title: Roles of inflammation and apoptosis in experimental brain death-induced right ventricular failure.
abstract: Right ventricular (RV) dysfunction remains the leading cause of early death after cardiac transplantation. Methylprednisolone is used to improve graft quality; however, evidence for that remains empirical. We sought to determine whether methylprednisolone, acting on inflammation and apoptosis, might prevent brain death-induced RV dysfunction.
  
  
  
  After randomization to placebo (n = 11) or to methylprednisolone (n = 8; 15 mg/kg), 19 pigs were assigned to a brain-death procedure. The animals underwent hemodynamic evaluation at 1 and 5 hours after Cushing reflex (i.e., hypertension and bradycardia). The animals euthanized, and myocardial tissue was sampled. This was repeated in a control group (n = 8).
  
  
  
  At 5 hours after the Cushing reflex, brain death resulted in increased pulmonary artery pressure (27 ± 2 vs 18 ± 1 mm Hg) and in a 30% decreased ratio of end-systolic to pulmonary arterial elastances (Ees/Ea). Cardiac output and right atrial pressure did not change. This was prevented by methylprednisolone. Brain death-induced RV dysfunction was associated with increased RV expression of heme oxygenase-1, interleukin (IL)-6, IL-10, IL-1β, tumor necrosis factor (TNF)-α, IL-1 receptor-like (ST)-2, signal transducer and activator of transcription-3, intercellular adhesion molecules-1 and -2, vascular cell adhesion molecule-1, and neutrophil infiltration, whereas IL-33 expression decreased. RV apoptosis was confirmed by terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling staining. Methylprednisolone pre-treatment prevented RV-arterial uncoupling and decreased RV expression of TNF-α, IL-1 receptor-like-2, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and neutrophil infiltration. RV Ees/Ea was inversely correlated to RV TNF-α and IL-6 expression.
  
  
  
  Brain death-induced RV dysfunction is associated with RV activation of inflammation and apoptosis and is partly limited by methylprednisolone.
authors.affiliation: Department of Cardio-Vascular, Thoracic Surgery and Lung Transplantation, Centre Hospitalier Universitaire (CHU) Université Catholique de Louvain (UCL) Namur, Yvoir, Belgium; Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: asmae.belhaj@uclouvain.be.
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.
authors.forename: Laurence
authors.initials: L
authors.lastname: Dewachter
authors.affiliation: Department of Anatomopathology, Erasmus Academic Hospital, Brussels, Belgium; DIAPATH-Center for Microscopy and Molecular Imaging (CMMI), Gosselies, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Rorive
authors.affiliation: Department of Anatomopathology, Erasmus Academic Hospital, Brussels, Belgium.
authors.forename: Myriam
authors.initials: M
authors.lastname: Remmelink
authors.affiliation: Department of Anatomopathology, Universitaire Ziekenhuizen (UZ) Leuven, Katholiek Universiteit Leuven, Brussels, Belgium.
authors.forename: Birgit
authors.initials: B
authors.lastname: Weynand
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium; Department of Emergency, Erasmus Academic Hospital, Brussels, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Melot
authors.affiliation: Medical Laboratory, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Galanti
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Emeline
authors.initials: E
authors.lastname: Hupkens
authors.affiliation: Department of Cardio-Vascular, Thoracic Surgery and Lung Transplantation, Centre Hospitalier Universitaire (CHU) Université Catholique de Louvain (UCL) Namur, Yvoir, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sprockeels
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: Department of Intensive Care, Erasmus Academic Hospital, Brussels, Belgium.
authors.forename: Jacques
authors.initials: J
authors.lastname: Creteur
authors.affiliation: Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: McEntee
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: Department of Cardio-Vascular, Thoracic Surgery and Lung Transplantation, Centre Hospitalier Universitaire (CHU) Université Catholique de Louvain (UCL) Namur, Yvoir, Belgium; Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Benoît
authors.initials: B
authors.lastname: Rondelet
mesh_terms: D000818:Animals; D017209:Apoptosis; D001926:Brain Death; D006976:Hypertension, Pulmonary; D007249:Inflammation; D015850:Interleukin-6; D013552:Swine; D018497:Ventricular Dysfunction, Right
chemical_list: D015850:Interleukin-6
keywords: Cushing reflex; apoptosis; brain death; inflammation; methylprednisolone; right ventricular dysfunction