title: Levosimendan attenuates hypoxia-induced pulmonary hypertension in a porcine model.
abstract: BACKGROUND
  Levosimendan was hypothesized to attenuate hypoxic pulmonary vasoconstriction (HPV).
  
  
  METHODS
  Fourteen anaesthetized pigs (30.9 ± 1.0 kg) were studied in normoxia (FiO₂∼0.21) and hypoxia (FiO₂∼0.10), before and 10-90 minutes after infusion of placebo (n = 7) or levosimendan (n = 7).
  
  
  RESULTS
  Compared with normoxia, hypoxia baseline at FiO₂∼0.10 (n = 14) increased pulmonary vascular resistance (PVR) by 1.9 ± 0.4 Wood Units (WU) (P < 0.001), mean pulmonary artery pressure (MPAP) by 14.3 ± 0.9 mm Hg (P < 0.001), mean right atrial pressure (MRAP) by 2.1 ± 0.4 mm Hg (P < 0.001), pulmonary capillary wedge pressure (PCWP) by 1.5 ± 0.3 mm Hg (P < 0.001), cardiac output (CO) by 1.3 ± 0.2 L/minute (P < 0.001) and heart rate (HR) by 19.9 ± 5.5 beats·per minute (P < 0.001). Systemic vascular resistance (SVR) decreased by 7.2 ± 1.0 WU (P < 0.001), MAP and stroke volume (SV) remained unaltered (P = ns). Compared with hypoxia baseline, levosimendan decreased MPAP and PVR (P < 0.05), by approximately 9% and 19%, respectively, plateauing between 10 and 90 minutes. SV increased (P < 0.05) by approximately 22%, plateauing after 60 minutes. MRAP, PCWP, HR, CO, MAP, SVR, and blood-O₂ consumption remained unaltered (P = ns). Compared with hypoxia baseline, with placebo, MPAP remained stable (P = ns), PVR increased (P < 0.05) and CO decreased (P < 0.05) by approximately 20% and 11% after 60-90 and 30-90 minutes, respectively. SV decreased (P < 0.05) by approximately 8%, plateauing after 60-90 minutes. PCWP and MRAP decreased (P < 0.05) by approximately 12%, plateauing after 10-60 and 10-90 minutes, respectively. MPAP, HR, MAP, SVR, and blood-O₂ consumption remained unchanged (P = ns), except at 60 minutes where MAP decreased (P < 0.05) by approximately 4%.
  
  
  CONCLUSIONS
  Levosimendan attenuated HPV and the cardiodepressive effect of sustained hypoxia.
authors.affiliation: The Öresund Cardiovascular Research Collaboration, The Clinic for Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden. annaeva.wiklund@gmail.com
authors.forename: Annaeva
authors.initials: A
authors.lastname: Wiklund
authors.forename: David
authors.initials: D
authors.lastname: Kylhammar
authors.forename: Göran
authors.initials: G
authors.lastname: Rådegran
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications*; D010101:Oxygen Consumption / Q000187:drug effects; D011724:Pyridazines / Q000494:pharmacology*; D000077464:Simendan; D013552:Swine; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan