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

The presence of lactic acidosis in the cerebrospinal fluid of patients suffering brain injury as the result of trauma, subarachnoid hemorrhage, neoplasia, or ischemia has been well documented. The authors theorized that this acidosis becomes harmful in itself, and that treatment with an alkalinizing agent (tris(hydroxymethyl)aminomethane: tromethamine) capable of penetrating the blood-brain barrier would be efficacious. Fifteen pairs of mongrel cats were subjected to a 2.85-atmosphere fluid-percussion injury (LD80), and were supported by respirators for up to 72 hours prior to being placed in cages for an additional 4 days of observation. Experimental cats underwent continuous infusion of tromethamine (begun 10 minutes after injury); control animals were infused with an equal volume of lactated Ringer's solution. Twenty percent of the control group survived until sacrificed on Day 7 post-injury. Survival in the tromethamine group was 60% (p less than 0.05), and morbidity also appeared to be reduced in the treated cats. Intracranial pressure (ICP) in treated cats was 60% (p less than 0.05) of that in the control cats after respirator support for 3 days. Tromethamine infusion was associated with improved survival, decreased morbidity, and decreased ICP when compared with results in control animals. The literature with regard to central nervous system acidosis has been reviewed in an attempt to clarify and define this problem.
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PMID:Experimental brain injury: successful therapy with the weak base, tromethamine. With an overview of CNS acidosis. 671 65

Studies were done on rats to determine whether thiopental loading after complete, transient, global brain ischemia causes more rapid postischemic normalization of brain tissue pH. Fifteen halothane-anesthetized rats were subjected to 16 min of complete global brain ischemia by a combination of systemic arterial hypotension (40 torr) and a high pressure (1500 torr) neck cuff. Brain tissue pH was continuously monitored for up to 2 hour postischemia with microelectrodes (tip diameters of one to two micrometers) inserted about 500 micrometers into the parietal cortex. During ischemia, brain pH fell rapidly within the first 5 min from 7.0 to 6.2 and changed little thereafter. With restoration of arterial pressure and deflation of the neck cuff, pH did not immediately begin to rise back towards normal. Instead, after a few minutes, it transiently fell to even lower values before beginning to increase indicating increased tissue lactic acidosis when the brain is resaturated with glucose upon reperfusion. Beginning at 5 min postischemia, 7 of the 15 rats were infused with thiopental (90 mg/kg, IV over 60 min). At 30 min postischemia, brain tissue pH was similar in both groups and by 60 min, back to preischemic values. We conclude that thiopental loading postischemia does not improve normalization of brain pH. The transient decrease in brain pH with reperfusion is discussed.
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PMID:Brain tissue pH after global brain ischemia and barbiturate loading in rats. 678 85

Glucose, lactate, pyruvate and adenosine triphosphate (ATP) concentrations in the supratentorial brain tissue frozen in situ were measured one hour after bilateral carotid occlusion in spontaneously hypertensive rats, of which blood glucose levels were varied by intraperitoneally injected insulin (hypoglycemia), saline (normoglycemia) and 50% glucose (hyperglycemia). Cerebral glucose concentrations as well as blood glucose levels were significantly increased in hyperglycemic animals, and decreased in hypoglycemic ones. Cerebral lactate, and lactate/pyruvate ratio at one-hour ischemia tended to increase in hyperglycemic animals comparing with those in normoglycemic ones, although cerebral ATP levels were slightly higher in the former. In hypoglycemic animals with one-hour ischemia, cerebral lactate was less increased but ATP was significantly reduced. It has been reported that hyperglycemia has vulnerable effects on brain metabolism of complete cerebral ischemia, presumably due to hyperglycemia-induced lactic acidosis of the brain. In incomplete cerebral ischemia as demonstrated in the present study, however, ATP concentrations remained at slightly higher level, despite tendency to more increase in lactate in hyperglycemic animals, indicating that high blood glucose level might be beneficial, rather than vulnerable, to incomplete cerebral ischemia. On the other hand, hypoglycemia causes more severe impairment of the brain energy metabolism because of an insufficient supply of substrates to the brain.
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PMID:[Effects of hypo- or hyperglycemia on brain metabolism in experimental cerebral ischemia]. 684 11

