Effects of repetitive bolus injections of zymosan-activated plasma on lung mechanics and airway responsiveness in awake sheep.

We studied the pulmonary effects of repetitive bolus injections of autologous zymosan-activated plasma (ZAP) in nine chronically instrumented awake sheep. Aerosol histamine responsiveness was determined 1 h before and 4.5 h after the first bolus injection of ZAP. Each sheep received in the pulmonary artery a total of eight 5-ml bolus injections of ZAP separated by 30 min. On a separate day, with the order of experimentation varied to avoid sequential bias, six of the nine sheep also received "control" plasma (plasma prepared in the identical fashion as ZAP but not incubated with zymosan). "Control" plasma caused reproducible transient increases in pulmonary artery pressure, but it did not cause alterations in any of the other measured variables. Repetitive bolus injections of ZAP caused reproducible alterations in lung mechanics, pulmonary hemodynamics, lung fluid and solute exchange, oxygenation, and peripheral leukocyte counts. The increases in thromboxane-B2 concentrations in lung lymph and plasma were greatest after the first bolus injection of ZAP, with the magnitude of these changes diminishing on succeeding injections of ZAP. Aerosol histamine responsiveness did not increase after the eight bolus injections of ZAP.