Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002063 (alkalosis)
 2,286 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophil adhesion to the vascular endothelium is enhanced during tissue ischemia and/or inflammation, conditions that are associated with tissue acidosis. This study examined the effects of hypercarbic acidosis (10 or 20% CO2) and of hypocarbic alkalosis (0% CO2) on human neutrophil CD18 and human aortic endothelial cell intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin expression quantified by flow cytometry. Acidosis with 20% CO2 for 4 h decreased ICAM-1 to 60.6 +/- 9.7% of control. In contrast, alkalosis with 0% CO2 for 4 h enhanced ICAM-1 expression to 143.8 +/- 10.1% of control. There was no pH dependence of VCAM-1 or E-selectin expression. Tumor necrosis factor-alpha (TNF-alpha; 10 ng/ml) increased endothelial ICAM-1, E-selectin, and VCAM-1; under these conditions, acidosis with 20% CO2 blunted both ICAM-1 and E-selectin surface expression compared with 5% CO2-, TNF-alpha-treated cells. Hypercarbic acidosis with 20% CO2 increased neutrophil CD18 expression and enhanced neutrophil adhesion. This latter effect was inhibited by neutrophil pretreatment with an anti-CD18 monoclonal antibody. In contrast, when only endothelial cells were preincubated with the hypercarbic buffer, neutrophil adhesion diminished to 55.6 +/- 7.8% of control. The results suggest that acidosis generated during tissue ischemia/inflammation may induce CD18-mediated neutrophil adhesion despite a decrease in ICAM-1 expression.
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PMID:pH dependence of neutrophil-endothelial cell adhesion and adhesion molecule expression. 884 27

Biochemical, histological, and physiological evidence suggest strongly that astrocytes may either defend or damage brain tissue, depending on the brain carbohydrate content preceding global ischemia (28,43). This paper will first review the concept of acidosis in ischemia and the possible role of severe, compartmentalized astrocytic acidosis in pan necrosis. Results are then presented demonstrating that astrocytes are also capable of maintaining an alkaline intracellular pH (pHi) during normoglycemic global ischemia. Mechanisms underlying depolarization-dependent astroglial alkalosis are then reviewed. Recent experiments indicate that bicarbonate (HCO3-) transport is a major mechanism by which astroglia not only alkalinize their interior but also acidify the interstitium. Maintenance of alkalosis during normoglycemic ischemia supports the hypothesis that astroglial HCO3- transport might ultimately protect neurons from excitotoxicity in ischemia without infarction (17). Inhibition of astroglial HCO3- transport may be a critical and requisite event, ultimately leading to compartmentalized astroglial acidosis and irreversible injury to all cell types.
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PMID:Astroglial acid-base dynamics in hyperglycemic and normoglycemic global ischemia. 906 37

Magnetic resonance spectroscopy (MRS) allows the noninvasive study of metabolism in vivo. In order to further understand the time course of biochemical changes during cerebral infarction, we performed the MRS study with pathological analysis. The left middle cerebral artery (MCA) was occluded in spontaneously hypertensive male rats (SHR) by the method of Tamura et al. The spectra were obtained from the infarcted hemisphere by placing the surface coils over the left side of the calvarium. 31P and 1H-MRS were performed at 3 hours, 24 hours and 7 days after MCA occlusion. Ischemic lesions caused by the left MCA occlusion extended into the parietal lobe and caudate putamen. After 3 hours of ischemia, vacuolated neurophils and shrunken neurons were observed. At 24 hours, these changes were severe. After 7 days, infiltration of monocytes and capillary hyperplasia were seen, and neurons had disappeared. At the acute stage of ischemia the phosphocreatine/inorganic phosphate (PCr/Pi) peak ratio decreased. After 7 days of ischemia, these changes became obscure. The intracellular pH (pHi) decreased after 3 hours of ischemia and recovered almost to the control level at 24 hours post ischemia. Alkalosis was apparent 7 days after ischemia. This alkalosis might be due to increased permeability of the deteriorated blood brain barrier. Although the lactate level was high 24 hours post ischemia, the pHi was almost normal. The N-acetylaspartate/creatine ratio decreased significantly from the acute stage of stroke. This decrease correlated with pathological changes. The correlation of the magnetic resonance spectra with the histological results may opens aspects for monitoring stroke therapy and a new approach to tissue characterization.
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PMID:[1H and 31P-magnetic resonance spectroscopy of cerebral infarction in rats]. 912 50

