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Query: UMLS:C0085383 (hypocapnia)
 1,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of hypoxemia on the brain content of several organic acids and NH+4, AND ITS RELATIONship to the accompanying hypocapnia was studied in unanesthetized rats subjected to hypoxemia for periods ranging between 2 hours and 7 days. Under acute conditions, 'mild' hypoxemia (FO2 = 6--7%), these increases were greater and accompanied by increased gamma-aminobutyric acid (GABA) and decreased glutamic and aspartic acid levels; glutamine and NH+4 remained normal. When hypocapnia was prevented, 'severe' hypoxemia induced only a rise in GABA and slight elevations in lactic and alpha-ketoglutaric acid. During prolonged severe hypoxemia, the effects on the brain amino acids were maintained throughout, indicating that they are independent from the intracerebral pH which should progressively normalize. The effect on lactic acid gradually disappeared. The results show that during hypocapnic hypoxemia the rise in brain GABA is hypoxemia dependent, the decrease in glutamic and aspartic acid is hypocapnia dependent and the increase in lactic acid is in a large way alkalosis dependent.
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PMID:Brain amino acids in conscious rats in chronic normocapnic and hypocapnic hypoxemia. 92

Hyperammonemia increases brain glutamine levels, causes astrocytic swelling, and depresses cerebral blood flow (CBF) responsivity to CO2. Methionine sulfoximine (MSO) inhibition of glutamine synthetase activity, known to be enriched in astrocytes, prevents ammonia-induced increases in brain glutamine and water content. We tested the hypothesis that inhibition of glutamine accumulation restores CBF responsivity to CO2 during acute hyperammonemia. Pentobarbital-anesthetized rats treated with either vehicle or MSO (150 mg/kg i.p.) received a 6-hour intravenous infusion of either sodium or ammonium acetate. With subsequent induction of hypercapnia, CBF increased from 113 +/- 14 (mean +/- SEM) to 194 +/- 9 ml/min per 100 g in control rats but was unchanged from 107 +/- 13 to 79 +/- 10 ml/min per 100 g in hyperammonemic rats. Treatment with MSO in hyperammonemic rats restored the CBF response to hypercapnia (from 73 +/- 8 to 141 +/- 14 ml/min per 100 g). With induction of hypocapnia, CBF decreased from 114 +/- 11 to 88 +/- 11 ml/min per 100 g in control rats but increased from 112 +/- 13 to 142 +/- 19 ml/min per 100 g in hyperammonemic rats. Treatment with MSO in hyperammonemic rats did not fully restore the response to hypocapnia but prevented the paradoxical increase in CBF (from 80 +/- 8 to 80 +/- 8 ml/min per 100 g). In control rats, MSO did not affect CO2 responsivity. Treatment with MSO prevented ammonia-induced increases in intracranial pressure. Hyposmotic-induced increases in brain water content and intracranial pressure attenuated the CBF response to hypercapnia but, unlike hyperammonemia, did not attenuate the response to hypocapnia. In contrast to hypercapnia, vasodilation in response to arterial hypotension was intact in hyperammonemic rats. We conclude that the grossly abnormal CBF responsivity to CO2 alterations during hyperammonemia is linked to glutamine accumulation rather than ammonia per se. Cerebral edema secondary to glutamine accumulation may contribute in part to abnormal CBF responses, although other aspects of astrocyte dysfunction are likely to be important.
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PMID:Restoration of cerebrovascular CO2 responsivity by glutamine synthesis inhibition in hyperammonemic rats. 139 82

Acute respiratory alkalosis (blood pH, 7.60; arterial PCO2, 15 mmHg (1 mmHg = 133.322 Pa); plasma bicarbonate, 14 mM) was induced in nine anesthetized dogs by increasing their respiratory rate and depth. Renal glutamine extraction and ammonia production expressed per 100 mL of glomerular filtration rate did not change during acute hypocapnia, whereas arterial glutamine concentration decreased significantly from 0.47 to 0.36 mM. Hypocapnia did not change plasma potassium concentration and its urinary excretion. Acute hypocapnia increased lactate extraction and pyruvate production, whereas citrate extraction and glutamate and alanine production did not change. Citraturia remained minimal. Renal cortical glutamine concentration fell from 0.64 to 0.38 mM during hypocapnia while alpha-ketoglutarate, glutamate, malate, oxaloacetate, and citrate did not change. Lactate concentration rose from 1.1 to 2.0 mM. Glutamine concentration in the liver and muscle decreased following acute hypocapnia. Our data are compatible with the hypothesis that an acute respiratory alkalosis might not result in any change in the hydrogen ion concentration and (or) gradient between the mitochondrial matrix and the cytosol. Consequently, renal glutamine extraction and ammonia production are not reduced, renal cortical concentrations of relevant metabolites in the ammoniagenic pathway are not changed, and renal handling of citrate remains unaffected.
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PMID:Renal metabolism and ammoniagenesis during acute respiratory alkalosis in the dog. 649 24

