Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Authors produce a further contribution on metabolic post-hypercapnic alkalosis on the basis of clinical observation of a patient with severe hypercapnia and respiratory failure undergoing intensive care as well as treatment with iron lung (Pulmolife). The improvement of respiratory acid-base umbalance was associated with alteration of electrolytic assessment, especially of the plasmatic chloride ratio. The Authors consider this remark as a starting point for a physiopathological pattern and a more complete analysis of the pathways which generate the metabolic post-hypercapnic alkalosis condition in such patients.
 ...
PMID:[Physiopathological and clinical data on post-hypercapnic metabolic alkalosis. A case of severe hypercapnia treated with drugs and in an "iron lung"]. 43 33

Respiratory complications occur in advanced multiple sclerosis (MS) but may also complicate acute relapses earlier in the disease. We present 19 patients with MS who developed respiratory complications at a mean of 5.9 (range 1-12) yrs after the onset of neurological symptoms. Fourteen patients developed severe respiratory insufficiency presenting with a combination of reduced forced vital capacity (FVC), hypoxaemia or hypercapnia (12 patients) and respiratory arrest (four patients). Two patients presented with apneustic breathing, one with paroxysmal hyperventilation, one with obstructive sleep apnoea and one with bulbar weakness leading to aspiration pneumonia. Respiratory muscle weakness was a major factor in 14 patients (predominantly diaphragm involvement in six), bulbar weakness in seven patients, impaired voluntary control in three and impaired automatic control in three. Twelve patients received mechanical respiratory support of whom seven have subsequently died. The methods of support used were intermittent positive pressure ventilation (nine patients), iron lung (three), cuirass (two) and rocking bed (one). Six patients were maintained on respiratory support until they died after intervals varying from 24 h to 6 yrs (mean 17.7 mths). Five patients received temporary ventilation for between 6 d and 42 d: of these four remain alive at up to 4 yrs and one died after 16 yrs. One patient remains on domiciliary nasal intermittent positive pressure ventilation (IPPV) after 1 yr.
 ...
PMID:Respiratory involvement in multiple sclerosis. 160 78

In newborn pigs, vasodilation in response to hypercapnia is dependent on prostaglandin (PG) H synthase. We investigated the contribution of activated oxygen by-products to hypercapnia-induced PGH synthase-dependent dilation of pial arteries and arterioles in anesthetized newborn pigs. Activated oxygen species were generated on the cerebral surface using xanthine oxidase and hypoxanthine. Catalase, H2O2, and iron or N-(2-mercaptopropionyl)-glycine (MPG) were used to separate effects of superoxide anion and hydroxyl radical. All the activated oxygen species tested caused vasodilation of both arteries and arterioles. Vasodilation to all activated oxygen species was largely reversible with only the hydroxyl radical encouraging combination of xanthine oxidase, hypoxanthine, H2O2, and FeCl3, causing significant dilation 20 min after removal of treatment. Cotreatment with MPG blocked this residual dilation. Neither pretreatment with the extracellular superoxide anion radical scavenger, superoxide dismutase (SOD), the intracellular superoxide anion radical scavenger, Tiron, the H2O2 scavenger, catalase, nor hydroxyl radical scavengers, dimethyl sulfoxide (DMSO) and MPG, altered vasodilation of pial arteries or arterioles in response to hypercapnia. Furthermore, the increase in cerebral prostanoid synthesis in response to hypercapnia was not affected by pretreatment with SOD, Tiron, catalase, DMSO, or MPG. We conclude that the progressively reduced forms of oxygen that would be produced during PGH synthase metabolism of arachidonic acid can dilate pial arteries and arterioles of newborn pigs. However, these activated oxygen species are not responsible for the vasodilation to hypercapnia in the newborn pig, suggesting that eicosanoids cause the dilation.
 ...
PMID:Activated oxygen species do not mediate hypercapnia-induced cerebral vasodilation in newborn pigs. 187 61

