Effect of phorbol myristate acetate-induced lung injury on airway blood flow

Abstract

The effects of phorbol myristate acetate (PMA) induced lung injury on the pulmonary and systemic blood flow contributions to the trachea and main bronchi (upper airways) were assessed in anesthetized dogs by injecting 15 microns radiolabeled microspheres into the right and left heart, respectively. Upper airway blood flow was studied in lungs given the following treatments: (1) PMA; (2) PMA in lungs pretreated with the thromboxane synthetase inhibitor OKY-046, and (3) PMA in lungs pretreated with the antioxidant catalase. After microsphere injections, the tracheal cartilage, tracheal muscle-mucosa, and main bronchi were excised. The results of this study indicate that under normal conditions, tracheal mucosa [33-52 ml.min-1.(100 g)-1] and tracheal cartilage [18-27 ml.min-1.(100 g)-1] blood flow is primarily systemic while both the systemic [12-18 ml.min-1.(100 g)-1] and pulmonary [6-12 ml.min-1.(100 g)-1] circulations contribute substantial amounts of blood flow to the main bronchi. PMA significantly decreased the systemic blood flow contribution to the tracheal cartilage and muscle-mucosa, and both the systemic and pulmonary blood flow contributions to the main bronchi to less than 50% of control values, an effect that was inhibited by catalase, but not by OKY-046. These results suggest that the effect of PMA-induced lung injury on the pulmonary and systemic blood flow contributions to the upper airways is at least partially mediated by oxygen radical production, probably hydrogen peroxide (H2O2), but not by the production of the arachidonic acid metabolite thromboxane.