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

The effect of oxygen (O2) exposure on the ability of the isolated, perfused rat lung to clear serotonin (5-hydroxytryptamine, 5-HT) from the perfusate was evaluated in normal or vitamin E-deficient Sprague-Dawley rats. Rats were exposed to 100% O2 at 1 ATA for 4-48 h. Lungs were subsequently isolated, artificially ventilated, and perfused in a recirculating system with Krebs-Ringer bicarbonate solution, pH 7.4 containing 3% bovine serum albumin and 0.25 muM [14C] 5-HT. 5HT clearance was calculated from the disappearance rate of [ 14C] 5-HT from the perfusate. In normal rats exposed to 100% O2, there was a progressive reduction in the clearance of 5-HT with increasing duration of O2 exposure. Compared to lungs from air-exposed controls, clearance was depressed 20% (P less than 0.01) after 18 h, 22% (P less than 0.01) after 24 h, and 35% (P less than 0.001) after 48 h. With vitamin E-deficient rats, the reduction in 5-HT clearance occurred after a shorter exposure time and was of greater magnitude than in rats on a normal diet. Depression of 5HT clearance by the lungs is an early alteration of lung function fue to hyperoxia and is potentiated by vitamin E deficiency. The most likely mechanism for the depression of 5-HT clearance is interference with the transport properties of lung endothelium.
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PMID:Depression of serotonin clearance by rat lungs during oxygen exposure. 83 74

Neonatal rabbits were exposed to either normoxia (21% oxygen) or hyperoxia (. 95% oxygen) for 2-4 days, and isolated ventilated perfused lung preparations from the various animals were studied. 5-Hydroxytryptamine (5HT) uptake, perfusion pressure, alveolar lavage protein and lung tissue vitamin E concentrations were measured. There was no difference in mortality between the two groups at any time point. There was no difference in perfusion pressures at any time point. There were no differences between normoxic and hyperoxic animals in alveolar lavage protein or 5 HT uptake at 2 and 3 days. At 4 days, 5HT uptake (fractional) was lower in the hyperoxia group than in controls (0.65 +/- 0.033 v. 0.75 +/- 0.013 (mean +/- SE); p less than or equal to 0.05) and alveolar lavage protein was higher compared to normoxia (1111 +/- 415 micrograms/ml v. 481 +/- 78 micrograms/ml; p less than or equal to 0.05). Lung vitamin E concentrations were higher at 3 days in rabbits exposed to hyperoxia compared to normoxia (16.5 +/- 1.8 micrograms/gm v. 12.3 +/- 0.6 micrograms/gm; p less than or equal to 0.05). In air exposed animals there was a decrease in lung vitamin E concentration after 2 days, whereas hyperoxia exposed animals had no significant decrease in lung vitamin E concentrations from 2-4 days exposure. These studies establish that the decrease in 5HT uptake, albeit delayed compared to that described previously in adult animals, is a reasonable measure of pulmonary oxygen toxicity in newborn rabbits.
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PMID:Effect of hyperoxia on 5-hydroxytryptamine uptake by the neonatal rabbit lung. 182 Nov 73

The present study was undertaken to provide an improved environment in which to examine the capacity of more mature CNS tissue to survive following transplantation. Tissue containing serotonin (5-HT) neurons from nucleus raphe dorsalis of 4- and 8-week-old rats was transplanted to the anterior chamber of the eye. Baseline conditions were improved by minimizing the time of the grafting procedure and enhancing the nutrition and oxygenation of the grafting medium. Additional treatment of the grafts during the 4 weeks of in oculo development included either: (1) intermittent hyperbaric oxygen (HBO), (2) continuous hyperoxia, or (3) control. In vivo measurement revealed that all grafts decreased significantly in size, a majority of which still demonstrated a small degree of vascularization. Microscopically, a significant percentage of the grafts demonstrated 5-HT-immunoreactive (5-HT-ir) fiber outgrowth into the host irides, although 5-HT-ir cell bodies could not always be discerned. In terms of percentage of grafts with surviving 5-HT-ir fibers, the best results were seen with the grafts treated with continuous hyperoxia (3 out of 4), as compared to HBO-treated grafts (4/18) and the control group (3/24). For both the HBO-treated and control groups, slightly better results were seen with 4-week-old vs 8-week-old donor tissue. The density and the surface area covered by the 5-HT-ir fibers was not correlated with either treatment or donor age. Thus, while continuous hyperoxia or HBO treatment may have a positive effect, the enhanced baseline conditions appear to provide an environment in which to demonstrate that 5-HT neurons from 4- and 8-week-old rats possess the capacity to survive transplantation.
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PMID:Survival of adult 5-HT neurons following intraocular transplantation. 271 86

