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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In spontaneously breathing, lightly anesthetized rats with chronically implanted epicortical electrodes, tolerance times were measured from onset of progressive hypoxia, anoxia or decapitation, until ultimate apnea and subsequent cessation of brain electrical activities. Arterial and cerebrovenous blood was collected initially and during progressive hypoxia, starting 5 min after intravenous verapamil or NaCl (controls). Verapamil induced significant hyperpnea, arterial alkalosis, slight bradycardia and brain venous acidosis. During progressive hypoxia, hyperpnea persisted and heart rate remained stable for a longer period than in controls. Tolerance times were significantly prolonged. Time courses of arterial PO2 and PCO2 and of cerebrovenous PO2 were hardly influenced. However, arterial alkalosis and brain venous acidosis became highly significant versus control courses. This raised the O2 saturation in arterial and O2 extraction in cerebral venous blood. Sinus sagittalis puncture needle outflow (as a measure of CBF) tended to be below the control rat courses throughout. This led to a higher O2 supply to the brain in verapamil rats only during severe hypoxia. Verapamil did not prolong tolerance times in anoxia or ischemia. It is concluded that the verapamil-induced increase of tolerance to hypoxia is primarily due to the acid-base (Bohr) effects observed in response to hyperpnea and prolonged cerebral metabolic activity.
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PMID:Verapamil enhances brain function tolerance against severe hypoxia without enhancing cerebral blood flow in the rat. 311 71

The response of the kidney to ischemia-induced cellular acidosis was followed over the immediate one hr post-ischemia reflow period. Clearance and extraction experiments as well as measurement of cortical intracellular pH (pHi) were performed on Inactin-anesthetized Sprague-Dawley rats. Arteriovenous concentration differences and para-aminohippurate extraction were obtained by cannulating the left renal vein. Base production was monitored as bicarbonate released into the renal vein and urine; net base production was related to the renal handling of glutamine and ammonia as well as to renal oxygen consumption and pHi. After a 15 min control period, the left renal artery was snared for one-half hr followed by release and four consecutive 15 min reflow periods. During the control period, cortical cell pHi measured by [14C]-5,5-Dimethyl-2,4-Oxazolidinedione distribution was 7.07 +/- 0.08, and Q-O2 was 14.1 +/- 2.2 micromoles/min; neither net glutamine utilization nor net bicarbonate generation occurred. After 30 min of ischemia, renal tissue pH fell to 6.6 +/- 0.15. However, within 45 min of reflow, cortical cell pH returned and exceeded the control value, 7.33 +/- 0.06 vs. 7.15 +/- 0.08. This increase in pHi was associated with a significant rise in cellular metabolic rate, Q-O2 increased to 20.3 +/- 6.4 micromoles/min. Corresponding with cellular alkalosis was a net production of bicarbonate and a net ammonia uptake and glutamine release; urinary acidification was abolished. These results are consistent with a nonexcretory renal metabolic base generating mechanism governing cellular acid base homeostasis following ischemia.
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PMID:Renal acid-base metabolism after ischemia. 372 29

Levels of energy metabolites were measured in forebrain regions in fasted rats subjected to 4-h recirculation after 1 h of either incomplete or complete ischemia. Both models of ischemia were produced by a procedure combining bilateral common carotid artery occlusion, systemic hypotension, and CSF pressure elevation; the degree of intracranial hypertension was varied to produce incomplete and complete ischemia. Levels of brain lactate at the end of ischemia ranged from 16 to 19 mmol/kg in incomplete ischemia and from 11 to 13 mmol/kg in complete ischemia. Energy metabolism recovered evenly in the neocortical and subcortical regions with recirculation after incomplete ischemia. The metabolic recovery in the cerebral cortex after complete ischemia was similar to that observed after incomplete ischemia; however, recovery in the subcortical regions after complete ischemia was less extensive, NADH fluorescence remained high, and there was a fall in total creatine. Intracellular pH in the dorsal thalamus was more alkalotic after complete than incomplete ischemia. Thus, in the absence of profound tissue lactic acidosis, residual CBF during prolonged ischemia helps postischemic restitution of brain energy metabolism in subcortical regions. The pattern of poor recovery in these regions after complete ischemia suggests inadequate reperfusion. The decreased total creatine and the severe tissue alkalosis may be biochemical markers of advanced tissue injury during reflow.
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PMID:Regional brain energy metabolism after complete versus incomplete ischemia in the rat in the absence of severe lactic acidosis. 405 23

