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

We carried out morphometric studies to assess the effects of increasing durations of hyperoxic exposure on the developing rat lung and to evaluate the potential for new growth and for regression of structural abnormalities on return to room air. From day 10 of life Sprague-Dawley rats were either exposed to hyperoxia (0.8FIO2) for 2-8 wk or were removed after 2 wk and allowed to "recover" in room air for 2-6 wk. Litter mates maintained in room air served as age matched controls. Every 2 wk experimental and control rats from each group were weighed and killed. The heart and lungs were removed, the pulmonary artery was injected with barium-gelatin, and the lung was fixed in formalin in the inflated state. Morphometric assessments were made of right and left ventricular weights, lung volume, axial artery lumen diameter, alveolar number and concentration, and arterial number, concentration and muscularity. Rats continuously exposed to hyperoxia and rats exposed for only 2 wk showed the same degree of impaired parenchymal lung growth, as judged by a decrease in the concentration and number of alveoli. A significant decrease in arterial concentration, increase in muscularization of peripheral arteries, and medial hypertrophy of muscular arteries occurred after 2 wk of hyperoxia. Despite an initial trend toward regression, these features became progressively severe with continued hyperoxic exposure and by 8 wk were associated with a decreased arterial lumen diameter, with right ventricular hypertrophy and with failure to thrive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperoxia-induced pulmonary vascular and lung abnormalities in young rats and potential for recovery. 293 74

This study describes the pulmonary vascular lesions in rat pulmonary arteries and altered right ventricular weight after 1) prolonged exposure to hyperoxia (87% O2 for 4 weeks) at ambient pressure, 2) weaning from hyperoxia to air over 7 days, and 3) return to breathing air for 2, 4, or 8 weeks. Hyperoxia for 28 days narrows the lumen of intraacinar and preacinar arteries, increasing the percent medial thickness (%MT) by reducing the external diameter and thickening medial muscle. The ratio of patent intraacinar arteries to alveoli is significantly reduced, and pulmonary vascular obstruction and obliteration is evident by electron microscopy. A higher proportion of intraacinar and preacinar arteries have muscle in their wall than in the normal lung: in alveolar wall and duct regions, the proportion of partially muscular and muscular intraacinar arteries increases at the expense of nonmuscular ones (for both regions P chi 2 less than or equal to 0.001); and in arteries associated with terminal bronchioli and bronchioli the proportion of muscular arteries increases at the expense of partially muscular ones (for both regions P chi 2 less than or equal to 0.001). Both after weaning and after return to breathing air lumen size increases; but, even after 8 weeks, the %MT remains significantly increased, and the ratio of intraacinar arteries to alveoli is less than normal. After weaning, the proportion of muscularized intraacinar and preacinar arteries is similar to that after hyperoxia. Two weeks after return to breathing air, the proportion of muscularized alveolar wall and duct arteries is greater (for both regions P chi 2 less than or equal to 0.001). Even 8 weeks after return to breathing air more arteries are muscularized than normal (for both alveolar wall and duct regions P chi 2 less than or equal to 0.001), and within the alveolar wall still more are muscularized than after hyperoxia (P chi 2 less than or equal to 0.001). Hyperoxia causes right ventricular hypertrophy, reducing the ratio of the weight of the left ventricle and septum to that of the right ventricle (P chi 2 less than or equal to 0.001). Weaning further increases the hypertrophy, the ratio being further reduced (P chi 2 less than or equal to 0.001, compared with both hyperoxia and control values). On return to breathing air the degree of hypertrophy is less, but it persists, and even after 8 weeks the ratio is still less than normal (P chi 2 less than or equal to 0.01).
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PMID:Oxygen toxicity and restructuring of pulmonary arteries--a morphometric study. The response to 4 weeks' exposure to hyperoxia and return to breathing air. 293 15

