Piriprost: A Putative Leukotriene Synthesis Inhibitor Increases Pulmonary Blood Flow in Fetal Lambs

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Abstract
: Leukotrienes may control fetal pulmonary vascular tone since infusions of putative leukotriene receptor antagonists markedly increase pulmonary blood flow and decrease pulmonary vascular resistance in fetal lambs. This hypothesis would be strengthened if inhibition of leukotriene synthesis also produced similar hemodynamic changes. We therefore studied the effects of piriprost (U 60257), a putative leukotriene synthesis inhibitor, on thirteen fetal lambs at 137 to 140 days gestation. In preliminary studies in four fetal lambs, doses of U 60257 greater than 20 mg/kg increased pulmonary blood flow. In the nine other fetal lambs, U 60257 (31.7 ± 4.1 mg/kg) increased pulmonary blood flow by 502% (p < 0.05) and decreased pulmonary vascular resistance by 87% (p < 0.05). Pulmonary arterial and left atrial pressures were unchanged. Descending aortic pressure was increased (p < 0.05) and heart rate was decreased (p < 0.05). The abilities of both putative leukotriene synthesis inhibitors and leukotriene receptor antagonists to similarly increase fetal pulmonaryblood flow and decrease pulmonary vascular resistance are consistent with the hypothesis that leukotrienes play a role in regulating fetal pulmonary vascular tone.

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