Platelet-activating factor and bacteremia-induced pulmonary hypertension
L C Clavijo1, M B Carter, P J Matheson
1Department of Surgery, University of Louisville, Louisville, Kentucky 40206, USA.
The Journal of Surgical Research
|January 25, 2000
Summary
Platelet-activating factor (PAF) drives pulmonary hypertension during E. coli sepsis, involving endothelin-1 and neutrophil activation. PAF also causes lung injury, but hypoxemia develops later.
Area of Science:
- Pulmonary Medicine
- Sepsis Pathophysiology
- Vascular Biology
Background:
- Acute lung injury is a common complication of gram-negative sepsis, characterized by pulmonary hypertension and increased lung vascular permeability.
- Platelet-activating factor (PAF) is a key mediator in bacterial sepsis, influencing both pulmonary hypertension and edema.
- This study investigates the mechanism by which E. coli bacteremia induces pulmonary injury and the role of PAF.
Purpose of the Study:
- To elucidate the mechanism of PAF-induced pulmonary hypertension during E. coli bacteremia.
- To determine the role of endothelin-1 (ET) and nitric oxide (NO) in PAF-mediated pulmonary injury.
- To assess the contribution of neutrophil activation and sequestration to sepsis-induced lung injury.
Main Methods:
- Adult male Sprague-Dawley rats were subjected to E. coli bacteremia or sham sepsis.
- Hemodynamic parameters (PAP, BP, HR) and arterial blood gases were monitored.
- PAF receptor antagonist (WEB 2086) was administered to assess its inhibitory effects.
- Serum ET and nitric oxide metabolites (NOx) were measured, along with lung myeloperoxidase (MPO) activity and histology.
Main Results:
- E. coli bacteremia rapidly increased heart rate, pulmonary artery pressure, and respiratory rate within 20 minutes.
- Pretreatment with WEB 2086 completely prevented these hemodynamic changes.
- PAF-dependent mechanisms increased serum ET, lung MPO activity, and neutrophil sequestration.
- Increased NO production appeared to be independent of PAF.
Conclusions:
- E. coli bacteremia induces rapid pulmonary hypertension mediated by PAF, endothelin-1, and neutrophil activation.
- PAF also contributes to microvascular injury and lung leak, but hypoxemia develops more slowly.
- Hypoxic vasoconstriction is unlikely to be a significant contributor to early pulmonary hypertension in this model.
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