This study shows by morphometric and hemodynamic techniques that exposure to hyperoxia at normobaric pressure causes rapid structural remodeling of rat pulmonary arteries and pulmonary hypertension. After 7 days of 90% O2, pulmonary artery cross-sectional area is reduced by a striking loss of intraacinar arteries (control, 13 +/- 1 sq mm; exposed, 8 +/- 1 sq mm; P less than 0.001), the ratio of arteries to alveoli being 4:100 in control rats and 2.5:100 after hyperoxia. The lumen of preacinar and intraacinar arteries is narrowed by a reduction of vessel external diameter (ED) and an increased medial wall thickness (MT). There is a significant reduction in the percent medial thickness [( 2 X 100 X MT]/ED) in both regions. The proportion of muscular and partially muscular intraacinar arteries increases at the expense of nonmuscular ones (P [chi 2] less than 0.01), and fully muscular arteries appear in the alveolar wall where they are not normally found. Intimal thickening occurs in 19% of alveolar duct and 34% of alveolar wall nonmuscular arteries. Right ventricular hypertrophy occurs, the ratio of the left ventricle plus the septum to the right ventricle being significantly reduced (control, 4.07 +/- 0.26; exposed, 3.23 +/- 0.10; P less than 0.02). After 3 days of 87% O2, pulmonary artery pressure is still normal (17.0 +/- 0.9 mmHg) but after 7 days it is significantly increased (26.2 +/- 0.9 mmHg; P less than 0.01), as is pulmonary vascular resistance (control, 0.033 +/- 0.003; exposed, 0.065 +/- 0.015 U/kg; P less than 0.05). Return to air breathing (after 7 days at 87% O2) causes pulmonary vasoconstriction and a further rise of the pulmonary artery pressure (to 38.3 +/- 3.3 mmHg after 60 minutes).
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PMID:Pulmonary artery remodeling and pulmonary hypertension after exposure to hyperoxia for 7 days. A morphometric and hemodynamic study. 623 36

Pulmonary and intracardiac hemodynamic findings are reported. They were obtained by means of catheterization of right cardiac departments and the pulmonary artery with thermodilution in 57 patients with chronic nonspecific pulmonary diseases (CNPD), under conditions of resting, rationed bicycle-ergometric exercise, hypo- and hyperoxia, and nitroglycerin administration. Changes in pulmonary and intracardiac hemodynamics which reflect the ongoing exhaustion of compensatory mechanisms in the external respiration apparatus, the pulmonary vascular system and the heart, are shown to precede the formation of right ventricular hypertrophy in obstructive CNPD A classification of secondary pulmonary hypertension, based on clinical and instrumental signs, is offered.
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PMID:[Pulmonary hypertension in chronic nonspecific lung diseases]. 716 25

Young rats are thought to be more tolerant to hyperoxia. We propose that this may not be proven and depends on how tolerance is defined. We assessed oxygen tolerance in Sprague-Dawley rats from birth to maturity by comparing survival, lung water, antioxidant enzyme activity, lung morphometrics, heart weight, and arterial blood gases in newborn and 27-, 44-, 48-, and 96-day-old rats exposed to 100% O2 or room air for 22 days. Some 96-day-old rats (rest group) received only 50% O2 between 48 and 72 h. Mortality after 5 days of O2 was 0% in newborn and 27-day-old rats and 27% in 44-day-old rats but was > 80% in 48- and 96-day-old rats. Between 5 and 22 days, the death rate was 100% in newborns, 25% in 27-day-old rats, and 0% in 44- to 96-day-old rats. Death occurred when lung water was > 84% except in newborns, which tolerated high lung water for the first 7 days. In chronically exposed 44- and 96-day-old rats, lung water returned to normal. Enzyme activity increased with O2 at all ages but did not relate to survival. In 96-day-old rats, the initial increase was suppressed on day 3. All chronically O2-exposed rats had minimal nonvascular parenchymal changes but developed right ventricular hypertrophy and increased alveolar ductal artery muscularization and lost alveolar capillaries. The most mature rats were least affected. In O2, there was pulmonary insufficiency the first 3 days, followed by recovery, and later hypercarbia and decreased arterial PO2. We conclude that young rats, 0-44 days old, are more O2 tolerant for 5 days. More mature animals, surviving 5 days, are more tolerant to chronic exposure.
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PMID:Comparative age-related acute and chronic pulmonary oxygen tolerance in rats. 789 11