The contractile effects of 19 factors on isolated human arterial segments at term pregnancy were quantified, and 14 contractile agents were similarly applied to preterm (23 to 35 weeks) umbilical arteries. Responses to potassium chloride were used to normalize the data. At comparison with the term vessel, the preterm artery contracted more to angiotensin II and arachidonic acid and was more sensitive to oxytocin. Contractions were greater in term arteries to vasopressin, norepinephrine, prostaglandin D2, and prostaglandin E2 but similar in both group of arteries to bradykinin, histamine, acetylcholine, and prostaglandin F2 alpha. Neuropeptide Y, linoleic acid, uridine triphosphate, and thrombin were ineffective. Hyperoxia inconsistently induced weak, short-lived contractions. Contractions to cooling manifested marked desensitization and tachyphylaxis. Serotonin was the only agonist that displayed the pharmacodynamic features most likely to be important for closure: potency, efficacy, and long duration of action (greater than 2.5 hours). It was postulated that cellular elements surrounding umbilical vessels are primary sources of vasoactive agents that are important to closure of the fetoplacental circulation at birth.
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PMID:Pharmacodynamic study of maturation and closure of human umbilical arteries. 291 87

We assessed the changes in argyrophil neuroendocrine (NE) cell numbers, intensity of 5-HT fluorescence, and arterial medial thickness in the lungs of neonatal rabbits under various oxygen treatments. NE cell numbers and 5-HT fluorescence in normoxic rabbits increased from 12 hr before to 1 day after birth, and NE cells declined thereafter to the 10th day. In acute hypoxic (520 mm Hg for 2-2.5 hr) 5-day-old rabbits, 5-HT fluorescence was decreased, whereas NE cell numbers and medial thickness were unchanged. Neonates hypoxic from birth had higher NE cell numbers and increased medial thickness at 3 and 5 days, whereas 5-HT fluorescence was decreased compared with that in normoxic controls. These chronically hypoxic neonates showed a dramatic drop in argyrophil NE cell numbers to below normal when they were exposed to normoxia for 1 hr, but cell numbers and medial thickness returned to normal at 4 and 24 hr, respectively. We also tested the effect of acute and chronic hyperoxia: 100% O2 for 2-2.5 hr caused a significant drop in detectable NE cell numbers, whereas 40% O2 in N2 caused no change; chronic 40% O2 in N2 caused a fivefold increase in argyrophil NE cells by day 5, and medial thickness was below normal; 5-HT fluorescence decreased in acute 100% and chronic 40% hyperoxia and was elevated in acute 40% O2.
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PMID:Dynamics of the neuroendocrine cell--regulatory peptide system in the lung. Specific overview and new results. 618 8

