Effects of high oxygen tension on the metabolism of vasoactive hormones in isolated perfused rat lungs

Toivonen, Heikki; Hartiala, Jaakko; Bakhle, Y.S.

doi:10.1111/j.1748-1716.1981.tb06723.x

Cited by 34 publications

(7 citation statements)

References 16 publications

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“…105,108,109 Harabin et al demonstrated that prolonged exposure to an F IO 2 of 1.0 decreases endothelial metabolism by 50% in dogs. 105 This accounts for pulmonary dysregulation of circulating vasoactive substances during hyperoxia 110 and partially explains subsequent pre-terminal hemodynamic instability. 105 Physiologic states associated with increased metabolism are known to enhance HALI, 79 probably because of elevated oxidative phosphorylation and increased mitochondrial ROS production.…”

Section: Overview Of the Molecular Biology Of Halimentioning

confidence: 99%

Hyperoxic Acute Lung Injury

2012

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Prolonged breathing of very high FIO2 (FIO2 ≥ 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of FIO2, is usually fatal. The severity of HALI is directly proportional to PO2 (particularly above 450 mm Hg, or an FIO2 of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts of reactive O2 species that overwhelms natural antioxidant defenses and destroys cellular structures through several pathways. Genetic predisposition has been shown to play an important role in HALI among animals, and some genetics-based epidemiologic research suggests that this may be true for humans as well. Clinically, the risk of HALI likely occurs when FIO2exceeds 0.7, and may become problematic when FIO2 exceeds 0.8 for an extended period of time. Both high-stretch mechanical ventilation and hyperoxia potentiate lung injury and may promote pulmonary infection. During the 1960s, confusion regarding the incidence and relevance of HALI largely reflected such issues as the primitive control of FIO2, the absence of PEEP, and the fact that at the time both ALI and ventilator-induced lung injury were unknown. The advent of PEEP and precise control over FIO2, as well as lung-protective ventilation, and other adjunctive therapies for severe hypoxemia, has greatly reduced the risk of HALI for the vast majority of patients requiring mechanical ventilation in the 21st century. However, a subset of patients with very severe ARDS requiring hyperoxic therapy is at substantial risk for developing HALI, therefore justifying the use of such adjunctive therapies.

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Section: Overview Of the Molecular Biology Of Halimentioning

confidence: 99%

Hyperoxic Acute Lung Injury

2012

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“…After exposure of rats to greater than 95% 0, for 50 h, pulmonary capillary surface area decreases to less than 25% of control [2]. Toivanen, Hartiola, and Bakhle [18] found a reversible decrease in conversion of angiotensin I to angiotensin 11 in isolated perfused lungs from rats exposed to hyperoxia for 48 h. Dobuler, Catravas, and Gillis [19] detected even earlier changes in lung ACE activity in rabbits exposed to hyperoxia in vivo. They reported a small but significant reduction in rabbit lung 3H-benzoyl-Phe-Ala-Pro hydrolysis after a 16-h oxygen exposure.…”

Section: Mk351a Binding Assaymentioning

confidence: 97%

“…Lung ACE activity decreases during hyperoxia exposure before any ultrastructural change is detected in the lung microvasculature [18,191. Hyperoxia causes cytopathic changes in lung endothelial cells and destruction of about 50% of lung capillaries after 3 days of oxygen exposure.…”

Section: Mk351a Binding Assaymentioning

confidence: 99%

Hypoxia-Induced Oxygen Tolerance: Maintenance of Endothelial Metabolic Function

Jackson

Ann

Oparil

1988

Experimental Lung Research

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Hypoxia (10%-12% O2) preadaptation for 4-7 days effectively protects rats from oxygen toxicity. The present study was designed to investigate the hypothesis that the lung's microvascular endothelium shares in development of oxygen tolerance and therefore that endothelial metabolic function would be protected from oxygen toxicity by prior adaptation to hypoxia. Since pulmonary oxygen toxicity decreases lung capillary angiotensin converting enzyme (ACE) activity, we assayed converting enzyme active sites in an isolated perfused rat lung preparation as a marker for the development of oxygen toxicity and tolerance. Rats were exposed to air, hypoxia (10% O2 for 4 days), hyperoxia (greater than 95% O2 for 2 days) alone, or hypoxia followed immediately by hyperoxia. Lung vascular ACE content was quantitated by measuring the single pass binding of an iodinated-converting enzyme inhibitor, 125I-MK351A, a derivative of lisinopril. Hypoxia adaptation per se had no effect on ACE content reflected in normal 125I-MK351A binding, whereas hyperoxia exposure caused a significant decrease in lung vascular ACE. Hyperoxia-induced decreases in ACE content were prevented partially by hypoxia adaptation, indicating that ACE content on luminal endothelial surfaces was protected from oxygen toxicity. In isolated perfused lungs 125I-MK351A binding reflects development of oxygen tolerance after hypoxia preadaptation and suggests that lung endothelial metabolic function is protected from oxygen toxicity.

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“…The early onset of this deficiency, 2h after treatment, suggests that it may be related to the early leukopaenia which results from sequestration of activated leukocytes in the pulmonary circulation. The activity of PGDH is readily inhibited by a hyperoxic environment (Parkes & Eling, 1975;Klein et al, 1978;Chaudhari et al, 1979;Toivonen et al, 1981) and the generation of oxygen-derived free radicals by activated leukocytes (Freeman & Crapo, 1982;Schraufstatter et al, 1984) may similarly serve to inactivate PGDH.…”

Section: Discussionmentioning

confidence: 99%

Modification by steroids of pulmonary oedema and prostaglandin E₂ pharmacokinetics induced by endotoxin in rats

Izumi

Bakhle

1988

British J Pharmacology

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1 A single i.p. injection of bacterial endotoxin in rats (3.5 mg kg ')caused lung injury assessed as changes in lung dry: wet weight ratio and leukopaenia over the subsequent 28 h.2 This treatment also slowed the efflux of 14C from [14C]-prostaglandin E2 (PGE2), i.e., increased t112 and increased the survival of PGE2 in isolated perfused lungs over the same period. 3 These effects of endotoxin were reversed by methylprednisolone (30mgkg 1), given 30min after the endotoxin. 4 Another synthetic corticosteroid, budesonide (1.2mg kg') given h before endotoxin partially prevented the lung injury and leukopaenia but did not affect the increased t,,2 for PGE2 nor its survival.5 The reversal by methylprednisolone of both the physical signs of lung injury and the changes in PGE2 pharmacokinetics caused by endotoxin suggests that changes in PGE2 pharmacokinetics could serve as an index of acute lung injury following sepsis.

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Effects of high oxygen tension on the metabolism of vasoactive hormones in isolated perfused rat lungs

Cited by 34 publications

References 16 publications

Hyperoxic Acute Lung Injury

Hyperoxic Acute Lung Injury

Hypoxia-Induced Oxygen Tolerance: Maintenance of Endothelial Metabolic Function

Modification by steroids of pulmonary oedema and prostaglandin E₂ pharmacokinetics induced by endotoxin in rats

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Effects of high oxygen tension on the metabolism of vasoactive hormones in isolated perfused rat lungs

Cited by 34 publications

References 16 publications

Hyperoxic Acute Lung Injury

Hyperoxic Acute Lung Injury

Hypoxia-Induced Oxygen Tolerance: Maintenance of Endothelial Metabolic Function

Modification by steroids of pulmonary oedema and prostaglandin E2 pharmacokinetics induced by endotoxin in rats

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Modification by steroids of pulmonary oedema and prostaglandin E₂ pharmacokinetics induced by endotoxin in rats