title: Inotropic Effects of Prostacyclins on the Right Ventricle Are Abolished in Isolated Rat Hearts With Right-Ventricular Hypertrophy and Failure.
abstract: BACKGROUND
  Prostacyclin mimetics are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostanoids on right-ventricular (RV) function are unknown. We aimed to investigate the direct effects of prostacyclin mimetics on RV function in hearts with and without RV hypertrophy and failure.
  
  
  METHODS
  Wistar rats were subjected to pulmonary trunk banding to induce compensated RV hypertrophy (n = 32) or manifest RV failure (n = 32). Rats without banding served as healthy controls (n = 30). The hearts were excised and perfused in a Langendorff system and subjected to iloprost, treprostinil, epoprostenol, or MRE-269 in increasing concentrations. The effect on RV function was evaluated using a balloon-tipped catheter inserted into the right ventricle.
  
  
  RESULTS
  In control hearts, iloprost, treprostinil, and MRE-269 improved RV function. The effect was, however, absent in hearts with RV hypertrophy and failure. Treprostinil and MRE-269 even impaired RV function in hearts with manifest RV failure.
  
  
  CONCLUSIONS
  Iloprost, treprostinil, and MRE-269 improved RV function in the healthy rat heart. RV hypertrophy abolished the positive inotropic effect, and in the failing right ventricle, MRE-269 and treprostinil impaired RV function. This may be related to changes in prostanoid receptor expression and reduced coronary flow reserve in the hypertrophic and failing right ventricle.
authors.affiliation: *Department of Cardiology, Institute of Clinical Medicine, Aarhus University, Aarhus University Hospital, Aarhus, Denmark; †Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark; and ‡Institute of Cardiovascular Science, University College London, London, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Holmboe
authors.forename: Asger
authors.initials: A
authors.lastname: Andersen
authors.forename: Jacob
authors.initials: J
authors.lastname: Johnsen
authors.forename: Jan Møller
authors.initials: JM
authors.lastname: Nielsen
authors.forename: Rikke
authors.initials: R
authors.lastname: Nørregaard
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.forename: Lucie H
authors.initials: LH
authors.lastname: Clapp
authors.forename: Jens Erik
authors.initials: JE
authors.lastname: Nielsen-Kudsk
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009924:Organ Culture Techniques; D044062:Prostaglandins I / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D016278:Ventricular Function, Right / Q000187:drug effects* / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D044062:Prostaglandins I; D014665:Vasodilator Agents