We superimposed extreme hypercapnia (arterial Pco2 400-450 mmHg) immediately before and during incomplete cerebral ischemia to distinguish the role of intracellular pH (pHi) and bicarbonate [( HCO3-]i) in postischemic metabolic and electrophysiological recovery. Incomplete global ischemia was produced in seven anesthetized dogs by 30 min of intracranial hypertension followed by 4 h of reperfusion. ATP, phosphocreatine (PCr), and pHi were measured with 31P magnetic resonance spectroscopy, and [HCO3-]i was calculated from the Henderson-Hasselbalch equation using the measured pHi and sagittal sinus Pco2. Cerebral blood flow was reduced to 7 +/- 1 ml.min-1.100 g-1 (+/- SE) during ischemia with extreme hypercapnia, and pHi decreased to 5.72 +/- 0.09. During normocapnic reperfusion, pHi rapidly returned to near baseline values by 14 min. [HCO3-]i fell from 12.1 +/- 0.9 to 6.0 +/- 1.2 mM by the midpoint of ischemia and recovered by 30 min of reperfusion. ATP, PCr, and O2 consumption also recovered rapidly and completely. Somatosensory-evoked potentials (SEP) recovered to 43 +/- 10% of control amplitude. These results are in marked contrast to the poor metabolic and SEP recovery previously observed in hyperglycemic dogs in which pHi decreased to the same range as with hypercapnic ischemia, but in which [HCO3-]i was much lower (1.1 +/- 0.5 mM). Therefore, [HCO3-]i depletion during hyperglycemic ischemia may be a more important factor in recovery than end-ischemic pHi per se. We speculate that higher [HCO3-]i may improve glial cell buffering capacity or decrease iron availability for hydroxyl radical production.
 ...
PMID:Bicarbonate conservation during incomplete cerebral ischemia with superimposed hypercapnia. 190 5

Effects of topical application of hydrogen peroxide (H2O2) on pial arteriolar diameter and cerebral prostanoid synthesis were examined in newborn pigs. H2O2 (10 mM) caused initial constriction during the 1st min, followed by prolonged (20 min) dilation that was reversed on removal of the H2O2 in piglets treated with deferoxamine. H2O2 also caused an increase in cortical periarachnoid 6-ketoprostaglandin F1 alpha, thromboxane (TX) B2, and prostaglandin (PG) E2. Indomethacin pretreatment or coadministration of SQ 29548 (PGH2/TXA2 receptor antagonist) with H2O2 blocked the constriction due to H2O2 but did not alter the dilation. The constriction, the dilation, and the increased prostanoids caused by H2O2 were not affected by topical and systemic deferoxamine (an iron chelator) or simultaneous application of FeSO4 and FeCl3. Neither prior treatment with H2O2 nor with H2O2 plus FeSO4 and FeCl3 altered pial arteriolar dilation in response to hypercapnia. Therefore the initial constriction caused by H2O2 appears to result from stimulation of prostanoid synthesis and activation of PGH2/TXA2 receptors, whereas the dilation is not caused by prostanoids. H2O2 alone does not produce detectable residual alteration of pial arteriolar responsiveness or cerebral prostanoid synthesis.
 ...
PMID:H2O2 effects on cerebral prostanoids and pial arteriolar diameter in piglets. 233 73

The influence of lactic acidosis and of extreme hypercapnia on free radical generation and lipid peroxidation in brain tissues was studied. Cortical homogenates were prepared from the rat brain in a bicarbonate buffer and incubated for 60 min. Lipid peroxidation was evaluated by measurements of thiobarbituric acid reactive (TBAR) material and alpha-tocopherol analysis. The pH during incubations were decreased to 6.10-6.20 by either lactic acid administration or equilibration with 60% CO2 gas in paired experiments. In homogenates treated with lactic acid there was a 20-fold increase in TBAR material and the alpha-tocopherol concentration decreased to approximately 60% of control. There was only a 10-fold increase in TBAR material and no change in alpha-tocopherol concentration if acidosis was induced by CO2. These differences between lactic acidosis and hypercapnic acidosis were statistically highly significant. The results indicate that lactic acidosis has a more pronounced effect in augmenting free radical generation in brain tissues than acidosis due to an increase in CO2 tension. It is suggested that this effect of lactic acid is mediated by increased dissociation of catalytic iron from proteins of the transferrin type.
 ...
PMID:Enhancement of iron-catalyzed free radical formation by acidosis in brain homogenates: differences in effect by lactic acid and CO2. 249 27

