Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0242706 (hyperoxia)
5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperoxia beyond 1.8 ATA results in a striking reduction of high-pressure neurological syndrome (HPNS) type I convulsion threshold pressures but is without measurable effect on type II convulsions. The synergism is partially or completely reversed by increasing alveolar or tissue CO2 levels. High total pressures (PI) result in striking reductions in the duration of hyperoxic exposure preceding seizure onset (tc). The interaction of hyperoxia and high pressure gives rise to three zones on the PO2-Pt plane. In zone I, Pt less than 30 ATA, the duration of hyperoxia prior to convulsion onset is given by the equation PO2 -- PO2 lim = K/(tc -- tc lim), where PO2 lim and tc lim both decrease with increasing total pressure. Zone II, Pt = 30-50 ATA and PO2 1.8-2.3 ATA, is characterized by a sharp drop in tc, as Pt is increased beyond 30 ATA, to a value near 15 min that is constant within the PO2 limits given. In zone III, Pt greater than 50 ATA and PO2 greater than 0.2 ATA, tc is of the order of 2 min, and the seizures are essentially HPNS seizures only slightly modified by hyperoxia. The data are interpreted as suggesting that zone I represents hyperoxic seizures facilitated by high pressures, whereas zone II represents HPNS type I seizures facilitated by hyperoxia.
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PMID:Synergism of hyperoxia and high helium pressures in the causation of convulsions. 681 23

In experiments on adult animals (rabbit, cat, dog), it has been found that changes during the initial stages of the effect of high oxygen pressure include: stabilization of the main rhythm of the EEG, inhibition of spindle-like activity and onset (or the increase) of interhemispheral asymmetry of the electrocorticogram, the increase of the amplitude of positive wave of primary response and slow negative wave of the evoked potential of the brain cortex, as well as the increase in the threshold level of inhibition of respiration in response to electrical stimulation of the cranial end of the vagal nerve and the increase in the stability of respiration and cardiac activity. These changes are similar to those which take place in the course of progressive evolution of functions of the central nervous system, respiratory and cardio-vascular systems in onto- and phylogenesis. On the basis of this parallelism, it is concluded that the initial (pre-toxic) effect of hyperoxia results in the increase of the activity of evolutionary younger functional systems of the brain. During the continuous effect of hyperoxia, oxygen intoxication of the organism takes place, which include particularly dissolution phenomena in the activity of the brain. These phenomena are most evident during the development of pre-seizure and seizure periods.
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PMID:[Evolutionary physiological analysis of body reactions to oxygen exposure under increase pressure]. 712 6

Glutathione (GSH) administered intraperitoneally significantly prolongs the time to initial seizure and survival time of rats exposed to hyperbaric hyperoxia (HBO). Acivicin is an antitumor antibiotic that is an inhibitor of gamma-glutamyl transpeptidase (GGT), an enzyme necessary for the breakdown and transport across cell membranes of GSH. To determine whether acivicin treatment alters GSH-induced protection from HBO, rats were dosed with 25 mg/kg of acivicin or vehicle 1 h before O2 exposure at an inspired O2 fraction of 1.0 at 4 ATA. Immediately before exposure, rats received GSH (1 mmol/kg) or vehicle. Time to seizure and time to death were recorded during exposure by direct observation. In separate groups of rats on the same dosing schedule, plasma GSH, renal GGT, and brain GGT were measured 15 min after the GSH injection without HBO exposure and 100 min after the beginning of HBO exposure. Renal GGT was decreased to 2.5% of control and brain GGT to 37% of control in the acivicin-dosed rats. Plasma GSH increased 3-fold in rats given acivicin alone, 52-fold in rats given GSH alone, and 84-fold in rats receiving both acivicin and GSH. Rats dosed with GSH alone had significantly prolonged times to seizure and death compared with all other groups. Rats dosed with GSH after receiving acivicin were not protected from HBO despite the large increase in plasma GSH that occurred in these animals. GSH treatment did not increase tissue GSH in lung, liver, or brain at 160 or 200 min of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elimination of glutathione-induced protection from hyperbaric hyperoxia by acivicin. 791 99

