Pulmonary effects of zymosan activated plasma and phorbol myristate acetate in anaesthetized and awake rabbits.

The ability of two polymorphonuclear granulocyte (PMN) activators, Zymosan activated plasma (ZAP) and Phorbol myristate acetate (PMA), to induce an adult respiratory distress syndrome (ARDS) type lung injury was compared in awake and anaesthetized rabbits. The preparatory procedure itself decreased the concentrations of circulating PMN and lymphocytes in anaesthetized animals. ZAP acutely lowered the number of circulating leukocytes due to a fall in PMN only, this was followed by a rebound. Both effects were more marked in awake than in anaesthetized animals. PMA caused a virtual disappearance of both PMN and lymphocytes from the blood. There was no rebound, and no difference between anaesthetized and awake animals. The activators caused equal increases in pulmonary arterial pressure (about 0.67 kPa) initially. This was followed by a return to baseline in ZAP animals, but a further increase in those given PMA. Increased airway pressure (0.4 kPa) was seen only in the PMA group; PaO2 decreased only in awake rabbits given PMA. Both activators, as well as the preparatory procedure itself, caused PMN accumulations in the alveolar septa, septal thickening, and modest perivascular edema with intact tissue architecture. PMA caused the most marked changes. Wet/dry lung weight ratios were only moderately increased. In conclusion, ZAP and PMA had different effects on circulating leukocytes, but gave nearly the same degree of PMN accumulation in the lungs. The modest edema indicated some increased microvascular leakage, but a fully developed ARDS-type lung injury did not occur.