title: Levosimendan Prevents Pressure-Overload-induced Right Ventricular Failure.
abstract: BACKGROUND
  We investigated if chronic levosimendan treatment can prevent and revert pressure-overload-induced right ventricular hypertrophy and failure in rats.
  
  
  METHODS
  Right ventricular hypertrophy and failure was induced in Wistar rats by pulmonary trunk banding (PTB). The PTB rats were treated with levosimendan (3 mg·kg·d) 3 days before surgery [n = 10, prevention (PREV)], 3 weeks after surgery [n = 10, reversal (REV)] or vehicle (n = 10, VEH). Sham-operated rats received vehicle (n = 16, SHAM). Right ventricular function was evaluated 7 weeks after surgery by echocardiography, magnetic resonance imaging, pressure-volume relations, gross anatomy, and histology.
  
  
  RESULTS
  PTB induced right ventricular hypertrophy and compensated heart failure evident by reduced cardiac index (CI) without extra cardiac signs of heart failure. Levosimendan treatment prevented deterioration of right ventricular function measured by CI and right ventricular ejection fraction (RVEF) (CI: VEH vs. PREV 281 ± 17 vs. 362 ± 34 mL·min·kg, P ≤ 0.05, RVEF: VEH vs. PREV 57 ± 2% vs. 68 ± 3%, P ≤ 0.01) to values similar to SHAM (CI: 345 ± 21 mL·min·kg, RVEF: 71 ± 2%). RV contractility was improved in the REV group measured by preload recruitable stroke work (VEH vs. REV 39 ± 3 vs. 66 ± 10 mmHg P ≤ 0.05).
  
  
  CONCLUSIONS
  Chronic treatment with levosimendan prevents the development of right ventricular failure and improves contractility in established pressure-overload-induced right ventricular failure.
authors.affiliation: *Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus N, Denmark; and †MR Research Centre, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus N, Denmark.
authors.forename: Thomas Krarup
authors.initials: TK
authors.lastname: Hillgaard
authors.forename: Asger
authors.initials: A
authors.lastname: Andersen
authors.forename: Stine
authors.initials: S
authors.lastname: Andersen
authors.forename: Mads D
authors.initials: MD
authors.lastname: Vildbrad
authors.forename: Steffen
authors.initials: S
authors.lastname: Ringgaard
authors.forename: Jan M
authors.initials: JM
authors.lastname: Nielsen
authors.forename: Jens E
authors.initials: JE
authors.lastname: Nielsen-Kudsk
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004452:Echocardiography; D006333:Heart Failure / Q000188:drug therapy / Q000517:prevention & control*; D006835:Hydrazones / Q000008:administration & dosage / Q000494:pharmacology*; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy; D008279:Magnetic Resonance Imaging; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077464:Simendan; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy / Q000517:prevention & control*; D016278:Ventricular Function, Right / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan