Ann Thorac Surg 2000;69:408
© 2000 The Society of Thoracic Surgeons
Invited Commentaries
Thomas M. Egan, MDa
a Division of Cardiothoracic Surgery, University of North Carolina at Chapel Hill, 108 Burnett-Womack Building, CB #7065, Chapel Hill, NC 27599-7065, USA
Invited commentary
This study by Tanita and coworkers adds to a growing body of literature implicating activation of polymorphonuclear leukocytes (PMNs) as a contributing factor to pulmonary dysfunction. Using an isolated perfused rat lung model, the authors have investigated the impact of perfusion with human PMNs mechanically stimulated by gentle agitation in a glass vial. This resulted in increased CD18 integrin expression, assessed by immunofluorescence. The authors attempted to quantify capillary leak by modifying a method originally described by Aubrey Taylor’s group at the University of South Alabama. Capillary filtration coefficient has been used to quantify capillary leak in isolated perfused lung models for many years. It is based on the assumption that fluid leak into the lung interstitium is related to changes in intravascular pressure at the capillary level and the integrity of the endothelial membrane. In the classic model described by Taylor, isolated lung blocks are perfused while suspended from a force transducer until a steady state (constant weight) is achieved. Elevation of the venous reservoir results in increasing "back pressure" in the capillary circulation. Because the entire hydrostatic column may not be transmitted directly to the capillary bed (due to venous resistance), a double occlusion technique is generally used to quantify the increase in capillary pressure. In extensive studies in a variety of animals, Taylor’s group has demonstrated the reliability and reproducibility of the model.
In the current study, Tanita and colleagues modified the model by elevating both the arterial and venous reservoirs and by using a constant pressure (not constant flow) system. Since both the arterial and venous reservoirs are elevated the same amount, it is not clear why there should be any increase in net capillary pressure. The authors did demonstrate significant differences in weight gain in lungs reperfused with stimulated neutrophils. They were able to abrogate the weight change by using monoclonal antibodies to the CD-18 complex to block the impact of CD-18 upregulation. They also demonstrated a benefit of superoxide dismutase. The authors’ model does appear to demonstrate changes in degree of capillary leak, but caution should be exercised in comparing this study with others because of the altered methodology. A weakness of the model described by Taylor is that moderate elevations of pulmonary venous pressure can lead to alveolar flooding in cases of severe capillary dysfunction. The modifications put forward by the authors may be useful to allow studies of moderate to severe capillary leak. However, the authors should have chosen a different name for their measure of capillary leak to provide consistency among different investigators using similar (but not identical) models. Standardizing methods is a useful way to allow investigators to compare their results and the impact of a variety of maneuvers. Standardizing nomenclature is equally important.
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Superoxide possibly produced in endothelial cells mediates the neutrophil-induced lung injury
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Ann. Thorac. Surg. 2000 69: 402-407.
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