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 x 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 less than 0.05 vs C), a significant (P less than 0.05 vs C) decrease in arterial
oxygen tension (PaO2) from 60 min, a significant (P less than 0.05 vs C) increase in extravascular lung water (EVLW) from 120 min, and a significant (P less than 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 less than 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 PaO2, 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.(ABSTRACT TRUNCATED AT 250 WORDS)