An Imbalance between the Excretion of Thromboxane and Prostacyclin Metabolites in Pulmonary Hypertension

Christman, Brian W.; McPherson, Charles D.; Newman, John H.; King, Gayle; Bernard, Gordon R.; Groves, Bertron Μ.; Loyd, James E.

doi:10.1056/nejm199207093270202

Cited by 1,079 publications

(639 citation statements)

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“…This suggests that the imbalance in prostanoids is involved in the development and persistence of pulmonary hypertension. It is assumed that endothelial damage which is inevitably accompanied by remodeling or organic change causes a deterioration ofPGI2 production in patients with pulmonary hypertension, as the vascular beds in pulmonaryarteries and/or arterioles are considered to be the main sites producing PGI2 (1)(2)(3)(4)(5). However, it has not been clearly determined whether pulmonary vascular beds responsible for the production of PGI2are functionally preserved or not in OSAS.Sheer stress in pulmonary vascular beds can be observed in various kinds of physiological and pathological situations such as hypoxic pulmonary vasoconstriction (HPV) and increased cardiac output.…”

Section: Discussionmentioning

confidence: 99%

“…It is well recognized that thromboxane A2 (TxA2) is a vasoconstrictor as well as a potent stimulus for platelet aggregation which can be antagonized by the vasodilator prostacyclin (PGI2) (1)(2)(3)(4)(5). It is also suggested thatthere is apathophysiological link between systemic hypertension and obstructive sleep apnea syndrome (OSAS) (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…However, the role of the metabolism ofprostanoids in OSASremains elusive. Christman et al have reported that there is an increase in the 24-hour excretion of TxA2as well as a decrease in that of prostacyclin in the primary as well as in the secondary form of pulmonary hypertension (3), suggesting that the imbalance in the release of these prostanoids is involved in the development and persistence of pulmonary hypertension.…”

Section: Introductionmentioning

confidence: 99%

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Compensatory Excretion of Prostacyclin and Thromboxane Metabolites in Obstructive Sleep Apnea Syndrome.

et al. 1998

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Since obstructive sleep apnea syndrome (OSAS) is often linked with systemic hypertension, we sought to clarify the characteristics ofprostanoid metabolism in OSAS. In 7 OSASpatients (apneahypopnea index, 51.0 ± 23.4) and 7 non-snorers as control, nocturnal urine was sampled and analyzed for stable metabolites of prostacyclin (PGI2) and thromboxane A2 (TxA2), [6-keto-PGFlot and thromboxane B2 (TxB2)]. The ratio of 6-keto-PGFl0C to TxB2 was significantly higher in OSAS (2.97 ± 1.52) than in control (1.38 ± 0.38). Successful treatment with nasal continuous positive airway pressure (8.3 ± 1.5 cmH2O)for 3 days caused a significant decrease in mean blood pressure in OSAS. Moreover, the 6-keto-PGFl0C to TxB2 ratio also significantly decreased to 1.74 ± 0.58, a level which may not significantly different from control. These results suggest that the production ratio of PGI2 to TxA2is shifted toward vasodilatation in untreated OSAS. Weconclude that the production of prostanoids plays a role in compensating for the systemic hypertension in OSAS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Compensatory Excretion of Prostacyclin and Thromboxane Metabolites in Obstructive Sleep Apnea Syndrome.

et al. 1998

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“…Recent studies have reported encouraging results with the use of repeated infusions of prostaglandin in primary pulmonary hypertension (14), but the efficacy of this approach is still uncertain, and there is insufficient experience to determine optimum therapy in secondary cases. The response to prostacyclin may, however, implicate different pressor mechanisms operating in the pulmonary and systemic circulations (15).…”