In vitro data suggest that low tissue pH reduces, whereas extracellular alkalosis potentiates, cerebral anoxic injury via excitotoxic mechanisms. We tested the hypothesis that in vivo metabolic alkalemia potentiates defects in energy metabolism after global incomplete cerebral ischemia (12 min) and reperfusion (180 min) by an N-methyl-D-aspartate (NMDA) receptor-mediated mechanism. Brain ATP, phosphocreatine, and intracellular pH (pHi) were measured by 31P magnetic resonance spectroscopy in anesthetized dogs treated with 1) preischemic intravenous carbicarb buffer (NaHCO3+Na2CO3, Carb, n = 7); 2) carbicarb infusion plus NMDA receptor antagonist MK-801 (MK-801 + Carb, n = 7); 3) an osmotically equivalent volume of 5% NaCl (NaCl, n = 8); or 4) equivalent volume of 0.9% NaCl (Sal, n = 3). Sagittal sinus pH was raised to 7.82 +/- 0.04 before and 7.65 +/- 0.03 during ischemia in Carb vs. 7.72 +/- 0.01 and 7.60 +/- 0.01 in MK-801+Carb, 7.25 +/- 0.02 and 7.15 +/- 0.03 in NaCl, and 7.31 +/- 0.00 and 7.26 +/- 0.01 in Sal, respectively. Ischemic cerebral blood flow (CBF, radiolabeled microspheres), pHi, and ATP reduction were similar among groups. By 180 min of reperfusion, recovery of ATP was greater in MK-801+Carb (104 +/- 6% of baseline), NaCl (93 +/- 6%), and Sal (94 +/- 6%) than in Carb (47 +/- 6%). Intraischemic pHi was similar among groups, and pHi recovery did not vary among groups despite differences in sagittal sinus pH. In Carb, CBF was restored but with delayed hypoperfusion. We conclude that extracellular alkalosis is deleterious to postischemic CBF and energy metabolism, acting by NMDA receptor-mediated mechanisms.
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PMID:Alkalemia reduces recovery from global cerebral ischemia by NMDA receptor-mediated mechanism. 922 31

To determine the contribution of changes in extracellular osmolarity to ischemic injury, isolated guinea pig hearts were perfused with hyposmotic (220 mosM) or hyperosmotic (380 mosM) buffer. 31P NMR spectroscopy was used to follow changes in intracellular pH (pHi) and energetics. Hyposmotic buffer decreased myocardial developed pressure by 30 +/- 2% and pHi by 0.02 +/- 0.01 unit, whereas hyperosmotic buffer increased myocardial developed pressure by 34 +/- 1% and pHi by 0.14 +/- 0.01 unit. All hearts recovered to control values on restoration of isosmotic (300 mosM) buffer. The hyperosmolar-induced intracellular alkalosis and developed pressure increase were not prevented by inhibition of Na+/H+ exchange with use of 1 microM HOE-642 but were abolished with use of bicarbonate-free buffers. After 20 min of total global ischemia, hearts perfused with hyposmotic buffer showed significantly greater recoveries of developed pressure, phosphocreatine, and ATP than control hearts, but hearts perfused with hyperosmotic buffer did not recover after ischemia. In conclusion, buffer osmolarities between 220 and 380 mosM alter myocardial pHi and developed pressure but are not deleterious during perfusion. However, buffer osmolarity significantly alters the extent of myocardial ischemic injury.
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PMID:Osmotic shock: modulation of contractile function, pHi, and ischemic damage in perfused guinea pig heart. 1019 48

