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

The current study traces the development of contractile cells in the nonmuscular segments of rat lung microvessels in hyperoxic pulmonary hypertension. New intimal cells first develop into a well-defined layer beneath the endothelium and internal to an elastic lamina. Ultrastructurally, these cells are found to be 1) fibroblasts recruited to the vessel wall from the interstitium and 2) intermediate cells, a population of preexisting vascular cells (structurally between a smooth muscle cell and a pericyte). Early in hyperoxia (days 3 through 7), interstitial fibroblasts migrate and align around the smallest vessels in which an elastic lamina is either absent or fragmentary. These cells then are incorporated into the vessel wall by tropoelastin secretion and the formation of an elastic lamina along their abluminal margin. After day 7, the new mural fibroblasts acquire the features of contractile cells, namely a basal lamina, extensive microfilaments, and dense bodies. In other vessels, as early as day 3 of hyperoxia, intermediate cells within the vessel intima begin to acquire the additional filaments and dense bodies of contractile cells. As hyperoxia continues, each cell pathway gives rise to vessels with distinct intimal or medial layers of contractile cells. In this way, thick-walled 'newly muscularized' vessel segments form adjacent to the capillary bed.
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PMID:Ultrastructural analysis of contractile cell development in lung microvessels in hyperoxic pulmonary hypertension. Fibroblasts and intermediate cells selectively reorganize nonmuscular segments. 146 6

Hypoxia is a known stimulant of pulmonary hypertension. We hypothesized graded effects of alveolar (PAO2) and arterial (PaO2) oxygen tension on pulmonary vascular resistance (PVR). A standard in situ, isolated lung preparation was modified by adding an oxygenator to the perfusion circuit with cannulation of the unarrested heart, allowing control of PAO2 and PaO2 in lungs devoid of ischemic injury. Seven anesthetized piglets were prepared with occlusive tracheostomy, ductus arteriosus ligation, and cannulation of the left atrium and main pulmonary artery. Animals were exsanguinated while simultaneously perfusing the lungs with a donor-blood primed extracorporeal membrane oxygenation circuit. Flow, left atrial pressure, pH, and PCO2 were kept constant. PAO2 and PaO2 were altered to establish four different experimental conditions as described by a latin square. PVR was calculated from measurements of pulmonary artery pressure (PAP) before and after introducing an experimental condition. Results show that (1) alveolar hypoxia significantly increases PVR despite arterial hyperoxia; (2) alveolar hypoxia is a more potent stimulus of pulmonary vasoconstriction than arterial hypoxemia; (3) alveolar and arterial oxygen tension are independent, additive effectors of PVR; and (4) recovery from acute hypoxic pulmonary vasoconstriction may be more sensitive to alveolar oxygen tension.
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PMID:Differential effects of alveolar and arterial oxygen tension on pulmonary vasomotor tone in ECMO-perfused, isolated piglet lungs. 203 Apr 77

Postadulticide pulmonary hypertension mechanisms and treatment with antihistamines and supplemental oxygen were studied in eight dogs with heartworm disease. To ensure severe postadulticide thromboembolism, additional heartworms (either 20 or 40 into 4 dogs each) were transplanted into naturally infected dogs before thiacetarsamide treatment. During pentobarbital anesthesia, 2 pulmonary hemodynamic studies were conducted on each dog with a sequence of baseline, hypoxia with FlO2 = 10%, hyperoxia with FlO2 = 100%, a second baseline, treatment with either diphenhydramine (D) or cimetidine (C), and another hypoxia. All dogs were pulmonary hypertensive, with each dog having a mean pulmonary arterial pressure (PPA) greater than 20 mm of Hg. Mean PPA increased from baseline conditions (25.0 +/- 4.5 SD for D and 24.3 +/- 4.4 for C) to hypoxia (28.5 +/- 4.7 for D and 28.4 +/- 3.7 for C), and decreased during hyperoxia (16.9 +/- 3.0 for D and 17.4 +/- 3.0 for C), respectively. Neither antihistamine reduced PPA at normoxia. The degree of pulmonary hypertension when breathing room air increased even more during hypoxia, and this increase was not attenuated by either antihistamine. Histamine did not appear to mediate pulmonary hypertension during postadulticide thromboembolism, nor to modify the hypoxia-mediated pulmonary hypertension at this disease stage. Because baseline PO2 was low (66.6 +/- 11.7 mm of Hg for D and 69.4 +/- 14.2 for C) and because PPA decreased during administration of oxygen, the pulmonary hypertension was mostly hypoxia-induced. In addition to the arterial lesions, much of the pulmonary hypertensive mechanism was an active and reversible vasoconstriction in response to hypoxia caused by the secondary lung disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postadulticide pulmonary hypertension of canine heartworm disease: successful treatment with oxygen and failure of antihistamines. 224 Jul 78