Severe incomplete cerebral ischemia of 30 min duration with CBF below 5% of normal was induced in rats by clamping both carotids and lowering BP. One group of rats were fasting (f-rats), while the other was infused with glucose before induction of the ischemia (g-rats). In f-rats the lactate accumulating in the cerebral cortex was about 15 mumol . g-1, whereas in g-rats it rose to about 35 mumol . g-1. In f-rats considerable recovery of the energy state and electrical activity occurred during recirculation, whereas in g-rats the energy failure persisted with no electrical activity reappearing. In f-rats the structural alterations were of minor severity, but in g-rats extensive progressive tissue damage was seen. The data indicate that the degree of tissue lactic acidosis has pronounced effects on the development of irreversible ischemic nerve cells injury.
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PMID:The role of lactic acidosis in the ischemic nerve cell injury. 693 34

Biochemical factors of potential importance for the development of irreversible brain cell damage in reversible ischemia may, at least theoretically, not only involve anaerobic events but also oxidative reactions. If so, such reactions should be expected to occur either if oxygen delivery to the tissue during ischemia is not totally abolished, i.e. as in incomplete ischemia, or during the recirculation phase. Several investigations have shown that pronounced incomplete brain ischemia is more deleterious than complete ischemia. The persistence of some circulation in the former situation may a) allow oxidative reactions to continue at a slow rate b) lead to excessive tissue lactic acidosis by continued supply of substrate for anaerobic glycolysis. Our studies concerning brain tissue concentrations of reduced and oxidized glutathione, fatty acids and phospholipids in reversible, pronounced, incomplete and complete ischemia fail to support the hypothesis that oxidative damage is an important factor for the development of irreversible neuronal damage. On the other hand, our studies have shown that the degree to which lactate accumulates during ischemia is critical for restitution.
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PMID:Reversible ischemia of the brain: biochemical factors influencing restitution. 693 4

Hyper-, normo-, and hypoglycemic rats were exposed to 10 min of complete cerebral ischemia. Regional cerebral blood flow (CBF), blood-brain glucose transfer, and cerebral consumption of oxygen and glucose were measured before, as well as three and 60 minutes after ischemia. Three min after ischemia, no differences were observed between the 3 groups of rats. One h after ischemia, the hyperglycemic rats in comparison to those of the other groups had similar whole-brain CBF and glucose consumption but appreciately lower oxygen consumption, indicating continued non-oxidative use of glucose in the hyperglycemic group. In general, regional CBF values exceeded the control value by 100-200% 3 min after ischemia and were reduced to 50% of control at 1 h after ischemia, at which time the rats were still comatose. In the brain stem of hyperglycemic rats, blood flow, however, remained elevated after ischemia. Thus, the significantly increased mortality observed in rats hyperglycemic before, during and after ischemia (Siemkowicz & Hansen 1978) was the result, not of impaired postischemic CBF, but of ischemic or postischemic damage to brain cells. We suggest that the damaging factor in the hyperglycemic group is increased lactacidosis associated with prolonged anaerobic glycolysis.
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PMID:Post-ischemic coma in rat: effect of different pre-ischemic blood glucose levels on cerebral metabolic recovery after ischemia. 721 9