We investigated whether alpha 1-antitrypsin (alpha 1-AT) might protect neonatal rats from the pulmonary parenchymal and vascular effects resulting from hyperoxic exposure. Neonatal rats born into and maintained in hyperoxia (60% fraction of inspired oxygen) or room air were injected with a loading dose of alpha 1-AT (72 mg/kg) followed by 36 mg/kg every 72 h or with vehicle during the first 14 d of life. At the end of the experimental period, we measured body weight, lung compliance, lung volume, alveoli per mm2, and total number of alveoli and assessed right ventricular hypertrophy and vascular changes consisting of medial hypertrophy, muscular extension into peripheral, normally nonmuscular arteries, and number of peripheral arteries relative to alveoli. Our data show that alpha 1-AT treatment prevented the reduced lung compliance observed in the untreated hyperoxia-exposed neonatal rats, as well as the right ventricular hypertrophy and the associated vascular changes of medial hypertrophy of muscular arteries and muscularization of distal arteries. Reduced lung compliance in the hyperoxic but alpha 1-AT-untreated rats was associated with a reduction in lung elastin compared with room-air or alpha 1-AT-treated rats. In room-air rats, alpha 1-AT treatment increased lung compliance but also reduced the number of arteries relative to the number of alveoli, a feature that was not, however, associated with right ventricular hypertrophy. Our data suggest that supplemental alpha 1-AT might restore the imbalance in elastolytic activity induced by hyperoxia and thereby alleviate the toxic effects on lung parenchymal and vascular development.
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PMID:Alpha 1-antitrypsin protects neonatal rats from pulmonary vascular and parenchymal effects of oxygen toxicity. 789 85

Chronic hypoxia causes pulmonary hypertension, the mechanism of which includes altered collagen metabolism in the pulmonary vascular wall. This chronic hypoxic pulmonary hypertension is gradually reversible upon reoxygenation. The return to air after the adjustment to chronic hypoxia resembles in some aspects a hyperoxic stimulus and we hypothesize that the changes of extracellular matrix proteins in peripheral pulmonary arteries may be similar. Therefore, we studied the exposure to moderate chronic hyperoxia (FiO2 = 0.35, 3 weeks) in rats and compared its effects on the rat pulmonary vasculature to the effects of recovery (3 weeks) from chronic hypoxia (FiO2 = 0.1, 3 weeks). Chronically hypoxic rats had pulmonary hypertension (Pap = 26 +/- 3 mm Hg, controls 16 +/- 1 mm Hg) and right ventricular hypertrophy. Pulmonary arterial blood pressure and right ventricle weight normalized after 3 weeks of recovery in air (Pap = 19 +/- 1 mm Hg). The rats exposed to moderate chronic hyperoxia also did not have pulmonary hypertension (Pap = 18 +/- 1 mm Hg, controls 17 +/- 1 mm Hg). Collagenous proteins isolated from the peripheral pulmonary arteries (100-300 microm) were studied using polyacrylamide gel electrophoresis. A dominant low molecular weight peptide (approx. 76 kD) was found in hypoxic rats. The proportion of this peptide decreases significantly in the course of recovery in air. In addition, another larger peptide doublet was found in rats recovering from chronic hypoxia. It was localized in polyacrylamide gels close to the zone of alpha2 chain of collagen type I. It was bound to anticollagen type I antibodies. An identically localized peptide was found in rats exposed to moderate chronic hyperoxia. The apparent molecular weight of this collagen fraction suggests that it is a product of collagen type I cleavage by a rodent-type interstitial collagenase (MMP-13). We conclude that chronic moderate hyperoxia and recovery from chronic hypoxia have a similar effect on collagenous proteins of the peripheral pulmonary arterial wall.
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PMID:Hyperoxia and recovery from hypoxia alter collagen in peripheral pulmonary arteries similarly. 1152 43

