Platelet-activating factor in porcine Pseudomonas acute lung injury.
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)
Byrne
K
K
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Sessler
C N
CN
Carey
P D
PD
Sielaff
T D
TD
Vasquez
A
A
Tatum
J L
JL
Hirsch
J I
JI
Sugerman
H J
HJ
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008171:Lung Diseases / Q000503:physiopathology*; D010972:Platelet Activating Factor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D011552:Pseudomonas Infections / Q000503:physiopathology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011804:Quinolines / Q000494:pharmacology; D013552:Swine
D010972:Platelet Activating Factor; D011804:Quinolines; C053130:SRI 63-675