Arachidonic acid (AA) and other nonesterified fatty acids (FAs) have been shown to exert harmful effects during cardiac ischemia. By continuously measuring intracellular pH (pH(i)) changes in neonatal and adult cardiac myocytes, we have found, for the first time, that 10 micromol/L AA induces a substantial intracellular acidosis (0.3 to 0.4 pH units). We have ruled out the possibilities that the AA-induced acidosis is caused by (1) inhibition or stimulation of the pH(i) regulators, (2) protein kinase C activation or the generation of AA metabolites or free radicals, or (3) activation of NADPH oxidase or an inward H(+) current. The AA-induced acidosis fits to a simple diffusion mechanism, as proposed by Kamp and Hamilton (flip-flop model) for artificial phospholipid bilayers. The important properties found in the cardiac myocyte are that (1) the initial rate of acid flux (J(H)) increases with the AA concentration (2 to 50 micromol/L), (2) FAs with a (-)COOH group (eg, AA, oleic acid, and linoleic acid) induce intracellular acidification, but FAs with a (-)COOCH(3) group (eg, AA methyl ester) have little effect on the pH(i), (3) tetradecylamine (FA amine) induces intracellular alkalosis, and, most importantly, (4) both the AA- and tetradecylamine-induced pH(i) changes can be reversed by 0.3% BSA. Because a low concentration of AA (10 micromol/L) can induce a substantial acidosis, the possible involvement of the FA-evoked acidosis in the negative inotropic effect during cardiac ischemia is discussed. The full text of this article is available at http://www. circresaha.org.
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PMID:Possible mechanism(s) of arachidonic acid-induced intracellular acidosis in rat cardiac myocytes. 1067 91

The effect of focal ischemia on tissue pH was studied at various times up to 6 hours after permanent middle cerebral artery occlusion in rats. Tissue pH was imaged by using umbelliferone fluorescence and correlated with cerebral blood flow, ATP content, and recordings of the steady potential. Circumscribed foci of allalosis (pH 7.32+/-0.11) were detected with increasing frequency in penumbral regions having near-to-normal ATP concentrations and cerebral blood flow values between 20% and 40% of control. Both the infarct core, defined by ATP loss and cerebral blood flow values of less than 20% of control, and the inner peri-infarct rim were consistently acidic (pH 6.03+/-0.36 and 6.53+/-0.24, respectively). Treatment with the glutamate antagonist dizocilpine (MK-801) suppressed negative shifts of the steady potential and reduced significantly the occurrence of alkalosis observed in 90% of untreated but only in 44% of treated animals. Penumbral alkalosis appeared to be a time-dependent event occurring 30 to 60 minutes after the passage of peri-infarct depolarizations. The diversity of penumbral pH changes reflects the local disturbance of pH regulation and, possibly, the differential fate of penumbral subareas.
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PMID:Penumbral tissue alkalosis in focal cerebral ischemia: relationship to energy metabolism, blood flow, and steady potential. 1076 60

Mechanical ventilation can worsen morbidity and mortality by causing ventilator-associated lung injury, especially where adverse ventilatory strategies are employed. Adverse strategies commonly involve hyperventilation, which frequently results in hypocapnia. Although hypocapnia is associated with significant lung alterations (e.g., bronchospasm, airway edema), the effects on alveolar-capillary permeability are unknown. We investigated whether hypocapnia could cause lung injury independent of altering ventilatory strategy. We hypothesized that hypocapnia would cause lung injury during prolonged ventilation, and would worsen injury following ischemia-reperfusion. We utilized the isolated buffer-perfused rabbit lung model. Pilot studies assessed a range of levels of hypocapnic alkalosis. Experimental preparations were randomized to control groups (FI(CO(2)) = 0.06) or groups with hypocapnia (FI(CO(2)) = 0.01). Following prolonged ventilation, pulmonary artery pressure, airway pressure, and lung weight were unchanged in the control group but were elevated in the group with hypocapnia; elevation in microvascular permeability was greater in the hypocapnia versus control groups. Injury following ischemia-reperfusion was significantly worse in the hypocapnia versus control groups. In a preliminary series, degree of lung injury was proportional to the degree of hypocapnic alkalosis. We conclude that in the current model (1) hypocapnic alkalosis is directly injurious to the lung and (2) hypocapnic alkalosis potentiates ischemia-reperfusion-induced acute lung injury.
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PMID:Injurious effects of hypocapnic alkalosis in the isolated lung. 1093 60

