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

We did two studies to see if severe neutropenia might reduce the severity or delay development of O2-induced lung microvascular injury. First, we treated 11 rabbits with nitrogen mustard until their circulating neurophil count decreased to less than 50/microliters of blood, after which the rabbits breathed pure O2 until death; nine other rabbits received no nitrogen mustard and had normal numbers of circulating neutrophils during O2 breathing. All rabbits died of respiratory failure with pulmonary edema, and although chemotherapy decreased the number of neutrophils in the lungs by greater than 90%, it did not influence survival time or extravascular lung water content. To see if severe neutropenia might slow the development of O2-induced lung microvascular injury, we assessed the effects of sustained hyperoxia on lung fluid balance in unanesthetized lambs treated with hydroxyurea, so that their absolute neutrophil count was less than 50/microliters of blood. We measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and concentrations of protein in lymph and plasma during a 2- to 4-h control period and then daily for 2 to 4 h as the lambs continuously breathed pure O2. After 3 days of hyperoxia, lymph flow doubled and the concentration of protein in lymph increased from 3.3 +/- 0.5 to 4.2 +/- 0.3 g/dl. Tracer studies with 125I-albumin before and 3 days after the start of O2 breathing confirmed the development of increased lung vascular permeability to protein. All lambs died of respiratory failure with pulmonary edema after 3-5 days in O2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen-induced lung microvascular injury in neutropenic rabbits and lambs. 398 Mar 93

The response of the injured lung to hyperoxia is uncertain. In the present study, we evaluated the effects of 100% oxygen exposure for 120-168 h in mechanically ventilated baboons with or without previous diffuse alveolar damage (DAD) induced by oleic acid. These two groups were compared with another group of six baboons previously studied in our laboratory in which DAD induced with oleic acid was followed by ventilation with 40% oxygen. Oleic acid infusion caused a prompt reduction in total lung capacity, static compliance, and diffusion capacity and an increase in lung tissue volume. The magnitude and course of oleic acid lung injury was similar for 4 days in animals breathing 100% or 40% O2. Animals breathing 100% O2 without previous lung injury developed significant decreases in total lung capacity, oxygenation, and diffusion capacity after 72 h of hyperoxia. By 120 h, lung function was similarly impaired in both 100% O2-breathing groups, and rapidly worsening pulmonary edema appeared radiographically between 5.5 and 7 days in all O2-exposed animals. Subsequent weaning was successful in only three animals after 100% O2 exposure. All but one animal in the 40% O2 group were easily weaned. Histologic changes between 6 and 14 days in 100% O2 animals showed a marked proliferative response, particularly of type 2 cells; no differences were found due to prior oleic acid injury. Resolution of this process occurred in a surviving animal, resulting in focal fibrotic residua at 6 weeks, similar to that observed in 40% O2 oleic acid-treated survivors. Previous lung injury due to oleic acid did not modify the response of the baboon lung to hyperoxia.
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PMID:Hyperoxia exposure in mechanically ventilated primates with and without previous lung injury. 407 53

Toxic, partially reduced metabolites of oxygen (toxic oxygen radicals) are increasingly implicated in acute leukocyte-mediated tissue injury. To further probe the roles of oxygen radicals in acute lung edema, I studied the effects of a recently described and very potent oxygen radical scavenger, dimethylthiourea (DMTU) (Fox, R. B., R. N. Harada, R. M. Tate, and J. E. Repine, 1983, J. Appl. Physiol., 55:1456-1459) on polymorphonuclear leukocyte (PMN) oxidant function and on two types of lung injury mediated by oxygen radicals and PMN. DMTU (10 mM) blocked 79% of hydroxyl radical (OH) production by PMN in vitro without interfering with other PMN functions, such as O-2 production, myeloperoxidase activity, chemotaxis, degranulation, or aggregation. When isolated rat lung preparations were perfused with PMN activated to produce OH, lung weights were increased from 2.3 +/- 0.2 to 11.2 +/- 0.8 g. DMTU (10 mM) prevented 70% of these increases (lung weights, 5.0 +/- 1.1 g, P less than 0.005). Finally, when intact rats were exposed to 100% O2 for 66 h, lung weight:body weight ratios were increased from 5.78 +/- 0.33 to 8.87 +/- 0.16 g. DMTU (500 mg/kg) prevented 83% of this hyperoxia-induced lung edema in vivo (lung:body weight ratios, 6.05 +/- 0.21, P less than 0.001). Pharmacokinetic studies showed that DMTU diffused effectively into lung interstitial fluids and had a relatively long half-life (25-35 h) in the circulation. Because a variety of oxygen radicals, such as superoxide (O-2), hydrogen peroxide (H2O2), or OH are produced by PMN, there is usually some uncertainty about which one is responsible for injury. However, in these studies, DMTU did not scavenge O-2 and scavenged H2O2 only very slowly while scavenging OH very effectively. Therefore, DMTU may be useful in the investigation of the roles of oxygen radicals, especially OH, in acute granulocyte-mediated tissue injury.
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PMID:Prevention of granulocyte-mediated oxidant lung injury in rats by a hydroxyl radical scavenger, dimethylthiourea. 609 May 4