Rats injected with interleukin-1 (10 micrograms) and tumor necrosis factor (10 micrograms) and then exposed continuously to hyperoxia (greater than 99% O2, 1 atm) survived longer, had increased lung reduced/oxidized glutathione ratios, smaller pleural effusions, less pulmonary hypertension and improved arterial blood gases. The percentage of animals surviving for 72 hours in hyperoxia increased from 8% to 94%. Although relatively small increases in glutathione redox cycle enzymes occurred four and sixteen hours following cytokine injection, dramatic increases in all major antioxidant enzymes including superoxide dismutase, glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and catalase had occurred following 72 hours of exposure to hyperoxia. The protective effect of IL-1 + TNF against lethal pulmonary O2 toxicity could be partially inhibited by pre-injection of lysine acetylsalicylate or, less effectively, of ibuprofen. Recent studies have suggested that both IL-1 and TNF can induce manganese (mitochondrial) superoxide dismutase mRNA and protein synthesis in a variety of cell types. Preliminary studies suggest that IL-1 alone, in ample dosage, can provide protection against lethal pulmonary O2 toxicity. Future studies should be directed toward identification of acute phase changes in lung antioxidant enzymes, surfactant proteins and/or lipid components, enzymes needed for synthesis of surfactant phospholipids, and/or other protective proteins. Additional work also needs to be done in identifying the lung cell types in which early enzyme induction occurs. These studies should provide a better understanding of mechanisms whereby protection against pulmonary O2 toxicity can occur. An understanding of the molecular mechanisms inducing protective proteins should lead to more precise pharmacologic control of these processes.
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PMID:Protection against pulmonary oxygen toxicity by interleukin-1 and tumor necrosis factor: role of antioxidant enzymes and effect of cyclooxygenase inhibitors. 251 82

We evaluated the possible contributory role of hypoxia in the development of monocrotaline-induced pulmonary hypertension. Male Sprague-Dawley rats were injected subcutaneously with monocrotaline (60 mg/kg) or saline in controls and were kept in oxygen-enriched (inspired O2 fraction of 0.35) or compressed air chambers. After 21 days, rats were anesthetized while spontaneously breathing room air, hemodynamic parameters and arterial blood gases were measured, and animals were killed. Right ventricular peak systolic pressures (RVPP), right ventricular-to-left ventricular plus septal weight ratios (RV/LV + S), hematocrits, lung dry weight-to-body weight ratios, and medial thickness of pulmonary arteries were significantly reduced in monocrotaline-injected rats exposed to mild hyperoxia compared with air. The air-exposed monocrotaline-injected rats had significantly more arterial hypoxemia than the other groups, and mild hyperoxia had no effect on any of the measured variables in saline-injected rats. To determine whether the effects of mild hyperoxia occurred early or late after monocrotaline injection, we moved separate groups of rats from air to mild hyperoxia and vice versa 10 days after monocrotaline injection. After 21 days, significant reductions in RVPP and RV/LV + S occurred only in rats exposed to mild hyperoxia during the latter 11 days after injection. Our findings suggest that hypoxia contributes to the development of pulmonary hypertension relatively late after monocrotaline injection in rats but that it does not influence the early injury.
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PMID:Supplemental oxygen reduces right ventricular hypertrophy in monocrotaline-injected rats. 252 21

