Ann Thorac Surg 1996;61:1457
© 1996 The Society of Thoracic Surgeons
Discussion
Discussion
See also page 1453.
DR HARVEY I. PASS (Bethesda, MD): Thromboxane is one of the early pathways as far as lung injury is concerned. Can you comment on what affect this has on cytokine production and possibly free radicals?
Is there any golden period in which you can rescue animals if you give the blockade either as you start or after you start the injury? What other models would you use for endothelial injury to see whether the thromboxane blockade receptor is repeatable?
DR THIES: Thank you, Dr Pass. You address the very important point that these lungs were essentially pretreated with a thromboxane receptor antagonist. We have recently modified our protocol so as to double the study period and administer the thromboxane receptor antagonist after injury has been rendered. These ``rescued'' lungs also showed some improvement in oxygenation but to a lesser degree than pretreated lungs. These differences may be due in part to the kinetics of thromboxane to which you allude.
The active form of thromboxane is thromboxane A1, which has a half-life of only 30 seconds. By rendering a continuous injury over 20 minutes, we likely generated an uninterrupted stream of thromboxane A1. In pretreated lungs, this had little effect, as thromboxane receptors were occupied by our antagonist. In untreated lungs, however, this unopposed stream of vasoconstrictive thromboxane potentiated pulmonary hypertension and thereby diminished oxygenation. Lungs treated after injury or those ``rescued'' with the thromboxane receptor antagonist also demonstrated modest improvements in oxygenation. This seems to indicate that production of thromboxane A1 is ongoing, even after oleic acid infusion ceases.
This model lends itself to studying the effects of many other mediators of acute lung injury, including other eicosanoids and free radicals. As you indicated, the assay of these mediators and their by-products can be rather difficult. Another model that may clarify the effects of thromboxane receptor antagonism on injured endothelium is the study of isolated segments of injured pulmonary artery.
Related Article
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Thromboxane Receptor Blockade Improves Oxygenation in an Experimental Model of Acute Lung Injury
- Steven D. Thies, R. Scott Corbin, Charles D. Goff, Oliver A. R. Binns, Scott A. Buchanan, Kimberly S. Shockey, Henry F. Frierson, Jr, Jeffrey S. Young, Curtis G. Tribble, and Irving L. Kron
Ann. Thorac. Surg. 1996 61: 1453-1457.
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[Full Text]