Elevated levels of angiotensin-converting enzyme activity (ACE) in bronchoalveolar lavage fluid (BAL) have been used as a specific marker for pulmonary endothelial cell injury associated with high permeability lung edema. Alternatively, however, BAL-ACE elevations might reflect a nonspecific leak of plasma proteins into bronchoalveolar spaces. To investigate the cause of BAL-ACE elevations in high permeability lung injury states, we measured ACE and protein concentrations in BAL from isolated perfused rabbit lungs injured with oleic acid or hyperoxia. Although BAL-ACE was elevated, we found no increase in the BAL-ACE:protein ratio over values from control preparations, despite the presence of marked nonhydrostatic lung edema. We conclude that, in the experimental setting of nonhydrostatic lung edema, BAL-ACE elevations are no more helpful in identifying acute lung injury than are elevated BAL-protein levels.
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PMID:Nonspecificity of elevated angiotensin-converting enzyme activity in bronchoalveolar lavage fluid from high permeability lung edema states. 632 28

Various indirect methods have implicated the polymorphonuclear leukocyte (PMN) as being an important, but not an absolutely necessary, factor in hyperoxia-associated pulmonary edema. By utilizing the cell free isolated perfused rabbit lung model, we demonstrated that the addition of purified, unstimulated granulocytes into the pulmonary artery of hyperoxia exposed lungs resulted in a synergistic edematogenic effect which was statistically significant (p less than 0.05) within only four hours. In addition, significant nonhydrostatic pulmonary edema was produced by both hyperoxia (p less than 0.02) and the addition of PMNs (p = 0.001) when these variables were independently analyzed. These findings help to establish a direct interaction between the role of the PMN and hyperoxia in high permeability lung edema.
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PMID:Granulocytes and hyperoxia act synergistically in causing acute lung injury. 652 83

The antioxidant enzyme superoxide dismutase (SOD) found in the cytosol of eucaryotic cells and the plasma protein ceruloplasmin are copper containing proteins though to be important in providing protection from oxygen toxicity. To investigate the hypothesis that copper deficiency in the rat could result in decreased lung SOD activity and plasma ceruloplasmin concentration resulting in increased susceptibility to O2 lung damage, we performed a series of experiments exposing copper-deficient and control rats to normobaric and hyperbaric hyperoxia. Lung SOD activity in the copper-deficient rats was found to be 56% of control and ceruloplasmin content was 6% of control. The copper-deficient rats exhibited increased mortality and enhanced pulmonary toxicity as evidenced by increased pathologic damage and lung edema during the normobaric exposure to 85% O2. Copper-deficient animals also showed increased susceptibility to a hyperbaric exposure of 4 ata of 100% O2 with a decreased time of survival. The copper-deficient rat represents a new model for the study of oxidant injury.
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PMID:Enhanced pulmonary toxicity in copper-deficient rats exposed to hyperoxia. 672 91

Knowledge of the interrelation of the central nervous system-respiratory axis is crucial to the management of patients with head injuries with or without concomitant pulmonary-thoracic problems. Damage to the central nervous system (CNS) can result in unexplained hypoxemia, noncardiac pulmonary edema, altered patterns of respiration, and an increased risk of aspiration. The damaged thorax and lung can contribute to brain ischemia and rises in intracranial pressure. The treatment of one end of the CNS-respiratory axis is not without effect on the other end of the continuum. Corticosteroids, diuretics, mannitol, iatrogenic hyperventilation, barbiturates, and vasopressors are used in the management of patients with head trauma, but may have an impact on oxygenation and ventilation. When positive end expiratory pressure is used in the management of a pulmonary process, it should be optimized and used with caution while monitoring for its effect on intracranial pressure. Pulmonary toilet, while remaining a necessity, must be performed in a manner so as to minimize potential negative effects on the brain. Hyperoxia and hypothermia should be avoided. Mechanical ventilation should be used as dictated by the desired PaCO2 and not as a mandatory adjunct to endotracheal intubation.
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PMID:Pulmonary effects of head trauma. 679 86