Section: Discussionmentioning

confidence: 99%

A fatal pulmonary complication of lupus in pregnancy

Rubin

Geran

Rose

et al. 1995

Arthritis & Rheumatism

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Pulmonary vasculitis is an uncommon complication of systemic lupus erythematosus (SLE), and has not been previously documented in pregnancy. This case report describes the rapidly fatal course of a pregnant SLE patient, whose terminal illness was manifested by severe pulmonary hypertension and unexpected autopsy findings of medium and large vessel vasculitis. The relationship of these unusual manifestations to other clinical and serologic features of SLE, as well as novel therapeutic options, are discussed.Pulmonary involvement is reported to occur in up to 50% of patients with systemic lupus erythematows (SLE) at some time during the course of their illness (1). Pleuritis is the most frequent presenting complaint, yet pulmonary parenchymal involvement is uncommon. Pulmonary hypertension has been documented since 1981 (2-5) and is often associated with Raynaud's phenomenon, digital vasculitis, and livedo (3,4). The diagnosis of pulmonary hypertension is frequently delayed, and the development of this complication is not necessarily related to the severity of the overall lupus activity; therefore, a high index of suspicion is required (4). Response to standard therapy is generally unpredictable and often disappointing (4,6).The case presented here is that of a pregnant woman with SLE and pulmonary hypertension, whose course was complicated by the development of severe pulmonary vasculitis. It is impossible to determine with certainty whether this latter complication was directly attributable to the patient's underlying SLE or was somehow precipitated by the terminal phases of her pregnancy. In view of the generally unsatisfactory

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“…Prostacyclin production appears to increase in late gestation and early postnatal life [65,66], indicating its importance in promoting the neonatal pulmonary vascular transition. Pulmonary hypertension in both neonates and older children is characterized by an decrease in the biosynthesis of prostacyclin accompanied by increased synthesis of the vasoconstrictor thromboxane A 2 [67]. Furthermore, the PGI 2 receptor (IP) is decreased in adult and pediatric patients with pulmonary hypertension, and animal studies point to its contribution to altered vasodilation in PPHN [68].…”

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confidence: 99%

Pharmacotherapy of Pulmonary Hypertension

2013

Handbook of Experimental Pharmacology

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Pulmonary arterial hypertension is a serious disease with significant morbidity and mortality. While it can occur idiopathically, it is more commonly associated with other cardiac or lung diseases. While most of the available therapies were tested in adult populations, and most therapies in children remain off-label, new reports and randomized trials are emerging that inform the treatment of pediatric populations. This review discusses currently available therapies for pediatric pulmonary hypertension, their biologic rationales, and evidence for their clinical effectiveness. KeywordsPulmonary hypertension; Pulmonary vasculature; Vasodilator; Nitric Oxide; Phosphodiesterase; Prostacyclin; Endothelin NORMAL PULMONARY VASCULAR TRANSITIONDuring fetal life, the placenta serves as the organ of gas exchange, and the fetal circulation uses a series of adaptive mechanisms to maximize delivery of oxygen to metabolically active organs such as the brain, gut and kidney. The most highly oxygenated blood enters the fetus via the umbilical vein. To efficiently direct oxygenated blood to the systemic circulation and minimize oxygen loss, almost 90% of fetal blood flow is diverted past the lungs through anatomic shunts through the foramen ovale and the ductus arteriosus. While the lung rapidly grows its network of small pulmonary arteries during the second half of gestation [1], blood flow in the pulmonary circulation remains highly restricted by hypoxic pulmonary vasoconstriction of small pulmonary arteries, which is reversed at birth by the sudden increase in lung oxygenation when the newborn takes his or her first breath. After birth, the first few breaths induce a rapid decrease in pulmonary vascular resistance and increase in pulmonary vascular flow in response to lung expansion, increased oxygen tension, and increased pH. Pulmonary artery pressure and vascular resistance decrease more slowly, with pulmonary arterial pressure reaching its nadir ~2-3 weeks after birth. However, the responsiveness to hypoxia is retained into adulthood, and pulmonary hypertension can be easily triggered in the newborn period by hypoxic lung disease, apnea, or other causes.© 2012 Elsevier Inc. All rights reserved. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptPediatr Clin North Am. Author manuscript; available in PMC 2013 October 01. DEFINITION AND CLASSIFICATION OF PEDIATRIC PULMONARY HYPERTENSIONPulmonary hypertension is necessary to support gas exchange in the fetus, but if pulmonary arterial pressure is elevated after birth or during infancy or childhood,...

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An Imbalance between the Excretion of Thromboxane and Prostacyclin Metabolites in Pulmonary Hypertension

Cited by 1,079 publications

References 27 publications

Compensatory Excretion of Prostacyclin and Thromboxane Metabolites in Obstructive Sleep Apnea Syndrome.

Compensatory Excretion of Prostacyclin and Thromboxane Metabolites in Obstructive Sleep Apnea Syndrome.

A fatal pulmonary complication of lupus in pregnancy

Pharmacotherapy of Pulmonary Hypertension

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