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)

Previous work has shown that irrespective of the route of exposure methyl isocyanate (MIC) caused acute lactic acidosis in rats (Jeevaratnam et al., Arch. Environ. Contam. Toxicol. 19, 314-319, 1990) and the hypoxia was of stagnant type due to tissue hypoperfusion resulting from hypovolemic hypotension in rabbits administered MIC subcutaneously (Jeevarathinam et al., Toxicology 51, 223-240, 1988). The present study was designed to investigate whether MIC could induce histotoxic hyperoxia through its effects on mitochondrial respiration. Male Wistar rats were used for liver mitochondrial and submitochondrial particle (SMP) preparation. Addition of MIC to tightly coupled mitochondria in vitro resulted in stimulation of state 4 respiration, abolition of respiratory control, decrease in ADP/O ratio, and inhibition of state 3 oxidation. The oxidation of NAD(+)-linked substrates (glutamate + malate) was more sensitive (five- to sixfold) to the inhibitory action of MIC than succinate while cytochrome oxidase remained unaffected. MIC induced twofold delay in the onset of anerobiosis, and cytochrome b reduction in SMP with NADH in vitro confirms inhibition of electron transport at complex I region. MIC also stimulated the ATPase activity in tightly coupled mitochondria while lipid peroxidation remained unaffected. As its hydrolysis products, methylamine and N,N'-dimethylurea failed to elicit any change in vitro; these effects reveal that MIC per se acts as an inhibitor of electron transport and a weak uncoupler. Administration of MIC sc at lethal dose caused a similar change only with NAD(+)-linked substrates, reflecting impairment of mitochondrial respiration at complex I region and thereby induction of histotoxic hypoxia in vivo.
Toxicol Appl Pharmacol 1992 Dec
PMID:In vitro and in vivo effect of methyl isocyanate on rat liver mitochondrial respiration. 147 Nov 48

This study was designed to determine how several factors interact to modify the cerebral ischemic pressor response (CIR) in anesthetized rabbits. After the carotid sinus and aortic nerves were bilaterally sectioned, blood flow through the left internal carotid artery (ICF), which was surgically restricted as the sole route of blood supply to the brain, was reduced by a servo-controller during ventilation with room air, and 8% and 90% O2 and 2 and 5% CO2 gas mixtures. Blood flow (MBF), tissue PO2, PCO2, and interstitial pH were measured in the rostral ventrolateral medulla. Internal carotid arterial pressure, tissue PO2, and MBF decreased proportionately as ICF decreased in the range from 4 to 0 ml/min. Hypoxia significantly increased the rise in renal nerve activity (RNA) and CIR caused by cerebral ischemia, while hyperoxia significantly decreased them. Hypercapnia had almost no influence on the increases in RNA and mean arterial pressure produced by cerebral ischemia. CIR showed a much higher correlation with changes in tissue PO2 than with the other factors. We examined how these factors interact to modify CIR and found that central hypoxia is the main factor in producing CIR.
Am J Physiol 1992 Dec
PMID:Effects of hypoxia, hyperoxia and hypercapnia on graded cerebral ischemic responses in rabbits. 148 7

Death in normobaric hyperoxia was related in the past to pulmonary insufficiency of the edematous lung. However, high arterial O2 tension on final collapse led to the suggestion that the heart and not the lung is the first organ that fails. We measured aortic flow, coronary flow, left ventricular pressure, affluent and effluent PO2, PCO2, and pH in the working heart excised from control and normobaric O2-exposed rats (51-63 h). The oxygen consumption (VO2) of experimental hearts was not different from control, but mechanical power output (PVAP) (calculated from pressure-volume area) was reduced as a function of O2 exposure time. Myocardial contractility indexes, maximal elastance and maximal time derivative of pressure, increased as a function of O2 exposure time, being below control values after 50 h and above control values after 60 h. The individual slopes for the regression of VO2 vs. PVAP rose as a function of exposure time from values below control after 50 h exposure to values above control after 60 h. Energetic efficiency (PVAP/VO2) decreased as a function of O2 exposure time and points to possible heart failure in the intact animal. After 50 h O2 exposure the heart was energetically more efficient than the control. Possible changes in the heart are discussed.
J Appl Physiol (1985) 1992 Dec
PMID:Heart energetic efficiency in O2-exposed rats studied in isolated working heart. 149 Sep 35

The changes of free radicals and the effect of anisodamine and vitamin E on hyperoxic lung injury were studied. Ninety adult Wistar rats were exposed to greater than 95% O2. Nine a normal rats served as controls. The animals in group A were only exposed to hyperoxia, while in group B and C, they were treated intramuscularly with anisodamine (15 mg/kg, bid) and vitamin E (75 mg/kg, bid) respectively. The rats in each group were killed after 12, 24 or 48 hours oxygen exposure. The blood and lung were examined for SOD, GSH-PX and MDA. In Group A, the quantity of peroxide free radical increased 20%. The activity of SOD and GSH-PX decreased and MDA increase were in lower degree. Changes of SOD, GSH-PX, MDA, PaO2 and lung damage were also in lower degree. The results indicated that the increase of oxygen free radicals may be the pathophysiological factor in hyperoxic lung injury.
Zhonghua Jie He He Hu Xi Za Zhi 1991 Dec
PMID:[The mechanism of the effects of 654-2 and vitamin E on hyperoxic lung injury]. 166 87