Oxygen therapy is administered to decrease tissue hypoxia and to relieve arterial hypoxemia. High concentrations of oxygen are often used in patients with adult respiratory distress syndrome. Supplying oxygen to animals has been known to produce tissue damage, with toxicity increasing with the increase of oxygen concentrations and exposure pressures. End-organ damage from hyperoxia depends on both the concentration of oxygen administered and the oxygen pressure during exposure. Prolonged exposure to hyperbaric oxygen causes central nervous system and pulmonary toxicity, which results in atelectasis, pulmonary edema, and seizures. Lung damage may occur as a result of normobaric hyperoxia. A severe retinopathy (retrolental fibroplasia) occurs in neonates during oxygen exposures. For all of these reasons, the lowest possible concentration of oxygen that relieves tissue hypoxia is recommended in patients with adult respiratory distress syndrome.
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PMID:Oxygen toxicity. 808 71

CNS oxygen (O2) toxicity is complex, and the etiology of its most severe manifestation, O2 convulsions, is yet to be determined. A role for depletion of the brain GABA pool has been proposed, although recent data have implicated production of reactive O2 species, e.g. H2O2, in this process. We hypothesized that the production of H2O2 and NH3 produced by monoamine oxidase (MAO) would lead to depletion of GABA and production of nitric oxide (NO.) respectively, and thereby enhance CNS O2 toxicity. In this study, rats treated with an MAO inhibitor (pargyline) or a nitric oxide synthase inhibitor (LNNA) were protected against O2-induced convulsions. Selected cerebral amino acids including arginine were measured in control and O2 treated rats (6 ATA, 20 min) with or without drug pretreatment. After O2 exposure, the cerebral pools of glutamate, aspartate, and GABA decreased significantly while glutamine content increased relative to control (P < 0.05). After treatment with either enzyme inhibitor, glutamine, glutamate and aspartate concentrations were maintained near control levels. Remarkably, GABA depletion by O2 was not prevented despite protection from seizures by both pargyline and LNNA. The NO. precursor, arginine, was increased significantly in the brain by toxic O2 exposure, but both pargyline and LNNA inhibited this effect. Simultaneous norepinephrine measurements indicated that its storage substantially decreased during hyperoxia (P < 0.05), but this effect too was blocked by either pargyline or LNNA. These data indicate that protection against O2 by these inhibitors is not related to preservation of the GABA pool. More importantly, O2 dependent norepinephrine metabolism and NO. synthesis appear to be interactive during CNS O2 toxicity.
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PMID:Cerebral amino acid, norepinephrine and nitric oxide metabolism in CNS oxygen toxicity. 846 4

We tested the effect of caffeine, on hyperoxia-induced seizures. Thirty-seven rats with chronic cortical electrodes were injected i.p. with caffeine (1.25, 2.5, and 10 mg/kg) or vehicle before exposure to 0.5 MPa oxygen and 17 rats to oxygen with 5% CO2 at 0.5 MPa. EEG monitoring and spectral analysis of EEG activity were carried out. Caffeine significantly prolonged the latent period to the onset of seizures (P < 0.05 in ANOVA), in a dose-related manner. Our results suggest that caffeine may be used in low doses for protection against hyperoxia-induced seizures.
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PMID:Caffeine attenuates CNS oxygen toxicity in rats. 857 77

Fever induces seizures in infants with febrile convulsions or epilepsy. Hyperpnea induced by fever may contribute to the induction of these seizures. In order to examine this possibility, we evaluated the effect of changes in arterial blood gas tension on hyperthermia-induced seizures in developing rats. Electrical seizure discharges were induced by application of infra-red rays on the skull of rats under mechanical ventilation with different respiratory conditions. There was positive correlation between pCO(2) and the seizure threshold (ST) defined as a latency from the start of hyperthermia to the occurrence of seizures: ST (seconds, s) = 2.36 pCO(2) + 0.05 (R(2) = 0.80, P < 0.001). Seizure duration (SD) was longer at lower pCO(2) level: 18 (6-33) (median, range) s at pCO(2) ranging from 23 to 26 mmHg vs. 0 (0-7) s at pCO(2) ranging from 35 to 57 mmHg (P < 0.01). Hypoxia significantly increased ST: 84 (61-100) s at P0(2) ranging from 53 to 76 mmHg vs. 60 (51-72) s at P0(2) ranging from 87 to 131 mmHg (P < 0.01). Hyperoxia prolonged SD: 27 (10-30) s at P02 ranging from 100 to 170 mmHg vs. 9 (0-23) at P0(2) ranging from 53 to 93 mmHg (P < 0.02). Hypocarbia caused by fever-induced hyperpnea probably contributes to the generation of fever-induced seizures.
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PMID:The influence of blood gas changes on hyperthermia-induced seizures in developing rats. 886 25

