title: Almitrine and doxapram in experimental lung injury.
abstract: Almitrine and doxapram, two structurally unrelated peripheral chemoreceptor agonists, have been shown to enhance hypoxic pulmonary vasoconstriction in anesthetized dogs. We hypothesized that these drugs would increase pulmonary vascular tone and improve gas exchange in canine lung injury caused by oleic acid (OA). Pulmonary hemodynamics and gas exchange were investigated in pentobarbital-anesthetized dogs before and after intravenously administered OA 0.09 ml/kg and again after placebo (n = 6), almitrine 2 micrograms/kg/min (n = 6), or doxapram 20 micrograms/kg/min (n = 6) in a randomized order. Cardiac output (Q) was manipulated using a femoral arteriovenous bypass and an inferior vena cava balloon catheter to construct mean pulmonary artery pressure (Ppa)-Q plots in order to discriminate active from passive changes in Ppa. Gas exchange was assessed by measuring arterial PO2 and intrapulmonary shunt, determined using a sulfur hexafluoride infusion. OA increased Ppa over the range of Q studied, and it deteriorated gas exchange by an increase in intrapulmonary shunt. After OA, placebo had no effect on Ppa, arterial PO2, or intrapulmonary shunt. Both almitrine and doxapram further increased Ppa at all levels of Q studied, but they did not affect indices of gas exchange after OA. We conclude that in this experimental model of acute lung injury, almitrine and doxapram induce pulmonary vasoconstriction without, however, diverting blood flow toward better oxygenated lung regions.
authors.affiliation: Laboratory of Cardiovascular and Respiratory Physiology, Erasme University Hospital, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Leeman
authors.forename: M
authors.initials: M
authors.lastname: Delcroix
authors.forename: J L
authors.initials: JL
authors.lastname: Vachiéry
authors.forename: C
authors.initials: C
authors.lastname: Mélot
authors.forename: R
authors.initials: R
authors.lastname: Naeije
mesh_terms: D015765:Almitrine / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D004285:Dogs; D004315:Doxapram / Q000009:adverse effects / Q000627:therapeutic use*; D019301:Oleic Acid; D009829:Oleic Acids; D011652:Pulmonary Circulation / Q000187:drug effects*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000188:drug therapy; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D009829:Oleic Acids; D019301:Oleic Acid; D004315:Doxapram; D015765:Almitrine