title: Effects of levosimendan on acute pulmonary embolism-induced right ventricular failure.
abstract: OBJECTIVE
  Repeated episodes of pulmonary embolism can persistently increase pulmonary arterial pressure and depress right ventricular contractility. We investigated the effects of levosimendan on right ventricular-pulmonary arterial coupling in this model of right ventricular failure.
  
  
  METHODS
  Prospective, controlled, randomized animal study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Fourteen anesthetized piglets.
  
  
  METHODS
  Repeated acute pulmonary embolisms were induced with autologous blood clots to induce persistent right ventricular failure. Animals were randomly assigned to a control or levosimendan group. Levosimendan 20 microg/kg was administered in 10 mins followed by 0.2 microg/kg/min or same volumes of isotonic saline.
  
  
  RESULTS
  Pulmonary artery distal resistance and proximal elastance by pressure-flow relationships and vascular impedance were measured. We noted right ventricle contractility by the end-systolic pressure-volume relationship (Ees), pulmonary artery effective elastance by the end-diastolic to end-systolic relationship (Ea), and right ventricular-pulmonary arterial coupling efficiency by the Ees/Ea ratio. The gradual pulmonary artery embolism increased pulmonary artery resistance and elastance, increased Ea from 1.01 +/- 0.17 to 5.58 +/- 0.37 mm Hg/mL, decreased Ees from 1.75 +/- 0.12 to 1.29 +/- 0.20 mm Hg/mL, and decreased Ees/Ea from 1.74 +/- 0.20 to 0.24 +/- 0.09. Compared with placebo, levosimendan decreased pulmonary arterial elastance and characteristic impedance. Right ventricular-pulmonary arterial coupling was restored by both an increase in right ventricular contractility and a decrease in right ventricular afterload.
  
  
  CONCLUSIONS
  A gradual increase in pulmonary artery pressure induced by pulmonary embolism persistently worsens pulmonary artery hemodynamics, right ventricular contractility, right ventricular-pulmonary arterial coupling, and cardiac output. Levosimendan restores right ventricular-pulmonary arterial coupling better than placebo, because of combined pulmonary vasodilation and increased right ventricular contractility.
authors.affiliation: Laboratory of Hemodynamics and Cardiovascular Mechanisms and the LERTIM, Faculty of Medicine, Marseille, France. fkerbaul@yahoo.fr
authors.forename: François
authors.initials: F
authors.lastname: Kerbaul
authors.forename: Vlad
authors.initials: V
authors.lastname: Gariboldi
authors.forename: Roch
authors.initials: R
authors.lastname: Giorgi
authors.forename: Choukri
authors.initials: C
authors.lastname: Mekkaoui
authors.forename: Régis
authors.initials: R
authors.lastname: Guieu
authors.forename: Pierre
authors.initials: P
authors.lastname: Fesler
authors.forename: François
authors.initials: F
authors.lastname: Gouin
authors.forename: Serge
authors.initials: S
authors.lastname: Brimioulle
authors.forename: Frédéric
authors.initials: F
authors.lastname: Collart
mesh_terms: D000208:Acute Disease; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006835:Hydrazones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000209:etiology; D011652:Pulmonary Circulation / Q000187:drug effects; D011655:Pulmonary Embolism / Q000150:complications*; D011724:Pyridazines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D012119:Respiration / Q000187:drug effects; D000077464:Simendan; D013552:Swine; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy* / Q000209:etiology
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan