Platelet-activating factor in porcine Pseudomonas acute lung injury

Abstract

We investigated the role of platelet-activating factor (PAF) in acute septic lung injury by examining the effects of the selective PAF antagonist SRI 63-675 and by measuring PAF in lung tissue in the porcine model. Four groups of pigs (15–25 kg) were studied: saline control (C, n = 5); Pseudomonas (Ps, n = 9), given 5 × 10 8 CFU/ml at 0.3 ml/20 kg/min intravenously over 1 hr; SRI ( n = 3), given SRI 63-675 in a 40 mg/kg bolus; and SRI + Ps ( n = 5). Ps infusion produced a fulminant lung injury characterized by a threefold increase in pulmonary arterial pressure at 30 min and persistent pulmonary hypertension ( P < 0.05 vs C), a significant ( P < 0.05 vs C) decrease in arterial oxygen tension ( PaO 2) from 60 min, a significant ( P < 0.05 vs C) increase in extravascular lung water (EVLW) from 120 min, and a significant ( P < 0.05 vs C) increase in albumin flux determined scintigraphically as slope index at 150–180 min. Systemic arterial pressure and cardiac index (CI) decreased significantly ( P < 0.05) in the Ps group vs C at 60 and 180 min, respectively. Bolus injection of SRI 63-675 at the time of Ps infusion blocked the early pulmonary hypertension, attenuated the early and late fall in PaO 2, ameliorated the increase in EVLW, and prevented the late (150–180 min) increase in albumin flux. SRI 63-675 had minimal effects on Ps-induced hypotension or alterations in CI. The quantity of PAF bioactivity in lung tissue as determined by rabbit platelet serotonin release was significantly ( P < 0.05) greater in Ps-infused animals than in saline controls. Collectively these results suggest that PAF plays a major role in septic lung injury.