Role of circulating platelets and granulocytes in PAF-induced pulmonary dysfunction in awake sheep

Abstract

The effects of a single intravascular bolus injection of platelet-activating factor (PAF) on pulmonary hemodymics, lung mechanics, and lung fluid and solute exchange were studied in 13 chronically instrumented unanesthetized sheep. Since PAF has profound effects on both platelets and granulocytes, we investigated the effects of platelet and granulocyte depletion on the sheep''s response to exogenous PAF. Sheep received PAF when granulocyte and platelets counts were normal and after platelet depletion with rabbit antisheep platelet antibodies (n = 5) or granulocyte depletion with hydroxyurea (n = 5). Sheep served as their own controls, and the order of experimentation was varied. Bolus injections of PAF had reproducible effects on pulmonary hemodynamics (pulmonary arterial pressure increased acutely to 85 .+-. 3.7 cmH2O) and lung mechanics (dynamic compliance of the lungs decreased to 24.5 .+-. 3.8% of base line and resistance to airflow across the lungs increased > 10-fold) and caused marked increases in lung lymph concentrations of thromboxane B2 and 6-ketoprostaglandin F1.alpha.. The single bolus injection of PAF also caused marked prolonged elevations in lung lymph flow and increases in the lymph-to-plasma protein concentration ratio for 3 h after PAF. PAF had profound effects despite platelet and granulocyte depletion. Platelet depletion slightly attenuated the pulmonary hypertension observed after PAF injection. Platelet depletion also attenuated the increases in thromboxane B2 concentrations in lung lymph, and lung mechanics normalized more rapidly in platelet-depleted sheep. There were no statistically significant effects of granulocyte depletion to < 200 granulocytes/mm3 on any of the measured variables. We conclude that a single bolus injection of PAF causes profound abnormalities in pulmonary hemodyamics, lung mechanics, and lung fluid and solute exchange both in the presence and absence of circulating platelets or granulocytes.