To evaluate whether alpha-naphthylthioura (ANTU) protects against hyperoxic injury to the pulmonary endothelium, we monitored survival and serotonin uptake by the lungs of ANTU-treated rats (5 mg/kg) and Tween 80-treated control rats exposed to 100% O2 or air at 1 atmosphere absolute. Exposure to 100% O2 for 24 h or 48 h significantly depressed serotonin uptake in control rats. Serotonin uptake in ANTU-treated rats compared with that in control rats exposed to air for 24 or 48 h was also significantly depressed. However, serotonin uptake by the lungs of ANTU-treated rats exposed to 100% O2 for 48 h was significantly greater than uptake by control lungs similarly exposed to O2. Nine of 14 ANTU-treated rats were alive after 7 days of exposure to 100% O2, and serotonin uptake by the lungs of survivors had returned to control values (3.29 +/- 0.25). In contrast, only 1 of 14 control rats survived and serotonin uptake was 1.17 in this lone survivor. These results indicate that ANTU injuries pulmonary endothelial cells but protects against subsequently hyperoxic injury. This protection may account for the reduced mortality in ANTU-treated rats exposed to hyperoxia.
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PMID:Alpha-naphthylthiourea (ANTU) protects against hyperoxic depression of pulmonary serotonin uptake. 621 77

Platelets and serotonin (5-HT) have been increasingly implicated in the pathophysiological response to lung microvascular injury. These experiments were undertaken to study the effect of agents known to injure the pulmonary microvasculature on platelet function, i.e., 5-HT uptake kinetics. Mice were exposed to 100% normobaric oxygen (24 to 96 hr) or pretreated ip (3 to 24 hr) with paraquat dichloride (50 mg/kg), diquat dibromide (68 mg/kg), or alpha-naphthylthiourea (ANTU, 10 mg/kg). Mouse platelet 5-HT accumulation was described by a saturable uptake system, possessing high affinity and low capacity, acting in conjunction with passive diffusion. The kinetic constants for the saturable uptake system in control mice were Km 3.37 +/- 0.32 X 10(-7) M and Vmax 46.7 +/- 3.5 pmol 10(8) platelets-1 min-1. Exposure to oxygen for 24 hr resulted in an increased affinity, Km 1.91 +/- 0.67 X 10(-7) M, and a decreased Vmax, 20.0 +/- 5.0 pmol 10(8) platelets-1 4 min-1, with no change in the passive diffusion component. Pretreatment with paraquat (3 hr) produced similar changes (Km 1.71 +/- 0.27 X 10(-7) M and Vmax 15.8 +/- 1.6 pmol 10(8) platelets-1 4 min-1), while diquat and ANTU failed to alter the kinetics of platelet 5-HT uptake. These changes appeared to require a pulmonary toxicant capable of generating a flux of oxygen radicals, and were not due to either the presence of residual toxicant, the presence of an endogenous inhibitor in platelet-rich plasma, or changes in the platelet content of endogenous 5-HT. This study has shown that hyperoxia and paraquat affect platelet function, and suggests that this alteration may contribute to the pathophysiological response of the pulmonary microvasculature to injury produced by these agents.
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PMID:Hyperoxia and paraquat alter the kinetics of platelet serotonin uptake. 643 84

Exposure of mice to normobaric 100% oxygen for 24-96 h is known to damage the pulmonary capillary endothelium and alter the disposition of serotonin (5-hydroxytryptamine, 5-HT). We now report that such exposure increased the concentration of platelets and decreased the platelet content of 5-HT and a tracer dose of [3H]5-HT. After 48 h of hyperoxia exposure, the platelet concentration was elevated to 121% of air-exposed control values and the content of 5-HT and [3H]5-HT/10(9) platelets was decreased 76% and 57%, respectively. Kinetic analysis of the platelet 5-HT uptake process indicated that hyperoxia exposure caused an increased affinity and decreased velocity of transport. After 48 h of oxygen exposure the Km for platelet 5-HT uptake was 1.91 +/- 0.67 X 10(-7) M and the Vmax 30.1 +/- 4.6 pmol/10(8) platelets/4 min compared to air-exposed control values of Km 3.37 +/- 0.32 X 10(-7) M and Vmax 46.7 +/- 3.5 pmol/10(8) platelets/4 min, respectively. These changes in platelet 5-HT uptake and disposition may contribute to the pathophysiology of the pulmonary microvascular response to hyperoxia-induced injury.
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PMID:Hyperoxia alters platelet disposition of serotonin. 647 16

