Effect of Platelet-activating Factor Receptor Antagonism on Endotoxin-induced Lung Dysfunction in Awake Sheep

Christman, Brian W.; Lefferts, Peter L.; Blair, Ian A.; Snapper, James R.

doi:10.1164/ajrccm/142.6_pt_1.1272

Cited by 36 publications

(32 citation statements)

References 15 publications

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“…An exaggerated vasoconstrictor response of PAs in ARDS/ ALI is important as it may contribute to increased pulmonary vascular resistance, pulmonary hypertension, and lung edema (4,6). Other authors have found increased sensitivity to HPV in perfused lungs from endotoxin-treated rats (12,18), in isolated PA exposed in vitro to endotoxin (16), or in the isolated blood-perfused rat lung after treatment with TNF-α (15).…”

Section: Discussionmentioning

confidence: 99%

“…Pulmonary vascular dysfunction is a known feature of ARDS/ALI. Pulmonary vascular resistance and pulmonary arterial pressure are elevated in patients with ARDS (4) and in animal models of ALI induced by sepsis/endotoxin (5,6) or HVt ventilation (7). Another key feature of ARDS/ ALI is the mismatch of ventilation and perfusion leading to Pulmonary Vascular Dysfunction Induced by High Tidal Volume Mechanical Ventilation* intrapulmonary shunting due to an impaired hypoxic pulmonary vasoconstriction (HPV) (8), which contributes to the systemic hypoxemia in ARDS/ALI (9,10).…”

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confidence: 99%

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Pulmonary Vascular Dysfunction Induced by High Tidal Volume Mechanical Ventilation*

Menéndez¹,

Martínez-Caro²,

Moreno³

et al. 2013

Critical Care Medicine

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pulmonary Vascular Dysfunction Induced by High Tidal Volume Mechanical Ventilation*

Menéndez¹,

Martínez-Caro²,

Moreno³

et al. 2013

Critical Care Medicine

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“…Furthermore, endotoxin infusion causes an increase in the levels of PAF [29]. Pretreatment with PAF antagonists inhibits both the rise in TXA 2 and the pulmonary pressor response to endotoxin [30].…”

Section: Discussionmentioning

confidence: 99%

Pathophysiology and pharmacological treatment of pulmonary hypertension in acute respiratory distress syndrome

Moloney

Evans²

2003

Eur Respir J

115

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Pulmonary hypertension (PH) is a characteristic feature of the acute respiratory distress syndrome (ARDS). The magnitude of PH has been shown to correlate with the severity of lung injury in patients with ARDS independently of the severity of associated hypoxaemia and has an adverse prognostic significance.Early in the histopathological evolution of ARDS, pulmonary vasoconstriction, thromboembolism and interstitial oedema contribute to the development of PH, although pulmonary vascular remodelling probably occurs eventually. Intravenous vasodilator agents lead to an increase in intrapulmonary shunting and systemic hypotension, which can limit their therapeutic use, and have not been shown to improve survival. By contrast, rapidly metabolised vasodilators administered by inhalation induce selective pulmonary vasodilatation and decrease shunting, but again do not appear to confer a survival benefit.Research aimed at further understanding the mechanisms that underlie pulmonary hypertension, a characteristic feature of the acute respiratory distress syndrome, are expected to provide improvements in pharmacological interventions for the treatment of pulmonary hypertension in the acute respiratory distress syndrome.

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“…10 Briefly, 2 ng of tetradeuterated thromboxane B 2 was introduced into 100 L of each sample as an internal standard. Samples were acidified with 0.5% formic acid and extracted with ethyl acetate.…”

Section: Analytical and Statistical Methodsmentioning

confidence: 99%

Intravascular Source of Adenosine During Forearm Ischemia in Humans

et al. 1999

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Abstract-It is believed that adenosine is released in ischemic tissues and contributes to reactive hyperemia. We tested this hypothesis in the human forearm using microdialysis to estimate interstitial and intravascular levels of adenosine and caffeine withdrawal to potentiate endogenous adenosine and determine its effect on reactive hyperemia. Forearm blood flow response to ischemia was measured by air plethysmography before and 60 hours after the last dose of caffeine (250 mg TID for 7 days, nϭ6). Forearm blood flow increased by 274Ϯ66% and 467Ϯ97% after 3 minutes of forearm ischemia, before and during caffeine withdrawal, respectively (PϽ0.05). Thus, caffeine withdrawal enhances reactive hyperemia. To determine the source of adenosine, we measured interstitial adenosine with the use of a microdialysis probe inserted into the flexor digitorum superficialis muscle of the forearm, and we measured intravascular adenosine with the use of a microdialysis probe inserted retrogradely into the medial cubital vein. Dialysate samples were collected at 15-minute intervals during resting, forearm ischemia, and recovery periods. Forearm ischemia failed to increase muscle dialysate concentrations of adenosine but did increase intravascular dialysate adenosine 2.1-fold, from 0.61Ϯ0.12 to 1.28Ϯ0.39 mol/L (PϽ0.01, nϭ8). Intravascular dialysate concentrations of thromboxane B 2 did not increase during ischemia, ruling out platelet aggregation as a source of adenosine. These results support the hypothesis that endogenous adenosine contributes to reactive hyperemia and indicate that the major source of adenosine in the human forearm is intravascular. We speculate that endothelial cells are the source of intravascular adenosine during ischemia. (Hypertension. 1999;33:1453-1457.)Key Words: adenosine Ⅲ ischemia Ⅲ muscle Ⅲ microdialysis L ocal vasodilation is an important protective response to ischemia. This reactive hyperemia, present in all vascular beds with the exception of the kidneys, is largely due to metabolic factors produced by the mismatch between oxygen supply and metabolic demand. Adenosine has been identified as one of the metabolic products involved in this process. The contribution of adenosine to reactive hyperemia has been extensively studied in coronary circulation, 1 and adenosine has also been proposed to contribute to blood flow regulation in several other vascular beds, including skeletal muscle. [2][3][4] Because the actions of adenosine are mediated by cell membrane receptors, its importance in modulating reactive hyperemia will be proportional to the extracellular concentrations it reaches during ischemia. Adenosine is released in tissues when metabolic demands exceed oxygen supply, but extracellular concentrations are limited by efficient mechanisms of cellular uptake and metabolism. Cellular uptake is particularly potent in humans and accounts for the extremely short half-life of adenosine in blood, estimated at Ͻ1 second. 5 Previous attempts to assess how much of an increase in extracellular adenosine is...

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Effect of Platelet-activating Factor Receptor Antagonism on Endotoxin-induced Lung Dysfunction in Awake Sheep

Cited by 36 publications

References 15 publications

Pulmonary Vascular Dysfunction Induced by High Tidal Volume Mechanical Ventilation*

Pulmonary Vascular Dysfunction Induced by High Tidal Volume Mechanical Ventilation*

Pathophysiology and pharmacological treatment of pulmonary hypertension in acute respiratory distress syndrome

Intravascular Source of Adenosine During Forearm Ischemia in Humans

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