Postinjury Thromboxane Receptor Blockade Ameliorates Acute Lung Injury

Goff, Charles D.; Corbin, Richard; Theiss, Steven D.; Frierson, Henry F.; Cephas, Gerald A.; Tribble, Curtis G.; Krön, Irving L.; Young, Jeffrey S.

doi:10.1016/s0003-4975(97)00490-6

Cited by 32 publications

(24 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Once they adhere to the vascular endothelium and activate their interaction with neutrophils [40] that produces endothelial and epithelial injury increasing vascular permeability [41] that leads to fluid and protein accumulation in the alveoli. We found a significant association between the use of antiplatelet therapy and a decreased incidence of ARDS-ALI.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Severe Sepsis and Septic Shock Patients on Chronic Antiplatelet Treatment: A Historical Cohort Study

Valerio-Rojas

Jaffer

Kor

et al. 2013

Critical Care Research and Practice

View full text Add to dashboard Cite

Background. Sepsis is characterized by dysfunctional activation of platelets, and antiplatelet therapy could improve the outcomes of septic patients. Methods. We performed a retrospective cohort study of severe sepsis or septic shock adult patients. Outcomes of patients on antiplatelet therapy were compared to those that were not taking antiplatelet therapy by univariate analysis followed by a propensity score analysis based on the probability of receiving antiplatelet therapy. Results. Of 651 patients included in the study 272 (42.8%) were on antiplatelet therapy before the development of severe sepsis or septic shock. After adjusting for important confounding variables antiplatelet therapy was not associated with a decreased risk of hospital mortality (odds ratio 0.73, 95% confidence interval 0.46–1.16). Antiplatelet therapy was associated with a decreased incidence of acute respiratory distress syndrome/acute lung injury (odds ratio 0.50, 95% confidence interval 0.35–0.71) and reduced need of mechanical ventilation (odds ratio 0.62, 95% confidence interval 0.45–87). Incidence of acute kidney injury was similar between both groups (odds ratio 1.08, 95% confidence interval 0.73–1.59). Conclusions. The use of antiplatelet therapy before the diagnosis of severe sepsis or septic shock was not associated with decreased hospital mortality. Antiplatelet therapy was associated with a decreased incidence of acute lung injury/acute respiratory distress syndrome.

show abstract

Section: Discussionmentioning

confidence: 99%

Outcomes of Severe Sepsis and Septic Shock Patients on Chronic Antiplatelet Treatment: A Historical Cohort Study

Valerio-Rojas

Jaffer

Kor

et al. 2013

Critical Care Research and Practice

View full text Add to dashboard Cite

show abstract

“…Thrombin as well as thromboxane A2 (which is produced by lung tissue) activate platelets, which leads to a broad range of cellular responses that may contribute to the development of lung injury [65]. Subsequently, platelet-neutrophil interactions play an important role in the recruitment of neutrophils into the lungs during lung injury and ARDS [66].…”

Section: Interactions Between Bronchoalveolar Coagulation and Local Imentioning

confidence: 99%

Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome

Glas

Sluijs

Schultz

et al. 2013

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

To cite this article: Glas GJ, van der Sluijs KF, Schultz MJ, Hofstra J-JH, van der Poll T, Levi M. Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome. J Thromb Haemost 2013; 11: 17-25.Summary. Enhanced intrapulmonary fibrin deposition as a result of abnormal broncho-alveolar fibrin turnover is a hallmark of acute respiratory distress syndrome (ARDS), pneumonia and ventilator-induced lung injury (VILI), and is important to the pathogenesis of these conditions. The mechanisms that contribute to alveolar coagulopathy are localized tissue factor-mediated thrombin generation, impaired activity of natural coagulation inhibitors and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. There is an intense and bidirectional interaction between coagulation and inflammatory pathways in the bronchoalveolar compartment. Systemic or local administration of anticoagulant agents (including activated protein C, antithrombin and heparin) and profibrinolytic agents (such as plasminogen activators) attenuate pulmonary coagulopathy. Several preclinical studies show additional anti-inflammatory effects of these therapies in ARDS and pneumonia.

show abstract

“…TXA 2 is an arachidonic acid metabolite that is generated in several cell types and tissues, such as platelets, inflammatory cells, and pulmonary tissue, by the enzymes cyclooxygenase, hydroperoxidase, and tissue-specific isomerases (29,30). The binding of TXA 2 to the G protein-coupled thromboxane receptors (TPs) leads to a broad range of cellular responses, including integrin activation, platelet aggregation, contraction of smooth muscle cells, and increased vascular permeability, and can be involved in the development of ALI (31). Platelets express TPα, and endothelial cells express both TPα and TPβ (29).…”

Section: Introductionmentioning

confidence: 99%

Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation

Singbartl²,

2006

View full text Add to dashboard Cite

Acute lung injury (ALI) causes high mortality, but its molecular mechanisms are poorly understood. Acid aspiration is a frequent cause of ALI, leading to neutrophil sequestration, increased permeability, and deterioration of gas exchange. We investigated the role of platelet-neutrophil interactions in a murine model of acid-induced ALI. Acid aspiration induced P-selectin-dependent platelet-neutrophil interactions in blood and in lung capillaries. Reducing circulating platelets or blocking P-selectin halted the development of ALI. Bone marrow chimeras showed that platelet, not endothelial, P-selectin was responsible for the injury. The interaction of platelets with neutrophils and endothelia was associated with TXA 2 formation, with detrimental effects on permeability and tissue function. Activated platelets induced endothelial expression of ICAM-1 and increased neutrophil adhesion. Inhibition of platelet-neutrophil aggregation improved gas exchange, reduced neutrophil recruitment and permeability, and prolonged survival. The key findings were confirmed in a sepsis-induced model of ALI. These findings may translate into improved clinical treatments for ALI.

show abstract

Postinjury Thromboxane Receptor Blockade Ameliorates Acute Lung Injury

Cited by 32 publications

References 15 publications

Outcomes of Severe Sepsis and Septic Shock Patients on Chronic Antiplatelet Treatment: A Historical Cohort Study

Outcomes of Severe Sepsis and Septic Shock Patients on Chronic Antiplatelet Treatment: A Historical Cohort Study

Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome

Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation

Contact Info

Product

Resources

About