We used a prematurely born rat/hyperoxia model of bronchopulmonary dysplasia (BPD) to test whether keratinocyte growth factor (KGF) treatment would protect against the development of several serious (cardio-)pulmonary complications of early life exposure to hyperoxia. KGF significantly protected against hyperoxic lethality (13-day survival rate = 50/64 (78%) for the O(2)-KGF vs. 29/66 (44%) for the O(2)-saline group, p < 0.001). Although KGF failed to protect against hyperoxic inhibition of normal postnatal alveoli formation and early pulmonary fibrosis, KGF consistently had a significant protective/preventive effect against the development of pulmonary hypertension during hyperoxia as reflected in comparative right ventricular hypertrophy: mean increase = +35% above normal for the O(2)-saline group vs. +3% for the O(2)-KGF premature rat group (p < 0.01).
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PMID:Protective effect of keratinocyte growth factor against lung abnormalities associated with hyperoxia in prematurely born rats. 1274 56

Exposure of newborn rats to hyperoxia impairs alveolarization and vessel growth, causing abnormal lung structure that persists during infancy. Recent studies have shown that impaired angiogenesis due to inhibition of vascular endothelial growth factor (VEGF) signaling decreases alveolar and vessel growth in the developing lung, and that nitric oxide (NO) mediates VEGF-dependent angiogenesis. The purpose of this study was to determine whether hyperoxia causes sustained reduction of lung VEGF, VEGF receptor, or endothelial NO synthase (eNOS) expression during recovery, and whether inhaled NO improves lung structure in infant rats after neonatal exposure to hyperoxia. Newborn rat pups were randomized to hyperoxia [fraction of inspired oxygen (Fio(2)), 1.00] or room air exposure for 6 d, and then placed in room air with or without inhaled NO (10 ppm) for 2 wk. Rats were then killed for studies, which included measurements of body weight, lung weight, right ventricular hypertrophy (RVH), morphometric analysis of alveolarization (by mean linear intercept (MLI), radial alveolar counts (RAC), and vascular volume (Vv), and immunostaining and Western blot analysis. In comparison with controls, neonatal hyperoxia reduced body weight, increased MLI, and reduced RAC in infant rats. Lung VEGF, VEGFR-2, and eNOS protein expression were reduced after hyperoxia. Inhaled NO treatment after hyperoxia increased body weight and improved distal lung growth, as demonstrated by increased RAC and Vv and decreased MLI. We conclude that neonatal hyperoxia reduced lung VEGF expression, which persisted during recovery in room air, and that inhaled NO restored distal lung growth in infant rats after neonatal hyperoxia.
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PMID:Inhaled nitric oxide enhances distal lung growth after exposure to hyperoxia in neonatal rats. 1587 97

Troponin T is a cardiac-specific protein forming part of the contractile apparatus of striated muscle, and in humans it is a new, sensitive and highly specific indicator of early myocardial damage in 'at risk' patients. Serum troponin T values were investigated in 7-day-old hypoxia- and hyperoxia-treated and 10-day-old ascitic and debilitated commercial broiler chicks. The results showed that there was a significant increase in troponin T values in the hypoxic chicks (P< 0.05) compared with their normoxic flockmates. There was also a small, but insignificant rise in the troponin T values of the hyperoxia-treated chicks. The results confirm previous studies that myocardial damage in these young chicks is associated with hypoxia and that the injury caused permits the measurement of troponin T released from the cardiomyocytes. Significant increases in troponin T were also measured in 10-day-old ascitic (P < 0.05) and debilitated (P < 0.02) broiler chicks compared with age-matched control broilers. In both age-groups of birds, the arterial pressure index, a measurement of right ventricular hypertrophy caused by chronic pulmonary hypertension, was similar with the respective control values and yet the troponin T concentrations were significantly different. These results demonstrate the importance of this assay in young broiler chickens as a marker of early myocardial damage in these birds. It is proposed that this assay for troponin T could be a valuable prognostic tool in future genetic selection programmes to reduce the degree of susceptibility to hypoxia and with it the incidence of ascites in young broilers.
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PMID:Serum troponin T values in 7-day-old hypoxia-and hyperoxia-treated, and 10-day-old ascitic and debilitated, commercial broiler chicks. 1864 90


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