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

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 hyperammonemia at normal arterial pH causes selective increases in midbrain blood flow in dogs. Unexpectedly, further increases occur with hypocapnia. We investigated whether metabolic acidemia and alkalemia modulate the distribution of ammonium across the blood-brain barrier and if, in turn, midbrain blood flow is effectively modulated. In dogs anesthetized with pentobarbital sodium, hyperammonemia (approximately 940 microM) was produced by a 210-min infusion of ammonium acetate. Concurrent infusion of NaHCO3 increased arterial pH to 7.53 +/- 0.02 (SE), whereas HCl infusion decreased pH to 7.11 +/- 0.01. Normocapnia was maintained. Cerebrospinal fluid [HCO3-] increased 5 mM with alkalemia (one-half of the increase in blood) and was unchanged with acidemia. Thus cerebrospinal fluid [H+]/blood [H+] was greater with alkalemia than acidemia. The corresponding ratio for ammonium was likewise greater with alkalemia (0.70 +/- 0.06) than acidemia (0.44 +/- 0.08). Microsphere-determined blood flow to midbrain more than doubled in the alkalemic group but was unchanged in the acidemic group. No other region along the neuraxis or in cerebrum showed increased blood flow in either hyperammonemic group. Alkalemia without hyperammonemia did not increase midbrain blood flow. Thus metabolic acidemia-alkalemia significantly alters ammonium partitioning into cerebrospinal fluid, and this alteration is sufficiently great to exert a specific physiological effect manifested by changes in midbrain blood flow.
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PMID:Arterial pH modulation of regional cerebral blood flow during hyperammonemia in dogs. 197 74

Studies of acutely induced hyperammonemia and chronic hyperammonemia associated with liver dysfunction suggest that cerebral blood flow (CBF) and O2 consumption (CMRO2) become uncoupled and that CMRo2 may depend on arterial CO2 tension (PaCO2). We examined CBF (radiolabeled microspheres) and CMRO2 during hypercapnia (PaCO2 congruent to 74 Torr) and hypocapnia (PaCO2 congruent to 21 Torr) both before and during intravenous ammonium acetate infusion in pentobarbital-anesthetized dogs. Continuous infusion over 120 min produced stable increases of arterial ammonia levels (1,400 mumol/l) by 30 min, whereas CBF, CMRO2, and O2 extraction (measured at sagittal sinus) remained unchanged when PaCO2 was held constant (congruent to 35 Torr). Acute hyperammonemia attenuated the increase in CBF during hypercapnia by 44% and abolished the decrease in CBF during hypercapnia. Regional blood flow to pons and midbrain increased under normocapnic conditions, and midbrain blood flow increased further during hypocapnia. Sodium acetate infusion did not affect CBF responses to CO2. Thus we failed to observe an uncoupling of global CBF and CMRO2 during normocapnic hyperammonemia, or an interaction of CO2 and ammonia on CMRO2, although the increased pons and midbrain blood flow may reflect regional effects of ammonia on reticular activating system metabolism. On the basis of the literature, we suggest that the attenuated hypercapnic CBF response may arise from impaired glial regulation of extracellular potassium and bicarbonate concentrations and that lactic acid production, enhanced by combined alkalosis and hyperammonemia, may contribute to the abolition of hypocapnic vasoconstriction.
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PMID:Interaction of CO2 and ammonia on cerebral blood flow and O2 consumption in dogs. 392 Sep 20

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

We investigated ventillatory responses to a plasma alkaloids and hypocapnia,a nd the basis for the ventilatory response to sodium bicarbonate (NaHCO3) infusion in rainbow trout. Plasma alkalosis and hypocapnia created by infusion of sodium hydroxide (NaOH) did not cause hypoventilation, whereas infusion of hydrochloric acid (HCl) caused vigorous hyperventilation, associated with an acidosis, a reduction in blood O2 content (CaO 2) and a release of circulating catecholamines. Infusion of NaHCO3 stimulated ventilation and caused an increase in plasma pH, total carbon dioxide content (CaCO 2) and catecholamine levels, and a reduction in oxygen tension (PaO 2). Infusion of ammonium bicarbonate (NH 4HCO3) caused hyperventilation and was associated with an increase in CaCO 2 and plasma total ammonia (Camm) and ammonia gas (NH3) concentration. Infusion of sodium chloride (NaClI) and Cortland's saline had no effect on ventilation. The results indicate that trout do not exhibit the ventilatory sensitivity to pH seen in terrestrial vertebrates. Ventilatory responses to NaHCO3 appear to have been a result of reductions in PaO 2, a release of catecholamines and an increase in CaCO 2 whereas responses to NH4HCO3 appear to have been a result of increases in CaCO 2 and Camm.
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PMID:Effects of changes in plasma pH, CO2 and ammonia on ventilation in trout. 2421 51