Interest has been increasing in providing ventilatory support in the home for patients with chronic respiratory failure, mainly with the use of positive pressure ventilation via a chronic tracheostomy. However, body ventilators that assist ventilation by applying intermittent negative or positive pressure to the thorax, abdomen, or airway without requiring an artificial airway, can offer distinct advantages for selected patients over systems requiring a permanent airway. These ventilators include the iron lung, portable lung (Portalung), pneumowrap, chest cuirass, pneumobelt, rocking bed, and positive pressure provided via a face or nose mask. They have successfully stabilized or reversed chronic hypercarbia when used intermittently in patients with slowly progressive chronic respiratory failure due to certain neuromuscular diseases and kyphoscoliosis. How they achieve this stabilization has not been clarified, but reversal of chronic respiratory muscle fatigue following periodic rest probably contributes. These ventilators are generally less effective than positive pressure ventilation through a tracheostomy and should be reserved for patients with relatively stable chronic respiratory failure and intact upper airways. However, they have the advantages of simpler operation and less expense, and they allow maintenance of a normal airway.
 ...
PMID:Clinical applications of body ventilators. 353 43

The isolated hepatocyte suspension was evaluated as an experimental procedure for investigating liver iron metabolism. Following prelabelling in vivo with transferrin-59Fe, isolated hepatocytes released radioactive iron in vitro by a temperature dependent process, without change in cell viability. Iron mobilization was increased by serum, apotransferrin and a range of iron chelators, of which the most effective were citrate, desferrioxamine and the ionophore A 23187. The rate of iron release was inversely related to oxygen levels, indicating that a ferric-ferrous reduction was involved in iron mobilization. The uncoupler TTFB, DTPA, and hypercapnia caused a reduction in iron release, but the metabolites cysteine, NADH and ascorbic acid had no effect. It was concluded that isolated hepatocytes are a useful experimental model for studying iron metabolism and for further evaluation of iron chelators.
 ...
PMID:Iron release from isolated hepatocytes. 721 73

The present article is concerned with mechanisms which are responsible for the exaggerated brain damage observed in hyperglycemic animals subjected to transient global or forebrain ischemia. Since hyperglycemia enchances the production of lactate plus H+ during ischemia, it seems likely that aggravation of damage is due to exaggerated intra- and extracellular acidosis. This contention is supported by results showing a detrimental effect of extreme hypercapnia in normoglycemic rats subjected to transient ischemia or to hypoglycemic coma. Enhanced acidosis may exaggerate ischemic damage by one of three mechanisms: (i) accelerating free radical production via H(+)-dependent reactions, some of which are catalyzed by iron released from protein bindings by a lowering of pH, (ii) by perturbing the intracellular signal transduction pathway, leading to changes in gene expression or protein synthesis, or (iii) by activating endonucleases which cause DNA fragmentation. While activation of endonucleases must affect the nucleus, the targets of free radical attack are not known. Microvessels are considered likely targets of such attack in sustained ischemia and in trauma; however, enhanced acidosis is not known to aggravate microvascular dysfunction, or to induce inflammatory responses at the endothelial-blood interface. A more likely target is the mitochondrion. Thus, if the ischemia is of long duration (30 min) hyperglycemia triggers rapidly developing mitochondrial failure. It is speculated that this is because free radicals damage components of the respiratory chain, leading to a secondary deterioration of oxidative phosphorylation.
 ...
PMID:Molecular mechanisms of acidosis-mediated damage. 878 Jul 90

Although previous results have shown unequivocally that pre-ischaemic hyperglycaemia aggravates brain damage due to transient ischaemia, several questions have remained unanswered. First, is the effect of hyperglycaemia due to a further fall in intra- and extracellular pH? Second, is aggravation of damage a step function of a continuous function of plasma glucose concentration or of pH? Third, which are the mechanisms responsible for aggravation of damage, notably for the transformation of selective neuronal damage to infarction, for oedema development, and for post-ischaemic seizures? Recent results have provided new information on all of these issues. Thus, normoglycaemic animals with superimposed hypercapnia showed a similar, albeit not identical, aggravation of ischaemic damage, suggesting that acidosis is one major mediator. Furthermore, experiments with graded increase in plasma glucose concentration revealed a threshold effect at values of 10-12 mM, while microelectrode measurements showed a narrow extracellular pH range (6.4-6.5) for post-ischaemic seizure development. These results suggest that aggravation of damage due to excessive acidosis is due to mechanisms with a steep pH dependence. Finally, results are now at hand suggesting that the effect of acidosis is not mediated by a further perturbation of cell calcium metabolism. The more likely mediators are free radicals. Thus, acidosis is known to enhance iron-catalysed production of reactive oxygen species, probably by releasing iron from its bindings to transferrin, ferritin and other proteins.
 ...
PMID:Role of hyperglycaemia-related acidosis in ischaemic brain damage. 942 66


1 2 3 Next >>