Anesth Analg 2004;98:452-457
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000097167.39112.A3
CRITICAL CARE AND TRAUMA
Neutrophils and Neutrophil Products Do Not Mediate Pulmonary Hemodynamic Effects of Endotoxin on Oleic Acid-Induced Lung Injury
Laureen L. Hill, MD*,
Delphine L. Chen, MD ,
James Kozlowski, MS , and
Daniel P. Schuster, MD ,
Departments of *Anesthesia,
Radiology, and
Internal Medicine, Washington University School of Medicine, St. Louis, Missouri
Address correspondence and reprint requests to Daniel Schuster, MD, Pulmonary & Critical Care Division, Washington University School of Medicine, 510 S. Kingshighway, University Box 8225, St. Louis, MO 63110. Address e-mail to schusted{at}msnotes.wustl.edu
Small-dose endotoxin (Etx) prevents pulmonary perfusion redistribution away from edematous dorsal lung regions after oleic acid (OA)-induced injury in dogs, causing a significant deterioration in oxygenation. We hypothesized that small-dose Etx might mediate this effect via polymorphonuclear neutrophil (PMN) priming with release of inflammatory mediators such as platelet activating factor (PAF) or secretory phospholipase A2 (sPLA2). To test this hypothesis, we administered specific inhibitors directed against each mediator and used two strategies to generate neutropenia. PAF and sPLA2 inhibitors were administered before OA injury, followed 2 h later by small-dose Etx (n = 4 each group). PMN depletion was achieved by hydroxyurea administration for 5 days before the study to achieve absolute neutrophil counts <1000/mm3 (n = 4). Inhibition of PMN adherence to lung endothelium was achieved by the administration of an anti-CD18 monoclonal antibody immediately before lung injury (n = 5). Positron emission tomography was used to evaluate pulmonary perfusion distribution and lung water content. We observed no effect of these interventions on the perfusion pattern after Etx + OA. Thus, neither neutrophils nor PAF or sPLA2 mediate the effects of Etx on the pattern of perfusion in this model of lung injury.
IMPLICATIONS: Acute respiratory failure is characterized by severe decreases in blood oxygen. The pattern of blood flow within the lungs can contribute to this problem. This study investigated the potential role of white blood cells and their products in mediating abnormal pulmonary blood flow patterns in an experimental animal model of respiratory failure.
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T. Geiser
The Role of Neutrophils and Neutrophil Products in Pulmonary Hemodynamics of Endotoxin in Oleic Acid-Induced Lung Injury
Anesth. Analg.,
February 1, 2004;
98(2):
281 - 282.
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