Lungs accumulate 5-hydroxytryptamine (serotonin, 5-HT) from the perfusate by a sodium-dependent, energy-requiring, saturable process. The rate-limiting step for uptake is the transport of 5-HT and not its subsequent metabolism to 5-hydroxyindoleacetic acid. Autoradiographic studies indicate that the pulmonary endothelium is the cellular site of uptake. The effect of hyperoxia on lung clearance of 5-HT was studied with isolated perfused and ventilated lungs from rats that were previously exposed to hyperoxia. Lungs were perfused with recirculating electrolyte solution and initial [5-HT] of 0.24 microM. The calculated fractional 5-HT clearance (fracion of 5-HT removed in a single pass) ws 0.77 +/- 0.02 (mean +/- SE: n = 44) for control rats. Mean fractional clearance decreased by 20% in rats exposed to 1 atm O2 for 18 hr and 30% after 4 atmospheres absolute (ata) O2 for 1 hr (p < 0.05). The effects of O2 at 4 ata were in part reversed by exposure to air for 3.5 hr and in part prevented by injection of superoxide dismutase (60 nmole/kg body weight). This degree of O2 exposure at either 1 or 4 ata had no effect on lung content of adenine nucleotides or the distribution of 3H-5HT on autoradiography. Rats maintained for 6 weeks on a vitamin E-deficient diet showed an increased effect of hyperoxia on 5-HT clearance and did not show reversal of changes after 24 hr of air breathing. The results indicate that exposure to elevatd po2 results in reversible depression of pulmonary 5-HT clearance that is potentiated by vitamin E deficiency. This suggests alteration of pulmonary endothelial membrane transport properties due to O2 toxicity.
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PMID:Environmental influences on uptake of serotonin and other amines. 740 97

There has been suggestion of a possible relationship between the intake of the appetite suppressant dexfenfluramine and the development of primary pulmonary hypertension. We investigated the pulmonary vascular effects of acute intravenous dexfenfluramine in pentobarbital-anesthetized dogs ventilated in hyperoxia (fraction of inspired oxygen, FIO2, 0.4) and either challenged with a FIO2 of 0.1 to induce hypoxic pulmonary hypertension (n = 20) or given autologous blood clots to induce embolic pulmonary hypertension (n = 6). Pulmonary vascular tone was evaluated by multipoint (mean pulmonary artery pressure [Ppa] - pulmonary artery occluded pressure [Ppao])/cardiac output (Q) plots. Hypoxia increased Ppa - Ppao over the entire range of Q studied, from 1.5 to 4.0 L/min/m2, in 12 dogs (responders) and had no significant effect on (Ppa - Ppao)/Q plots in 8 other dogs (nonresponders). Dexfenfluramine did not affect (Ppa - Ppao)/Q plots in 6 responders but shifted (Ppa - Ppao)/Q plots to higher pressures in hypoxia in 6 nonresponders (p < 0.001). Dexfenfluramine had no effect on (Ppa - Ppao)/Q plots in the 6 dogs with embolic pulmonary hypertension. Because dexfenfluramine has serotoninergic properties, we compared the effects of ketanserin, a serotonin (5-hydroxytryptamine, 5-HT) S2 receptor antagonist, on naturally present versus dexfenfluramine-restored hypoxic pulmonary vasoconstriction. Ketanserin did not affect hyperoxic or hypoxic pulmonary vascular tone, neither in 6 responders nor in 2 nonresponders with dexfenfluramine-restored hypoxic vasoconstriction. We conclude that dexfenfluramine restores hypoxic pulmonary vasoconstriction in dogs with weak or absent hypoxic pressor response and that this effect is unlikely to be mediated by activation of 5-HT S2 receptors.
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PMID:Effects of dexfenfluramine on hypoxic pulmonary vasoconstriction and embolic pulmonary hypertension in dogs. 788 58


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