicing. We determined the blood gases and acid-base status. Lung weight to body weight (LW/BW) ratio, LW gain (LWG), protein concentration in bronchoalveolar lavage (PCBAL) and leakage of Evans blue dye tracer were measured. Plasma nitrate/nitrite, methyl guanidine (MG), myeloperoxidase (MPO), phospholipase A2 (PLA2), proinflammatory cytokines were assessed. Histopathological examination of the lung tissue was performed. We employed reverse-transcriptase polymerase chain reaction to detect the expression of iNOS mRNA. GP and GPLPH caused hypotension, decreases in PaO2, pH and SaO2, and an increase in PaCO2. The insults also elevated LW/BW, LWG, PCBAL and dye leakage, plasma nitrate/nitrite, MG, MPO, PLA2, tumor necrosis factor(alpha), interleukin-beta and interleukin-6. The lung pathology was characterized by alveolar edema and hemorrhage with inflammatory cells infiltration. Assessment of lung injury score revealed that GP and GPLPH caused ALI. Furthermore, hypercapnia significantly enhanced ALI and associated changes following LPH, GP and GPLPH. Intratracheal instillation of GP in normal or low pH PSS causes ALI accompanied with biochemical changes. The release of nitric oxide via iNOS isoform is detrimental to the lung. Hypercapnia tended to enhance ALI and associated changes induced by gastric acid instillation.
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PMID:Enhancement effects of hypercapnia on the acute lung injury caused by acid aspiration. 1977 97

Although respiratory complications significantly contribute to morbidity/mortality in advanced myelin disorders, little is known concerning mechanisms whereby dysmyelination impairs ventilation, or how patients compensate (i.e. plasticity). To establish a model for studies concerning mechanisms of ventilatory impairment/compensation, we tested the hypotheses that respiratory function progressively declines in a model of CNS dysmyelination, the Long Evans shaker rat (les). The observed impairment is associated with abnormal inspiratory neural output. Minimal myelin staining was found throughout the CNS of les rats, including the brainstem and cervical bulbospinal tracts. Ventilation (via whole-body plethysmography) and phrenic motor output were assessed in les and wild-type (WT) rats during baseline, hypoxia (11% O(2)) and hypercapnia (7% CO(2)). Hypercapnic ventilatory responses were similar in young adult les and WT rats (2 months old); in hypoxia, rats exhibited seizure-like activity with sustained apneas. However, 5-6 month old les rats exhibited decreased breathing frequencies, mean inspiratory flow (V(T)/T(I)) and ventilation (V (E)) during baseline and hypercapnia. Although phrenic motor output exhibited normal burst frequency and amplitude in 5-6 month old les rats, intra-burst activity was abnormal. In WT rats, phrenic activity was progressive and augmenting; in les rats, phrenic activity was decrementing with asynchronized, multipeaked activity. Thus, although ventilatory capacity is maintained in young, dysmyelinated rats, ventilatory impairment develops with age, possibly through discoordination in respiratory motor output. This study is the first reporting age-related breathing abnormalities in a rodent dysmyelination model, and provides the foundation for mechanistic studies of respiratory insufficiency and therapeutic interventions.
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PMID:Ventilatory impairment in the dysmyelinated Long Evans shaker rat. 2054 92


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