title: Pulmonary hypertension in lambs with congenital diaphragmatic hernia: vasodilator prostaglandins, isoprenaline, and tolazoline.
abstract: After antenatal induction of diaphragmatic hernias in fetal lambs, prostaglandins D2, E1, and I2 were compared to tolazoline, or isoprenaline, for the treatment of pulmonary hypertension. When rendered hypoxic, these, and normal lambs, showed an increase in pulmonary artery pressure, a decrease in systemic pressure, and a decrease in pulmonary blood flow. All of the drugs altered that response, but to different degrees. None of the drugs tested was consistently successful in reversing the adverse affects of hypoxia, but prostaglandin D2 came closest to the ideal vasodilator, decreasing the pulmonary artery pressure in all seven hypoxic lambs having a diaphragmatic hernia. There was a concomitant increase in pulmonary blood flow in six; in the remaining lamb the decrease in blood flow induced by the hypoxia was arrested. At the same time, there was an increase in systemic artery pressure in three, the decrease was arrested in two, but the decrease continued in the other two. Isoprenaline was a more effective drug than tolazoline, producing an increase in pulmonary blood flow in five of the seven lambs, with minor decreases in systemic pressure in five. Tolazoline improved blood flow in three of six lambs (not all lambs survived the full study), with a marked decrease in systemic pressure in four of them. Prostaglandin D2 seems to be a useful drug for the treatment of patients having diaphragmatic hernias and pulmonary hypertension, and warrants further study. Isoprenaline was the most effective of the readily available drugs tested in this animal model.
authors.affiliation: Department of Paediatric Surgery, Adelaide Children's Hospital, Australia.
authors.forename: W D
authors.initials: WD
authors.lastname: Ford
authors.forename: S
authors.initials: S
authors.lastname: Sen
authors.forename: A P
authors.initials: AP
authors.lastname: Barker
authors.forename: C M
authors.initials: CM
authors.lastname: Lee
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D004195:Disease Models, Animal; D006548:Hernia, Diaphragmatic / Q000503:physiopathology; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D007545:Isoproterenol / Q000627:therapeutic use*; D015230:Prostaglandin D2 / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000503:physiopathology; D012756:Sheep; D014043:Tolazoline / Q000627:therapeutic use*
chemical_list: D014043:Tolazoline; D007545:Isoproterenol; D015230:Prostaglandin D2