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Levosimendan Attenuates Hypoxia-Induced Pulmonary Hypertension in a Porcine Model

Wiklund, Annaeva MD*,†,‡; Kylhammar, David MD*,†,‡; Rådegran, Göran MD, MSc Eng Phys, Dr Med, Assoc Professor*,†,‡

Journal of Cardiovascular Pharmacology: May 2012 - Volume 59 - Issue 5 - p 441–449
doi: 10.1097/FJC.0b013e31824938f0
Original Article

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.

*The Öresund Cardiovascular Research Collaboration, The Clinic for Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden

Department of Cardiology, Institution for Clinical Sciences, Lund, Lund University, Lund, Sweden

The Copenhagen Muscle Research Centre, Rigshospitalet and the Panum Institute, University of Copenhagen, Copenhagen, Denmark.

Reprints: Annaeva Wiklund, MD, The Clinic for Heart Failure and Valvular Disease, EA15, Skåne University Hospital, Lund, Sweden (e-mail:

Supported by Maggie Stephens, Crafoord, Per Westling, Ebba and Herman Bings legat, Skåne University Hospital and ALF Foundations, as well as the Lund University Medical Faculty's Summer Research Scholarship, Lund, Sweden.

The authors report no conflicts of interest.

Received July 6, 2011

Accepted January 2, 2012

© 2012 Lippincott Williams & Wilkins, Inc.