In anaesthetized rats, ventilatory stimulation induced by phentolamine, an alpha sympatholytic agent, emphasizes the role of some adrenergic mechanisms in the control of the respiratory centres activity. Phentolamine (5 and 10 mg.kg-1, iv) stimulates ventilation after a 4 s latency, tidal volume and respiratory rate being both increased. A same response can also be provoked 10 min later, by a second identical iv administration, systemic blood pressure remaining then stable at its previous low level. Hyperventilation is also observed when phentolamine is injected in totally denervated rats, without any remaining baro- or chemosensitivity. Stimulation is thus due to a central activity in relation with the release of inhibitory influences. Phentolamine also causes hyperventilation after prazosin pretreatment indicating that the alpha 1 adrenergic blockade is not involved in the post-phentolamine stimulation. This is an alpha 2 adrenergic transmission dependent mechanism. Variation of the systemic blood pressure is not the main mechanism involved in the hyperventilation induced by phentolamine. Meanwhile, baroreceptor activity modulates the central response to the drug, as shown by the negative influence of the post-vasopressin arterial hypertension. Hyperoxia is also a modulating factor acting by two ways: an inhibition of the peripheral chemoreceptors activity is added to an arterial hypertension. On the other side, activation of these chemoreceptors by almitrine bismesilate increases the respiratory responses to phentolamine. As already shown by one of us (Lagneuax, 1986), phentolamine pretreated rats are more responsive to hypoxia and to almitrine. Moreover, these phentolamine pretreated rats are protected against cardiovascular collapses and against apnea, frequently observed during hypoxia without CO2 compensation.
Arch Int Physiol Biochim 1990 Dec
PMID:[Alpha 2 adrenergic control of ventilation in the rat]. 170 84

Steady-state levels of mRNAs for the three surfactant-associated proteins, SP-A, SP-B, and SP-C, were measured in a primate model of premature birth and survival. These values were determined by Northern and quantitative slot blot analyses of total lung RNA during both in utero and extrauterine development of the fetus as well as in response to hyperoxic exposure. The composition and surface properties of surfactant were also analyzed to determine the effect of differential expression of the surfactant proteins on the overall composition and function of surfactant. The data clearly demonstrate that the regulation of surfactant mRNA levels in the premature fetus is under complex physiological control. Interruption of in utero development by premature birth results in increased levels of all three surfactant mRNAs, presumably in response to precocious initiation of air breathing. Within the first 24 h after parturition both SP-B and SP-C mRNA levels are increased beyond the levels found in the full-term fetal controls. Expression of mRNA for these genes peaks on day 2 and thereafter drops to levels below that found on day 1. However, response of the SP-A gene to premature birth is slow and transcripts from this gene lag considerably behind values found in the full-term fetus. Furthermore, exposure of the premature fetus to hyperoxia results in an increase in the steady-state levels of SP-B and SP-C mRNA without significant changes in SP-A. Defects in the ability of the SP-A gene to respond to extrauterine exposure and hyperoxia may be contributing to development of bronchopulmonary dysplasia, a common clinical complication of premature birth in humans.
Am J Physiol 1991 Dec
PMID:Alterations in surfactant protein gene expression associated with premature birth and exposure to hyperoxia. 176 59

In awake lambs we investigated the role of the peripheral chemoreceptors in producing dynamic ventilatory (VE) responses to CO2. The immediate VE response, within 15 s, to transient CO2 inhalation was studied in two groups: 1) five lambs before carotid denervation and 2) the same lambs after carotid denervation. The time course of VE responses during the first 60 s after a step change to 8% inspired CO2 was also studied in lambs after carotid denervation and in a group of six carotid body-intact lambs 10-11 days of age. Acute CO2 responses were assessed using step changes to various concentrations of CO2 + air and CO2 + O2, while VE was recorded breath by breath. Intact lambs exhibited a brisk VE response to step changes in CO2, beginning after 3-5 s. Hyperoxia altered but did not suppress the dynamic VE CO2 response when the carotid chemoreceptors were intact. Carotid denervation markedly reduced the VE response during the first 25 s after a CO2 step change, revealing the time delay required for the central chemoreceptors to produce an effective VE response. The residual VE response remaining after CD was thought to be mediated by the remaining aortic body chemoreceptors and was eliminated by adding O2 to the CO2 challenges. However, after carotid denervation, even with CO2 + hyperoxia, the onset of a small tidal volume response was apparent by 10-12 s.(ABSTRACT TRUNCATED AT 250 WORDS)
J Appl Physiol (1985) 1991 Dec
PMID:Dynamic ventilatory responses to CO2 in the awake lamb: role of the carotid chemoreceptors. 177 13

