title: Search for an animal model to investigate selective pulmonary vasodilation.
abstract: Pulmonary arterial hypertension is a life-threatening disease with a poor prognosis. Oral treatment with vasodilators is often limited by systemic hypotension. Inhalation of vasodilators offers the opportunity for selective pulmonary vasodilation. Testing selective pulmonary vasodilation by inhaled nitric oxide or alternative substances in animal models requires an increased pulmonary vascular tone. The aim of this study was to identify animal models that are suitable for investigating selective pulmonary vasodilation. To do so, a haemodynamic stable pulmonary hypertension was initiated, with a 30 min duration deemed to be a sufficient time interval before and after a possible intervention. In anaesthetized and mechanically-ventilated Sprague-Dawley rats pulmonary hypertension was induced either by acute hypoxia due to reduction of the inspired oxygen fraction from 0.21 to 0.1 ( n = 6), a fixed infusion rate of the thromboxane analogue U46619 (240 ng/min; n = 6) or a monocrotaline injection (MCT; 60 mg/kg applied 23 days before the investigation; n = 7). The animals were instrumented to measure right ventricular and systemic arterial pressures. Acute hypoxia caused a short, and only transient, increase of pulmonary artery pressure as well as profound systemic hypotension which suggested haemodynamic instability. U46619 infusion induced variable changes in the pulmonary and systemic vascular tone without sufficient stabilization within 30 min. MCT provoked sustained pulmonary hypertension with normal systemic pressure values and inhalation of nitric oxide caused selective pulmonary vasodilation. In conclusion, out of the three examined rat animal models only MCT-induced pulmonary hypertension is a solid and reliable model for investigating selective pulmonary vasodilation.
authors.affiliation: 1 Department of Anaesthesia and Intensive Care Medicine, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors.forename: Bodil
authors.initials: B
authors.lastname: Petersen
authors.affiliation: 1 Department of Anaesthesia and Intensive Care Medicine, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Busch
authors.affiliation: 1 Department of Anaesthesia and Intensive Care Medicine, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Noreikat
authors.affiliation: 1 Department of Anaesthesia and Intensive Care Medicine, Medical Faculty, University of Leipzig, Leipzig, Germany.|2 Department of Anaesthesia, Intensive Care and Emergency Medicine, Bergmannstrost Hospital, Halle, Germany.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Homeister
authors.affiliation: 3 Division of Clinical Pharmacology, Rudolf-Boehm Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Regenthal
authors.affiliation: 1 Department of Anaesthesia and Intensive Care Medicine, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors.forename: Udo X
authors.initials: UX
authors.lastname: Kaisers
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008168:Lung; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D014665:Vasodilator Agents
keywords: U46619; acute hypoxia; monocrotaline; rat animal model; selective pulmonary vasodilation