This study explores the influence of severe lactic acidosis in the ischemic rat brain on postischemic recovery of the tissue energy state and neurophysiological parameters. Severe incomplete brain ischemia (cerebral blood flow below 5% of normal) was induced by bilateral carotid artery clamping combined with hypovolemic hypotension. We varied the production of lactate in the tissue by manipulating the blood glucose concentrations. A 30-min period of incomplete ischemia induced in food-deprived animals caused lactate to accumulate to 15-16 mumol g-1 in cortical tissue. Upon recirculation these animals showed: (1) a considerable recovery of the cortical energy state as evaluated from the tissue concentrations of phosphocreatine, ATP, ADP, and AMP; and (2) return of spontaneous electrocortical activity as well as of somatosensory evoked response (SER). In contrast, administration of glucose to food-deprived animals prior to ischemia caused an increase in tissue lactate concentration to about 35 mumol g-1. These animals did not recover energy balance in the tissue and neurophysiological functions did not return. In other experiments the production of lactate during 30 min of complete compression ischemia was increased from about 12 mumol g-1 (normoglycemic animals) to 20-30 mumol g-1 by preischemic hyperglycemia and, in separate animals, combined hypercapnia. The recovery of the cortical energy state upon recirculation was significantly poorer in hyperglycemic animals. It is concluded that a high degree of tissue lactic acidosis during brain ischemia impairs postischemic recovery and that different degrees of tissue lactic acidosis may explain why severe incomplete ischemia, in certain experimental models, is more deleterious than complete brain ischemia.
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PMID:Brain lactic acidosis and ischemic cell damage: 1. Biochemistry and neurophysiology. 732 45

The influence of severe tissue lactic acidosis during incomplete brain ischemia (30 min) on cortex morphology was studied in fasted rats. Production of lactate in the ischemic tissue was varied by preischemic infusions (i.v.) of either a saline or a glucose solution. The brains were fixed by perfusion with glutaraldehyde at 0, 5, or 90 min of recirculation. In saline-infused animals (tissue lactate about 15 mumol g-1), changes observed at 0 and 5 min of recirculation were strikingly discrete: slight condensation of nuclear chromatin, mild to moderate mitochondrial swelling, and only slight astrocyte edema. These changes had virtually disappeared after 90 min recirculation and, at this time, only discrete ribosomal changes were observed. In contrast, glucose-infused rats (tissue lactate about 35 mumol g-1) showed severe changes: marked clumping of nuclear chromatin and cell sap in all cells was already evident at 0 and 5 min recirculation, while mitochondrial swelling was mild to moderate. Although tissue fixation was inadequate at 90 min, the ultrastructural appearance indicated extensive damage. It is concluded that excessive tissue lactic acidosis during brain ischemia exaggerates structural alterations and leads to irreversible cellular damage. A tentative explanation is offered for the paucity (less than 0.2%) of condensed neurons with grossly swollen mitochondria, previously considered a hallmark of ischemic cell injury.
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PMID:Brain lactic acidosis and ischemic cell damage: 2. Histopathology. 732 46

Glucose was infused intravenously into cats prior to cerebral ischemia. Brain concentrations of glucose, measured in 7 regions, were elevated 2.5-fold compared to those of non-infused animals. Ischemia of 15 or 30 minutes duration caused a greater accumulation of lactic acid in the brain of glucose-infused animals. Post-ischemic restitution of cerebral ATP, phosphocreatine, and lactate during 90 minutes of recirculation was severely impaired in the brain of animals pretreated with glucose compared to untreated animals. Thus, excess lactic acidosis may be a major factor interfering with metabolic restitution following cerebral ischemia.
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PMID:Deleterious effect of glucose pretreatment on recovery from diffuse cerebral ischemia in the cat. II. Regional metabolite levels. 741 63

Ischemia was induced for 10 min with a subsequent 60-min reperfusion and the changes of the malondialdehyde (MDA) concentration in the blood samples from the jugular vein were investigated in normo- and hyperglycemic dogs. Selective brain ischemia was evoked by the increase in cerebrospinal fluid (CSF) pressure. The experiments were carried out in 4 experimental groups. In sham operated animals (Group I) the blood MDA concentration did not change. The venous blood MDA content significantly elevated for 10 min after the start of reperfusion in normoglycemic animals (Group II). To study the effect of acidosis during ischemia and reperfusion on brain lipid peroxidation (LP) processes 1 and 2 g/kg glucose infusion was used in Groups III and IV. As an effect of ischemic lactic acidosis due to hyperglycemia the elevation of MDA concentration in the jugular vein blood was higher and it lasted longer than in the cases of normoglycemia. This finding supports the hypothesis that free radical reactions and LP processes play an important role in the enhanced brain damage caused by tissue acidosis.
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PMID:Alterations in malondialdehyde concentration of jugular vein blood following transient brain ischemia. The effect of lactic acidosis. 771 85


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