Ammonia intoxication, which results in astrocytic edema and glutamine accumulation, blocks cerebral vasodilation during hypercapnia but not during hypoxia. Ammonia's effect on blood flow during hypocapnia is unclear, with some brain regions showing a paradoxical increase in flow. Here, we studied the responses to hypocapnia of pial arterioles not surrounded by astrocytic end feet to avoid mechanical compression by local edema. Blood flow was measured by microspheres in pentobarbital sodium-anesthetized rats equipped with closed cranial windows that permitted intravital microscopy. The normal pial arterial constriction in hypocapnia (12 +/- 1%; mean +/- SE) was blocked (2 +/- 1%) during a 6-h intravenous infusion of ammonium acetate, with some regions (cerebrum, midbrain) showing increased flow during hypocapnia. After pretreatment with methionine sulfoximine (MSO), which inhibits glutamine synthesis, the normal hypocapnic constrictor response was retained in pial arterioles (11 +/- 2%) during hyperammonemia. The increase in the calculated cerebrovascular resistance also was retained. An analog of MSO that does not block glutamine synthesis (buthionine sulfoximine) was ineffective in maintaining hypocapnic reactivity. In a sodium acetate-treated control group, MSO did not alter the pial arteriolar response. Normal vasoconstrictive ability was shown during ammonium infusion in response to U-46619, a thromboxane analog. We conclude that the inhibition of hypocapnic responsivity induced by ammonium is not due to paralysis of the pial arteriolar smooth muscle or to vascular compression by swollen astrocytes but is in some way due to glutamine metabolically produced from the ammonium.
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PMID:Preserved hypocapnic pial arteriolar constriction during hyperammonemia by glutamine synthetase inhibition. 995 Aug 45

Patients with FHF have a high risk of cerebral edema and intracranial hypertension. The pathophysiological background for this phenomenon is not completely settled, but alteration in CBF as well as cerebral metabolism seems to be of importance. Mechanical hyperventilation has a prompt effect on intracranial pressure. This effect is assumed to be caused by the hypocapnia induced alkalosis which produces vasoconstriction and thereby a decrease in CBF and cerebral blood volume. It has been stated that hyperventilation may be harmful to patients with FHF, but only few studies have addressed the effect of hyperventilation upon cerebral metabolism. In the present clinical studies we evaluated the effect of short-term mechanical hyperventilation upon cerebral circulation and metabolism in patients with FHF. Although global CBF was reduced in patients with FHF it tightly matched the cerebral oxidative requirements. Already in the early phase of FHF there was a prominent cerebral efflux of glutamine that could not be accounted for by cerebral ammonia uptake. Moderate hyperventilation reduced global CBF without compromising cerebral oxidative metabolism. In addition, moderate hyperventilation restored cerebral autoregulation in most patients with FHF, and normalised the cerebral nitrogen balance during short-term interventions. Studies of global and regional cerebral carbon dioxide reactivity showed normal global as well as regional cerebral carbon dioxide reactivity in almost all patients with FHF. However, cerebral perfusion in frontal brain regions as well as basal ganglia is low in FHF as compared to healthy subjects, which may make these regions at risk of hypoperfusion during pronounced hyperventilation. It is concluded that moderate short-term hyperventilation does not compromise cerebral oxidative metabolism. Recommendation of its prolonged use in FHF awaits further studies. Furthermore, the data of this thesis demonstrates that alterations in cerebral glutamine and ammonia metabolism precedes increases of CBF, which seems to be a phenomenon that takes place later during the disease course, i.e., immediately before intracranial pressure is rising.
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PMID:The effect of hyperventilation upon cerebral blood flow and metabolism in patients with fulminant hepatic failure. 1752 26