Circulatory effects of PAF-acether in newborn piglets.
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.
Bradley
L M
LM
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Goldstein
R E
RE
Feuerstein
G
G
Czaja
J F
JF
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006439:Hemodynamics / Q000187:drug effects*; D006834:Hydrazines / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance
D000098:Acetophenones; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D010972:Platelet Activating Factor; D013777:Tetrazoles; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C044660:LY 171883; C045749:SQ 29548; D007213:Indomethacin