The release of gamma-glutamyltransferase from renal tubule cells was studied in situ following 30 minutes of ischemia. The ischemic kidney enzyme level fell 33 percent after 15 minutes of reflow of which only 1.2 percent was recovered in the urine; none was released into the renal vein. At this time the overwhelming majority of the enzyme appears bound to membranes in both the kidney and the urine. In the subsequent 15 minutes renal levels continue to decline while urinary excretion accounts for 5 percent of that disappearing from the kidney. Interestingly the form of the enzyme present in kidney and urine shifts to a soluble form coinciding with cellular alkalosis, urinary alkalinization and a rise in ATP levels. Alkalinization of renal homogenates result in a 2-fold increase in the soluble enzyme form. The results are consonant with the immediate loss of brush border enzyme via uptake into the cell or release into the urine with the former pathway predominating; subsequent appearance of the soluble enzyme appears to reflect intracellular alkaline proteinase activity and exocytosis. The form in which the enzyme is excreted may provide a useful clinical index: membranous reflecting cellular necrosis and soluble reflecting cellular recovery.
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PMID:Gamma-glutamyltransferase release by the post ischemic kidney: multiple forms and cellular pH. 613 82

The induction of alkalosis has been proposed as provocative test of coronary spasm in patients affected by vasospastic angina. We submitted to the test 43 patients, affected by angina with a previous documentation of spontaneous ischemia (19 patients with ST elevation and 24 patients with ST depression at the EKG registered during pain). Twelve patients had normal coronary arteries; in 14 patients a significant stenosis of a single vessel was present; in 15 patients 2 vessels were involved and in 2 a 3-vessel disease was demonstrated. The test induced ischemia in 17 patients (39.6%). The positivity of the test was strictly dependent on the period of time elapsed between the last documented crisis of angina and the provocative test: it induced ischemia in 75% of the patients who underwent the test in the acute phase: on the other hand it was constantly negative in patients who had not complained of anginal pain for more than 6 months. In the screening of patients with chest pain at rest, the test of alkalosis does not seem, therefore, useful as a diagnostic tool.
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PMID:[The alkalinization test in the diagnosis of spontaneous angina]. 673 5

The objective of the present study was to discover whether or not intracellular alkalosis develops in the brain in the recovery period following transient ischemia. Forebrain ischemia of 15-min duration was induced by four-vessel occlusion in rats, with recovery periods of 15, 60, and 180 min. Intracellular pH was derived both by the HCO3- -H2CO3 method and from the creatine kinase equilibrium. The ischemia was associated with energy failure and marked accumulation of lactic acid in the cerebral cortex. Recirculation brought about rapid rephosphorylation of adenine nucleotides and gradual normalization of lactic acid levels. After 15 min of recovery, the HCO3- -H2CO3 method indicated persisting acidosis, but the creatine kinase reaction did not. After 60 min, a shift of pH in the alkaline direction was demonstrated in both methods. This alkalosis had disappeared after 3 h of recovery. It is concluded that resumption of ATP production after ischemia is followed by a rapid rise in intracellular pH, which transiently increases above normal.
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PMID:Intracellular pH in the brain following transient ischemia. 682 11

The influence of prolonged postischemic hyperventilation was studied in the model of global brain ischemia produced by 15 min cardiac arrest in dogs with 8 h recirculation. Histopathological examination of neuronal damage using silver impregnation showed the presence of numerous heavy argyrophylic neurons in the striatum and CA2 hippocampal subfield after 8 h of normoxic reperfusion. In dogs with prolonged 8 h postischemic hyperventilation a reduction in the occurrence of argyrophylic neurons in the striatum and their significant decrease in the hippocampal area were found. Electron microscopic study was performed to characterize the effect of respiratory alkalosis on the ultrastructural changes in neurons and correlate them with the results of silver impregnation. Ultrastructural analysis after the cardiac arrest without recirculation did not reveal the presence of dark neurons within the striatal and hippocampal areas. Neuronal alterations included a decrease in endoplasmic reticulum, mitochondrial swelling and a mild chromatin clumping. After 8 h of normoxic reperfusion many dark, shrinked neurons containing perinuclear clusters of clear vesicles were found. In hyperventilated animals the occurrence of dark neurons with extensive perineuronal edema was substantially reduced in the CA2 subfield. The effect of hyperventilation on postischemic calcium overload is discussed.
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PMID:Effect of prolonged hyperventilation on ischemic injury of neurons after global brain ischemia in the dog. 756 Sep 2