Functional properties of myofibrils from chronically ischemic canine myocardium were evaluated. Ischemia was produced by tight stenosis of left anterior descending artery (LAD), followed by 40 min acute ischemia with prior preconditioning. Animals of the first group were sacrificed after 8 weeks. In the second group, angioplasty of LAD was performed after 8 weeks of ischemia and animals were kept alive for other 4 weeks. Control animals were sham operated. Activity and kinetic parameters of myofibrillar Ca2+-stimulated Mg2+-ATPase were measured in myofibrils isolated from anterior and posterior parts of all hearts. We did not find any differences in maximal velocity (Vmax), half-maximal activation constant for calcium (K(Ca2+)50) and cooperativity coefficient (n(hill)) of myofibrils from different experimental groups as compared to controls, either at pH 7, pH 6.5 (acidosis) or pH 7.5 (alkalosis). K(Ca2+)50 increased in medium simulated acidosis (12.6-33.5 times) and n(hill) decreased significantly in all groups as compared with values obtained at pH 7. These results indicate that activity and Ca2+-sensitivity of myofibrillar Mg2+-ATPase remain unchanged despite deteriorated heart function 8 weeks after LAD obstruction. Experiments have confirmed that Ca2+-stimulated-ATPase from canine heart myofibrils responded to pH decrease by a decreased sensitivity to Ca2+ and a decreased cooperativity. However, sensitivity of the enzyme to the pH changes is unaltered by 8 weeks of chronic ischemia.
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PMID:Myofibrillar Ca2+-stimulated Mg2+-ATPase from chronically ischemic canine heart. 1216 24

Experimental studies demonstrate an alkaline shift in brain intracellular pH (pH(i)) after hypoxia-ischemia (HI). In infants with neonatal encephalopathy after HI, our aims were to assess (1) brain pH(i) during the first 2 weeks after birth in infants categorized according to magnetic resonance imaging (MRI) during the first 2 weeks after birth and at more than 3 months of age, and neurodevelopmental outcome at 1 year; (2) the relationship between brain pH(i) and lactate/creatine; and (3) duration of alkaline brain pH(i). Seventy-eight term infants with neonatal encephalopathy were studied using MR techniques. One hundred and fifty-one studies were performed throughout the first year including 56 studies of 50 infants during the first 2 weeks after birth. pH(i) was calculated using phosphorus-31 MR spectroscopy and lactate/creatine was measured using proton MRS. The mean (standard deviation [SD]) brain pH(i) during the first 2 weeks after birth in infants with severely abnormal versus normal MRI was 7.24 (SD, 0.17) versus 7.04 (SD, 0.05; p < 0.001); in infants who subsequently developed cerebral atrophy versus those who did not: 7.23 (SD, 0.17) versus 7.06 (SD, 0.06; p < 0.05); in infants who died or had a severe neurodevelopmental impairment versus normal outcome: 7.28 (SD, 0.15) versus 7.11 (SD, 0.09; p < 0.05). Brain alkalosis was associated with increased brain lactate/creatine (p < 0.001). pH(i) remained more alkaline in the severe outcome group up to 20 weeks after birth (p < 0.05).
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PMID:Brain alkaline intracellular pH after neonatal encephalopathy. 1244 26


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