We tested the effect of moderate food or water deprivation and a combination of the two on sensitivity to hyperoxia-induced seizures in rats. Seventy rats with chronic cortical electrodes were exposed to seven experimental protocols: starvation, dehydration or a combination of both for 24 or 36 h, prior to exposure to 0.5 Mp(a)O2. Blood glucose and hematocrit were measured before and after exposure to hyperbaric oxygen (HBO). Starvation and dehydration significantly prolonged the latent period to the onset of hyperoxia-induced seizures (P < 0.05 in the Tukey test), in a dose-related manner. Our results suggest that deprivation of food or water, prior to exposure to HBO, may postpone the development of hyperoxia-induced seizures.
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PMID:Starvation and dehydration attenuate CNS oxygen toxicity in rats. 924 77

The involvement of the L-arginine-nitric oxide (NO) pathway in the pathogenesis of hyperoxia-induced seizures was studied by using agents controlling NO levels. We selected two inhibitors of nitric oxide synthase, the systemic inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) and the novel cerebral-specific inhibitor 7-nitroindazole, and two generators of NO, the NO donor S-nitroso-N-acetylpenicillamine and the physiological precursor L-arginine. Rats with chronic cortical electrodes were injected intraperitoneally with different doses of one of the agents or their vehicles before exposure to 0.5 MPa O2 and O2 with 5% CO2 at an absolute pressure of 0.5 MPa. The duration of the latent period until the onset of electrical discharges in the electroencephalogram was used as an index of central nervous system O2 toxicity. The two nitric oxide synthase inhibitors L-NAME and 7-nitroindazole significantly prolonged the latent period to the onset of seizures on exposure to both hyperbaric O2 and to the hypercapnic-hyperoxic mixture. Pretreatment with the NO donor S-nitroso-N-acetylpenicillamine significantly shortened the latent period, whereas L-arginine, the physiological precursor of NO, significantly prolonged the latent period to onset of seizures. Our results suggest that the L-arginine-NO pathway is involved in the pathophysiology of hyperoxia-induced seizures via various regulating mechanisms.
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PMID:L-arginine-NO pathway and CNS oxygen toxicity. 957 10

It seems clear that the abundance of potential treatment options reflects the dearth of proved, effective options. Thus, although we appear to be on the brink of many potentially major breakthroughs in treatment, there currently remains a multitude of unanswered questions and the need for further study. At this point clinical recommendations must be limited to supportive care with moderation: oxygenation without hyperoxia; ventilation without hypocarbia; avoiding extremes of blood pressure, hematocrit, blood glucose, and body temperature. Unfortunately, data from human trials are extremely limited and often poorly controlled. Furthermore, even those few existing human studies have rarely--if ever--dealt with newborns infants (Table 2). In addition, many of the existing studies do not relate to generalized asphyxia but rather to single-organ reperfusion insults. Finally, there is the critical issue of timing. Unfortunately, much of the existing experimental data relate to prophylaxis rather than treatment, severely limiting their potential for clinical applicability. Interventions may have quite different effects when administered at different phases of this most intricate process. Hyperglycemia, for example, may be neuroprotective before an insult but detrimental if induced after an asphyxial episode. Conversely, the NMDA blocker MK-801 can adversely affect outcome when given before a global asphyxial insult but can reduce seizure-related damage when given during the hyperexcitability phase. Insulin-like growth factor is also neuroprotective only when given after an insult, but it is not helpful if given before. An intimate understanding of the pathophysiologic processes involved is essential before any attempts at applying the diverse data derived from numerous animal studies to the human situation in an intelligent manner. Future studies may focus on cocktails of different mixtures of the compounds discussed or on single multipotential drugs, which would make possible a multipronged approach. However, it is essential to investigate fully the potential for toxic drug interactions, as some combinations may be produce serious consequences. For example, Gluckman and Williams evaluated the potential of combining calcium channel blockers with NMDA receptor antagonists in hypoxic-ischemic rats and found that this combination led to rapid cardiovascular collapse. Other enticing approaches for future investigations will probably include some genetic-engineering-related studies in attempt to enhance endogenous antioxidant defenses with regulon stimulation or the administration of neurotrophic growth factors. Unavoidably, the trip from the laboratory to the bedside must of necessity be an arduous and rigorous one.
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PMID:Ischemia and reperfusion injury. The ultimate pathophysiologic paradox. 977 46


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