title: Myocardial inflammation in experimental acute right ventricular failure: Effects of prostacyclin therapy.
abstract: BACKGROUND
  Acute transient pulmonary hypertension may induce a state of persistent right ventricular (RV) failure. We hypothesized that this could be related to an activation of inflammatory processes and reduced by prostacyclin therapy.
  
  
  METHODS
  Sixteen dogs were assigned to a 90-minute pulmonary artery banding (n = 8), or to a sham operation (n = 8). Hemodynamic variables were measured 30 minutes after banding release. This was repeated in 7 dogs with pulmonary artery banding-induced RV failure, followed by a 60-minute epoprostenol infusion. After euthanasia of the animals, myocardial tissue was sampled.
  
  
  RESULTS
  Persistent RV failure was associated with increased myocardial expression of interleukin (IL)-1β, IL-6, monocyte chemoattractant protein 1, pro-inflammatory IL-6/IL-10, and neutrophil and macrophage infiltration, whereas heme oxygenase 1 expression was decreased. These changes were observed in RV and to a lesser extent in the left ventricle (LV). In the RV only, expressions of prostacyclin synthase and anti-inflammatory IL-10 and IL-33 decreased and vascular cell adhesion molecule expression increased, whereas macrophage inflammatory protein-1α and intercellular adhesion molecule 1 expressions remained unchanged. After epoprostenol infusion, there was decreased expression of IL-1β, macrophage inflammatory protein-1α, and vascular cell adhesion molecule 1 and increased IL-10 expression in the RV and the LV, whereas monocyte chemoattractant protein-1 decreased in the RV only. Epoprostenol infusion resulted in decreased RV IL-6/IL-10 and pro-apoptotic Bax/Bcl-2, together with decreased RV neutrophil and RV and LV macrophage infiltration. The RV ratio of end systolic-to-pulmonary arterial elastances was inversely correlated to RV IL-6/IL-10, macrophage, and neutrophil infiltration, and to RV heme oxygenase-1 and IL-33 expression.
  
  
  CONCLUSIONS
  Acute afterload-induced persistent RV failure is associated with an activation of inflammatory processes, which are limited by epoprostenol.
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Dewachter
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium; Department of Thoracic Surgery, Erasmus University Hospital, Brussels, Belgium; Department of Cardio-Vascular and Thoracic Surgery, Mont-Godinne University Hospital, Dinant, Belgium.
authors.forename: Asmae
authors.initials: A
authors.lastname: Belhaj
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium; Department of Thoracic Surgery, Erasmus University Hospital, Brussels, Belgium; Department of Cardio-Vascular and Thoracic Surgery, Mont-Godinne University Hospital, Dinant, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Rondelet
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Vercruyssen
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Schraufnagel
authors.affiliation: Department of Anatomopathology, Erasmus University Hospital, Brussels, Belgium.
authors.forename: Myriam
authors.initials: M
authors.lastname: Remmelink
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium; Department of Intensive Care, Erasmus University Hospital, Brussels, Belgium.
authors.forename: Serge
authors.initials: S
authors.lastname: Brimioulle
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium; Department of Cardiovascular Anesthesia and Intensive Care, La Timone University Hospital, Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Kerbaul
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Naeije
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: ldewacht@ulb.ac.be.
authors.forename: Laurence
authors.initials: L
authors.lastname: Dewachter
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D011464:Epoprostenol / Q000627:therapeutic use*; D009205:Myocarditis / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D015815:Cell Adhesion Molecules; D018925:Chemokines; D011464:Epoprostenol
keywords: Right ventricular failure; acute right heart syndrome; inflammation; prostacyclin; pulmonary hypertension; ventriculoarterial coupling