The lung injury due to phorbol myristrate (PMA) mimic the adult respiratory distress syndrome and has been proposed to occur as the result of the activation of neutrophils and their adherence to endothelial cells. Once adhered the neutrophils are able to release oxidants and proteases that injure the pulmonary endothelium. The current literature supports the idea that neutrophil adherence is greatest at low blood flow rates and low shear stress levels. If this is the case, at higher blood flow rates and increased shear stress levels there should be a reduction in the adherence of neutrophils to endothelial cells in the isolated blood perfused canine lung lobe stimulated with PMA and therefore less injury. Isoproterenol (ISO) a beta-adrenergic agonist, has been found to be protective against some forms of lung injury. How blood flow rate affects the injury to PMA, neutrophil adherence and ISO's ability to protect against PMA-induced injury will be studied in the isolated blood perfused canine left lower lung lobe, perfused at low, 600 L/min or high flow, 2.0 L/min. The capillary filtration coefficient (Kf) will be used to access permeability. Endothelial ectoenzyme activity will be assessed from the single pass hydrolysis of 3H-benzoyl-Phe-Ala-Pro (BPAP, a synthetic substrate for ACE, angiotensin converting enzyme). Neutrophil adherence will be measures by isolating, radiolabeling and injecting 51Cr labeled neutrophils and obtaining tissue radioactive counts using a gamma counter. How blood floe rate may alter responses to injurious as well as protective agents in the lung is of importance and should be examined.
