Sustained Effects of Platelet-Activating Factor Infusion in Piglets

Abstract

Acute exposure to platelet-activating factor (PAF) causes severe pulmonary vasoconstriction (PV), but its action may be markedly limited by tachyphylaxis. To determine the effects of PAF exposure per se and the effects compared with the hypoxemic state (33 +/- 1 mm Hg), PAF infusions (0.05-0.15 nmol/kg/min x 30-180 min) were administered to 15 open-chested, anesthetized, neonatal piglets before and during administration of selective receptor blockers to PAF (SRI 63,441, 5 mg/kg i.v. or WEB 2086, 10 mg/kg i.v.) or vehicle. Measurements included mean pulmonary (PAP) and systemic arterial pressures, cardiac index, right and left ventricular pressures and dimensions, and coronary blood flow. Mean PAP and pulmonary vascular resistance index rose in response to 30 min PAF infusion (14 +/- 1 to 30 +/- 1 mm Hg and 4500 +/- 700 to 16,400 +/- 1900 dynes s cm-5.kg, both p less than 0.01, n = 10). Similar changes occurred when PAF was infused for 180 min (n = 5). Other parameters were unaffected. Acute hypoxia also increased in PAP and pulmonary vascular resistance index (17 +/- 1 to 32 +/- 2 mm Hg and 6400 +/- 900 to 17,100 +/- 1800 dynes s cm-5.kg, both p less than 0.01) and did not alter other measured variables. Treatment with SRI 63,441 prevented PAF-induced increases in PAP (14 +/- 1 to 14 +/- 1 mm Hg, p less than 0.05) and pulmonary vascular resistance index (5300 +/- 900 to 5500 +/- 800 dynes s cm-5.kg, p less than 0.05) but failed to alter the response to hypoxia. SRI 63,441 and WEB 2086, administered during PAF infusion, rapidly reversed PAF action. Vehicle had no effect. We conclude that PAF can produce severe and sustained PV in vivo and that PAF receptor blockade may be useful in treatment of neonatal disease featuring PAF-mediated PV. PAF receptors may not be involved in PV induced by hypoxia.