AJP - Heart and Circulatory Physiology, Vol 256, Issue 1 205-H212, Copyright © 1989 by American Physiological Society
Circulatory effects of PAF-acether in newborn piglets
L. M. Bradley, R. E. Goldstein, G. Feuerstein and J. F. Czaja
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Platelet-activating factor (PAF-acether) is a lipid mediator that can
exhibit potent vasoconstrictor influence in the pulmonary vessels.
Therefore, the release of PAF-acether during inflammatory conditions in
newborns might cause deleterious increases in pulmonary vascular tone.
Thirty-four anesthetized open-chest newborn piglets were given 0.01-1 nmol
PAF-acether iv. In separate experiments, animals were untreated or treated
with either indomethacin (a cyclooxygenase inhibitor), SQ 29548 (a
thromboxane receptor blocker), or LY 171883 (a leukotriene receptor
blocker). The primary hemodynamic change was a 67 to 1,537% increase in the
pulmonary vascular resistance index (PVRI) (P less than 0.01): mean
pulmonary artery pressure (PAP) rose significantly at all doses tested,
whereas only the largest dose consistently decreased cardiac index.
Treatment with indomethacin or SQ 29548 prevented the decrease in cardiac
index and attenuated the PAF-acether-induced rises in PAP and PVRI. Vehicle
and LY 171883 had no effect. The inhibitory influence of indomethacin and
SQ 29548 suggests that an important component of PAF-acether's pulmonary
vasoconstrictor action is mediated (at least in the newborn piglet) by
cyclooxygenase products, most likely thromboxane.