Since the effect of prolonged exposure to high concentrations of oxygen on regional ventilation and perfusion has not been previously, a reproducible primate model of oxygen toxicity was developed to investigate the pathophysiologic changes that occur. Regional ventilation and perfusion were measured by 133Xe techniques in 10 baboons before and after 108 hours of continuous exposure to an inspired oxygen concentration of more than 90%. Arterial blood gases, shunt fraction (QS/QT), cardiac output, physiologic dead space (VD/VT), and pulmonary vascular resistance were also measured. Light and electron microscopic histology confirmed early pathologic changes of oxygen toxicity in every animal after exposure. PaO2 in room air decreased markedly after exposure from 90 +/- 4 to 46 +/- 5 mm Hg, and QS/QT rose to 30 +/- 2%. VD/VT, PaCO2, and pH were not altered by exposure to hyperoxia. Similarly, cardiac output and pulmonary vascular resistance remained unchanged. The distribution of regional ventilation and perfusion remained normal during and after prolonged high-oxygen exposure. Early oxygen toxicity was characterized by profound hypoxemia without regional ventilation-perfusion mismatch. Although impaired diffusion through a thickened alveolar membrane may be partially responsible for this hypoxemia, the markedly increased alveolar-arterial oxygen gradient when FIO2 = 1.0 indicates that shunting at the alveolar level (secondary to absorptive collapse or pulmonary edema) is a major cause of the hypoxemia.
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PMID:Effects of oxygen toxicity on regional ventilation and perfusion in the primate lung. 722 86

To determine the effects of high oxygen (O2) tension on pulmonary vascular reactivity, we exposed rats either to 100% O2 for 48 hours or 40% O2 for 3 to 5 weeks. Lungs from all rats were isolated, blood perfused and ventilated, and pressor responses to airway hypoxia and to infused angiotensin II were measured. We found that chronic subtoxic hyperoxia did not augment subsequent hypoxic vasoconstriction, and that 48 hrs of 100% O2 markedly blunted hypoxic vasoconstriction. Meclofenamate restored hypoxic vasoconstriction to control levels in the lungs with blunted responses. Evidence for O2 toxicity in the lungs exposed to 100% O2 included interstitial swelling with alveolar exudates seen by light microscopy, and lung edema by water content calculations. We conclude that 1) chronic subtoxic hyperoxia does not influence subsequent hypoxic vasoconstriction, and 2) a dilator prostaglandin produced in the lung is a potent inhibitor of hypoxic vasoconstriction in O2 toxic lungs.
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PMID:Blunted pulmonary pressor responses to hypoxia in blood perfused, ventilated lungs isolated from oxygen toxic rats: possible role of prostaglandins. 729 93

The etiology of shocklung is diverse. All causes lead to a lesion of the alveolar-capillary membrane with interstitial and subsequent alveolar edema. The clinical manifestations, although variable, are progressive and can be divided into 3 stages, which are the expression of a decrease in pulmonary compliance and of hypoxemia due to a ventilation-perfusion defect (shunt effect). The diagnosis of shocklung must be differentiated from pulmonary edema of cardiac origin by right heart catheterization and demonstrate a normal capillary pressure, a pulmonary hypertension with increased pulmonary resistance and a normal or increased cardiac output. A decreased PaO2 is the first sign of a ventilation-perfusion imbalance. The problem of alveolar-capillary O2 transfer is better defined by the alveolar-arterial O2 difference, the calculation of quantity of the intrapulmonary shunt and the hyperoxia curve. The daily analysis of the hyperoxia curve allows for a better appreciation of the clinical status than the clinical and radiological signs. The prognosis of the shockening is poor inspite of better reanimation technics. The mortality is about 50% and depends on 3 factors: etiology, early diagnosis and correction of the primary insult.
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PMID:[The adult respiratory distress syndrome. Clinical signs, radiology and biological data (author's transl)]. 736 93


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