The labeling index (LI) of lung vascular intimal (endothelial and precursor smooth muscle, medial (smooth muscle), and adventitial cells (fibroblasts) was in the normal rat and in the rat with pulmonary hypertension caused by breathing high oxygen (87% O2 at normobaric pressure). Cell labeling was assessed during hyperoxia (Days 1, 4, 7, 10, and 28), at the start and end of weaning hyperoxia-adapted rats to air (Days 29 and 35), and 1, 2, and 4 wk after return to breathing air after hyperoxia and weaning (Days 42, 49, and 63). Bursts of intimal, medial, and adventitial cell proliferation different in their timing and extent contribute to lung vascular wall remodelling in these injuries. The Ll of the microvascular fibroblast increased most on Day 4 of hyperoxia (20-fold); it persisted above the normal rate throughout hyperoxia and was high at the start of weaning (greater than 1- less than 2-fold). Two weeks after return to breathing air, it again increased (less than 1-fold). The Ll of the microvascular endothelial cell increased most on Day 7 of hyperoxia (10-fold); it also persisted above the normal rate throughout hyperoxia and at the start of weaning (greater than 2- less than 3-fold) and increased again 2 wk after return to breathing air (6-fold). Labeled precursor cells were not present in the normal lung: they were present on Days 4 and 7 of hyperoxia but not at any other time, including weaning and return to breathing air.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lung vascular cell proliferation in hyperoxic pulmonary hypertension and on return to air: [3H]thymidine pulse-labeling of intimal, medial, and adventitial cells in microvessels and at the hilum. 281 15

Extracorporeal membrane oxygenation (ECMO) provides lung rest for moribund infants with congenital diaphragmatic hernia (CDH) after deterioration from a "honeymoon" period. This suggests that unstable pulmonary hypertension determines demise more than pulmonary hypoplasia. We avoided treating overwhelming pulmonary hypoplasia by using ECMO only if the premoribund condition had been marked by evidence of adequate lung parenchyma as a best preductal PO2 greater than 100 torr and PCO2 less than 50 torr with maximal therapy. Twenty-six CDH infants with respiratory distress within 4 hours survived operation. Five were not ECMO candidates, with best PO2 33 +/- 9, PCO2 157 +/- 30 torr, and died. Seven honeymoon infants, with best PO2 325 +/- 80, PCO2 27 +/- 5, survived without ECMO. Fourteen additional infants had honeymoon 26 +/- 13 hours with PO2 256 +/- 48, PCO2 30 +/- 8 followed by a-AdO2 gradients 600 torr x 16 +/- 4.5 hours despite maximal therapy. All 14 were treated with ECMO for 48 to 210 hours. Arterial blood gas values at initiation were PO2 34 +/- 6, PCO2 59 +/- 19, and pH 7.22 +/- 0.2. Right-to-left shunting due to pulmonary hypertension was documented by oximetry and two-dimensional echo/Doppler examination. Twelve of 14 (86%) ECMO-treated infants survived with normal arterial blood gas values on room air, no right-to-left shunting, and no gross neurologic sequellae to date. Two of 14 died. Improvement on ECMO was marked by positive hyperoxia response and decreased right-to-left shunting.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selective use of extracorporeal membrane oxygenation in the management of congenital diaphragmatic hernia. 312 55