The effects of inspired O2 on diaphragm tension development during fatigue were assessed using isovelocity (n = 6) and isometric (n = 6) muscle contractions performed during a series of exposures to moderate hypoxia [fraction of inspired O2 (FIO2) = 0.13], hyperoxia (FIO2 = 1), and severe hypoxia (FIO2 = 0.09). Muscle strips were created in situ from the canine diaphragm, attached to a linear ergometer, and electrically stimulated (30 Hz) to contract (contraction = 1.5 s/relaxation = 2 s) from optimal muscle length (Lo = 8.9 cm). Isovelocity contractions shortened to 0.70 Lo, resulting in a mean power output of 210 mW/cm2. Fatigue trials of 35 min duration were performed while inspired O2 was sequentially changed between the experimental mixtures and normoxia (FIO2 = 0.21) for 5-min periods. In this series, severe hypoxia consistently decreased isovelocity tension development by an average of 0.1 kg/cm2 (P less than 0.05), which was followed by a recovery of tension (P less than 0.05) on return to normoxia. These responses were not consistently observed in isometric trials. Neither isovelocity nor isometric tension development was influenced by moderate hypoxia or hyperoxia. These results demonstrate that the in situ diaphragm is relatively insensitive to rapid changes in O2 supply over a broad range and that the tension development of the shortening diaphragm appears to be more susceptible to severe hypoxia during fatigue. This may reflect a difference in either the metabolic or blood flow characteristics of shortening contractions of the diaphragm.
J Appl Physiol (1985) 1991 Dec
PMID:Muscle shortening increases sensitivity of fatigue to severe hypoxia in canine diaphragm. 177 28

Cardiopulmonary responses to prolonged hyperoxia and their relationships to the development of lung pathology have not been fully characterized in primates. In this study, circulatory hemodynamics and pulmonary function, vascular permeability, and leukocyte sequestration were measured in male baboons after 100% O2 exposure and related to ultrastructural changes of lung injury by electron microscopy. Three groups of animals were exposed to 100% O2 in an exposure cage for 40, 66, and 80 h, respectively. A fourth group of animals was exposed in a cage for 80 h and then anesthetized and ventilated with 100% O2 for additional time. These animals were exposed for a total duration of 110 h or until death from the injury. Physiological responses to hyperoxia were characterized by decreases in total lung capacity and inspiratory capacity at 80 and 110 h. A significant increase in pulmonary leukocyte accumulation was noted by 80 h. Extravascular lung water and permeability surface-area product increased at 80 and 110 h. Cardiac output and stroke volume also decreased, and systemic vascular resistance increased after 80 and 110 h of hyperoxia. Histopathological changes were present in the lungs of all but the 40-h exposure group. Animals exposed for 66 h showed endothelial injury and neutrophil accumulation. By 80 h, animals showed endothelial cell destruction, interstitial edema, and type I cell injury. At 110 h, animals showed substantial destruction of endothelial and type I epithelial cells, exposure of alveolar basement membrane, congestion of capillaries, and substantial interstitial edema. The data indicate that histological changes by electron microscopy precede physiological responses to hyperoxic pulmonary injury in baboons by as much as 14 h and that the physiological responses to early hyperoxic injury are relatively insensitive to the pathological injury.
J Appl Physiol (1985) 1991 Dec
PMID:Responses of baboons to prolonged hyperoxia: physiology and qualitative pathology. 177 33

Whereas glucocorticoid administration to pregnant rats produces parallel acceleration of lung surfactant and antioxidant enzyme system maturation in late gestation, prenatal thyroid hormone treatment results in acceleration of surfactant maturation, with a paradoxical decrease in antioxidant enzyme (AOE) development. In these studies, we tested whether prenatal thyroid releasing hormone (TRH) treatment would act like prenatal thyroid hormone on pulmonary surfactant and AOE system maturation and whether combined prenatal treatment with TRH plus dexamethasone (DEX) would alter these effects. Secondly, we tested whether prenatal TRH and prenatal TRH plus DEX would inhibit the ability of newborn rats to respond to hyperoxia with protective increases in AOE activities. Results of the developmental studies revealed significantly increased fetal lung disaturated phosphatidylcholine content with significantly decreased pulmonary AOE activities as a result of prenatal TRH treatment that was not reversed with the addition of DEX. Combined TRH plus DEX treatment resulted in statistically significant decreases in body weight, lung weight, and lung weight to body weight ratios at both 21 and 22 d of gestation; growth effects were not seen with TRH alone. In terms of hyperoxic AOE response, despite being born with lower baseline AOE levels, the newborn animals prenatally treated with TRH or TRH plus DEX were able to induce a normal pulmonary AOE response to high O2 exposure. Although requiring further investigation, this reassuring finding suggests that clinical prenatal therapy with TRH or the combination of TRH plus DEX is not contraindicated for those infants delivered prematurely who go on to require intensive hyperoxic therapy.
Pediatr Res 1991 Dec
PMID:Prenatal hormone treatment with thyrotropin releasing hormone and with thyrotropin releasing hormone plus dexamethasone delays antioxidant enzyme maturation but does not inhibit a protective antioxidant enzyme response to hyperoxia in newborn rat lung. 180 47


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