In an attempt to understand the mechanisms by which preischemic plasma glucose (pg) worsens neurologic and neuropathologic outcomes, we investigated the effect of moderate preischemic hyperglycemia (200 mg/dl < mean plasma glucose < 360 mg/dl) on postischemic energy metabolism, tissue intracellular pH (pHi) and tissue free intracellular pMg (= -log[Mg2+]) over a one week period after transient global cerebral ischemia in the rat. In vivo 31P nuclear magnetic resonance spectroscopy was performed prior to and daily up to 1 week (wk) in rats after 12 min of forebrain ischemia, induced by bicarotid occlusion concurrent with systemic hypotension. Preischemic plasma glucose significantly affected 1 wk postischemic survival (p = 0.05, Fisher's exact test). The temporal profile of the brain tissue pHi was significantly different (p < 0.03) between the moderate hyperglycemic (H-1wk, n = 7, mean pg = 266.0 +/- 47.3 mg/dl) and the normoglycemic (N-1wk, n = 8, mean pg = 91.2 +/- 23.7 mg/dl) ischemic animals over 1 wk. Postischemic tissue alkalosis was measured at 24 (p = < 0.006) and 48h (p = 0.001) postischemia in the N-1wk group. A single marginally significant (p = 0.011) mean pHi upshift was measured at 72h postischemia in the H-1wk group. The mean change in pHi at 24h postischemia from the baseline values in moderate hyperglycemic animals that survived only 48h after ischemia (H-48h, n = 6, mean pg = 298.8 +/- 70.1 mg/dl) was significantly lower (p = 0.02) than that of the N-1wk ischemic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of moderate hyperglycemia on the temporal profile of brain tissue intracellular pH and [Mg2+] after global cerebral ischemia in rats. 760 41

We monitored chronically (for 1 week) the effect of the 21-aminosteroid U74006F, a potent lipid peroxidation inhibitor, on the pH profile of the rat brain following transient forebrain ischemia. Eight rats were treated initially with 3 mg/kg i.v. of U74006F 1 min after reperfusion. A second dose of 1.5 mg/kg i.v. was given 60 min after reperfusion. A vehicle group (n = 9) was treated in the same manner, using the same volume of the vehicle solution, 20 mM citric acid, 3 mM sodium citrate, and 8 mM NaCl. Statistically significant interaction between group and time (P = 0.003) was detected for pH. Brain pH of the vehicle treated animals were significantly higher than the U74006F treated group at 24 h (P = 0.009) and 48 h (P = 0.009) of reperfusion. Chronic post-ischemic brain tissue alkalosis at 24 h (pH 7.22 +/- 0.12) and 48 h (pH 7.25 +/- 0.11) post-ischemia, observed among the vehicle treated animals (and untreated animals), was suppressed by treatment with U74006F. These results suggest a coupling between post-ischemic brain tissue alkalosis and free radical induced lipid peroxidation.
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PMID:Post-ischemic brain tissue alkalosis suppressed by U74006F. 843 95

The present experiments were undertaken to study how preischemic hyperglycemia, which is known to exaggerate ischemic damage and to trigger delayed postischemic seizures affects the bioenergetic state and the intracellular pH (pHi) of brain tissue at early (6 h) and late (18 h) recirculation times. To that end, normo- and hyperglycemic rats were subjected to 10 min of forebrain ischemia, and neocortical tissue was frozen in situ for analyses of labile energy metabolites. Animals with preischemic hyperglycemia failed to show a postischemic reduction of the phosphorylation state of the adenine nucleotide pool, or a rise in tissue lactate content, nor did they show a change in tissue redox state. However, the hyperglycemia led to a rise in phosphocreatine (PCr) content after 6 h of recirculation. Calculations of intracellular pH (pHi) from the creatine kinase (CK) equilibrium showed a rise in pHi above normal, a finding which was supported by a limited number of 5,5-dimethyl[2-14C]oxazolidine-2,4-dione (DMO) measurements. The preischemic hyperglycemia also blunted the postischemic rise in tissue glycogen content, which is usually observed in normoglycemic rats. The results thus fail to reveal that the hyperglycemia-triggered, massive exaggeration of ischemic brain damage, which is heralded by generalized seizures after 18-24 h of recirculation, is preceded by mitochondrial dysfunction of a degree which affects the bioenergetic state or the redox potential of the tissue. However, the results suggest that the hyperglycemia enhances and/or prolongs the postischemic alkalosis. It is discussed whether the rise in pH contributes to the mitochondrial dysfunction which subsequently develops.
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PMID:Changes in labile energy metabolites, redox state and intracellular pH in postischemic brain of normo- and hyperglycemic rats. 883 45


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