title: Fetal pulmonary vasodilation after exogenous platelet-activating factor.
abstract: To determine the fetal pulmonary vascular response to platelet-activating factor (PAF), we studied the hemodynamic effects of the infusion of PAF directly into the left pulmonary artery in 21 chronically catheterized fetal lambs. Left pulmonary arterial blood flow (Q) was measured with electromagnetic flow transducers. Ten-minute infusions of low-dose PAF (10-100 ng/min) produced increases in Q from a baseline of 71 +/- 5 to 207 +/- 20 ml/min (P less than 0.001) without changes in pulmonary arterial pressure. Pulmonary vasodilation with PAF was further confirmed through increases in Q with brief (15-s) infusions and increases in the slope of the pressure-flow relationship as assessed by rapid incremental compressions of the ductus arteriosus during PAF infusion. Infusion of Lyso-PAF had no effect on Q or pulmonary arterial pressure. Treatment with CV-3988, a selective PAF receptor antagonist, but not with meclofenamate, atropine, or diphenhydramine and cimetidine blocked the response to PAF infusion and did not affect baseline tone. Systemic infusion of high-dose PAF (300 ng/min) through the fetal inferior vena cava increased pulmonary arterial pressure (46.5 +/- 1.0 to 54.8 +/- 1.9 mmHg, P less than 0.01) and aorta pressure (44.3 +/- 1.0 to 52.7 +/- 2.2 mmHg, P less than 0.01) while also increasing Q. Neither PAF nor CV-3988 changed the gradient between pulmonary arterial and aorta pressures, suggesting that PAF does not affect ductal tone. We conclude that PAF is a potent fetal pulmonary vasodilator and that the effects are not mediated through cyclooxygenase products or by cholinergic or histaminergic effects.
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver.
authors.forename: F J
authors.initials: FJ
authors.lastname: Accurso
authors.forename: S H
authors.initials: SH
authors.lastname: Abman
authors.forename: R B
authors.initials: RB
authors.lastname: Wilkening
authors.forename: G S
authors.initials: GS
authors.lastname: Worthen
authors.forename: P
authors.initials: P
authors.lastname: Henson
mesh_terms: D000818:Animals; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008469:Meclofenamic Acid / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D011247:Pregnancy; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D008469:Meclofenamic Acid; C037913:CV 3988