Marked damage to the endothelium is associated with the pulmonary hypertension that develops during in vivo exposure to hyperoxia at normobaric pressures. We hypothesized that endothelial cell damage may contribute to initial increases in vascular tone during the development of hypertension by altering the metabolism of vasoactive compounds and/or modulating vessel responses to those agents that require an intact endothelium for their actions. This study reports the effects of in vivo hyperoxic damage to the lung on the pharmacologic properties of isolated pulmonary vessels. Proximal pulmonary arteries isolated from adult and weanling rats that breathed 85% O2 for 7 days were studied using myograph techniques. Isometric tension development was recorded in response to the cumulative addition of prostaglandin F2 alpha (PGF2 alpha) and the ability of acetylcholine (ACh) to relax precontracted vessels was subsequently assessed. Sensitivities to PGF2 alpha were increased in both adult and weanling hyperoxic vessels relative to control. Conversely, relaxation to acetylcholine was reduced following hyperoxic injury. Control vessels relaxed completely to acetylcholine addition, while only a 30% relaxation was recorded in adult hyperoxic arteries and a 50% relaxation was measured in weanling hyperoxic tissues. This effect on vasodilation was specific for the endothelium-dependent dilator ACh. By contrast, relaxation responses to sodium nitroprusside and papaverine, endothelium-independent agonists, were unaffected following hyperoxic injury. These results demonstrate that in vivo exposure to high O2 concentrations increases the sensitivity of isolated pulmonary arteries to the vasoconstrictor PGF2 alpha and markedly diminishes the ability of ACh to relax precontracted pulmonary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacologic properties of isolated proximal pulmonary arteries after seven-day exposure to in vivo hyperoxia. 320 69

Breathing 87% O2 for 7 days causes pulmonary vascular remodeling and pulmonary hypertension in the rat. In the isolated perfused lung of the normal and O2-exposed rat, change in pre- and postcapillary resistance was determined in response to challenge with angiotensin II (ANG II; 5, 25, and 50 micrograms) or histamine (0.5 and 1.0 microgram). In the hyperoxic lung both pre- and postcapillary resistance were increased at base line, although the latter less consistently so. In response to each agent precapillary resistance increased more than postcapillary resistance in the hyperoxic lung. In the normal lung pre- and postcapillary reactivity to histamine were similar but the latter was the greater in response to ANG II. In the hyperoxic lung only the pre- and postcapillary response to the first challenge of ANG II (5 micrograms) was greater than normal. The magnitude of the precapillary response was not related to the level of base-line resistance, and this response was significantly increased in a small number of hyperoxic lungs with base-line resistance in the normal range. Tachyphylaxis occurred after the first dose of ANG II. In the hyperoxic lung only the precapillary response to 0.5 micrograms histamine was greater than normal. We conclude that exposure to hyperoxia for 7 days causes an increase in pulmonary arterial reactivity. Furthermore, the alteration in reactivity is not caused by vascular restriction. We hypothesize that it is attributable to peripheral extension of smooth muscle in alveolar wall arteries.
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PMID:Pulmonary vascular reactivity in hyperoxic pulmonary hypertension in the rat. 321 63

Infants at risk for the development of persistent pulmonary hypertension of the newborn (PPHN) may require hyperventilation and muscle relaxation to improve lung compliance and oxygenation. During a 16-month period from June 1983 to October 1984, the author identified a separate population of infants who presented initially with symptoms indistinguishable from those of infants who develop severe PPHN, but who responded to hyperoxia (FiO2 = 1.00) and were successfully managed with supplemental oxygen without the need for intubation, hyperventilation, or muscle relaxation to achieve hypocarbic alkalosis and adequate oxygenation. We studied 20 infants, 15 with evidence of perinatal aspiration syndromes, and compared their initial responses to supplemental oxygen with those of 16 infants whose pulmonary hypertension was severe enough to require intubation, hyperventilation, and muscle relaxation for adequate control of oxygenation. No significant differences were noted in PaO2 response in FiO2 = 0.21 or 0.40. A significant rise in PaO2 was observed among infants with transient pulmonary vascular lability (TPVL), a milder form of pulmonary hypertension of the newborn, but not among infants with persistent pulmonary hypertension of the newborn, when exposed to FiO2 = 1.00 (250.7 torr versus 86.0 torr; P less than 0.0001). No significant differences in pH or PCO2 were observed. TPVL appears to present among term or post-term large-for-gestational age (LGA) infants, frequently delivered by cesarean section, who have experienced perinatal factors known to be associated with an increased risk of PPHN.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transient pulmonary vascular lability: a form of mild pulmonary hypertension of the newborn not requiring mechanical ventilation. 323 88


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