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Levosimendan attenuates hypoxia-induced pulmonary hypertension in a porcine model.

Wiklund, Annaeva; Kylhammar, David LU and Rådegran, Göran LU (2012) In Journal of Cardiovascular Pharmacology 59(5). p.441-449
Abstract
BACKGROUND: Levosimendan was hypothesized to attenuate hypoxic pulmonary vasoconstriction (HPV). METHODS: 14 anaesthetized pigs (30,9±1,0kg) were studied in normoxia (FiO2∼0,21) and hypoxia (FiO2∼0,10), before and 10-90 min after infusion of placebo (n=7) or Levosimendan (n=7). RESULTS: Compared to normoxia, hypoxia-baseline at FiO2∼0,10 (n=14) increased PVR by 1.9±0.4 WU (p<0,001), MPAP by 14.3±0.9 mmHg (p<0,001), MRAP by 2.1±0.4 mmHg (p<0,001), PCWP by 1.5±0.3 mmHg (p<0,001), CO by 1.3±0.2 L·min (p<0,001) and HR by 19.9±5.5 beats·min (p<0,001). SVR decreased by 7,2±1.0 WU (p<0,001), MAP and SV remained unaltered (p=ns). Compared to hypoxia-baseline, Levosimendan decreased MPAP and PVR (p<0,05), by ∼9 and ∼19%,... (More)
BACKGROUND: Levosimendan was hypothesized to attenuate hypoxic pulmonary vasoconstriction (HPV). METHODS: 14 anaesthetized pigs (30,9±1,0kg) were studied in normoxia (FiO2∼0,21) and hypoxia (FiO2∼0,10), before and 10-90 min after infusion of placebo (n=7) or Levosimendan (n=7). RESULTS: Compared to normoxia, hypoxia-baseline at FiO2∼0,10 (n=14) increased PVR by 1.9±0.4 WU (p<0,001), MPAP by 14.3±0.9 mmHg (p<0,001), MRAP by 2.1±0.4 mmHg (p<0,001), PCWP by 1.5±0.3 mmHg (p<0,001), CO by 1.3±0.2 L·min (p<0,001) and HR by 19.9±5.5 beats·min (p<0,001). SVR decreased by 7,2±1.0 WU (p<0,001), MAP and SV remained unaltered (p=ns). Compared to hypoxia-baseline, Levosimendan decreased MPAP and PVR (p<0,05), by ∼9 and ∼19%, respectively, plateauing between 10-90 min. SV increased (p<0,05) by ∼22%, plateauing after 60 min. MRAP, PCWP, HR, CO, MAP, SVR and blood-O2-consumption remained unaltered (p=ns). Compared to hypoxia-baseline, with placebo, MPAP remained stable (p=ns), PVR increased (p<0,05) and CO decreased (p<0,05), by ∼20 and ∼11% after 60-90 and 30-90min, respectively. SV decreased (p<0,05) by ∼8%, plateauing after 60-90min. PCWP and MRAP decreased (p<0,05) by ∼12%, plateauing after 10-60 and 10-90min, respectively. MPAP, HR, MAP, SVR and blood-O2-consumption remained unchanged (p=ns), except at 60min where MAP decreased (p<0,05) by ∼4%. CONCLUSIONS: Levosimendan attenuated HPV and the cardio-depressive effect of sustained hypoxia. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cardiovascular Pharmacology
volume
59
issue
5
pages
441 - 449
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000303824900006
  • pmid:22240915
  • scopus:84861100274
ISSN
1533-4023
DOI
10.1097/FJC.0b013e31824938f0
language
English
LU publication?
yes
id
ab9cf00f-4e2c-4d2d-97e8-4195bf35fbd7 (old id 2336455)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22240915?dopt=Abstract
date added to LUP
2012-02-01 20:48:16
date last changed
2017-08-06 04:47:41
@article{ab9cf00f-4e2c-4d2d-97e8-4195bf35fbd7,
  abstract     = {BACKGROUND: Levosimendan was hypothesized to attenuate hypoxic pulmonary vasoconstriction (HPV). METHODS: 14 anaesthetized pigs (30,9±1,0kg) were studied in normoxia (FiO2∼0,21) and hypoxia (FiO2∼0,10), before and 10-90 min after infusion of placebo (n=7) or Levosimendan (n=7). RESULTS: Compared to normoxia, hypoxia-baseline at FiO2∼0,10 (n=14) increased PVR by 1.9±0.4 WU (p&lt;0,001), MPAP by 14.3±0.9 mmHg (p&lt;0,001), MRAP by 2.1±0.4 mmHg (p&lt;0,001), PCWP by 1.5±0.3 mmHg (p&lt;0,001), CO by 1.3±0.2 L·min (p&lt;0,001) and HR by 19.9±5.5 beats·min (p&lt;0,001). SVR decreased by 7,2±1.0 WU (p&lt;0,001), MAP and SV remained unaltered (p=ns). Compared to hypoxia-baseline, Levosimendan decreased MPAP and PVR (p&lt;0,05), by ∼9 and ∼19%, respectively, plateauing between 10-90 min. SV increased (p&lt;0,05) by ∼22%, plateauing after 60 min. MRAP, PCWP, HR, CO, MAP, SVR and blood-O2-consumption remained unaltered (p=ns). Compared to hypoxia-baseline, with placebo, MPAP remained stable (p=ns), PVR increased (p&lt;0,05) and CO decreased (p&lt;0,05), by ∼20 and ∼11% after 60-90 and 30-90min, respectively. SV decreased (p&lt;0,05) by ∼8%, plateauing after 60-90min. PCWP and MRAP decreased (p&lt;0,05) by ∼12%, plateauing after 10-60 and 10-90min, respectively. MPAP, HR, MAP, SVR and blood-O2-consumption remained unchanged (p=ns), except at 60min where MAP decreased (p&lt;0,05) by ∼4%. CONCLUSIONS: Levosimendan attenuated HPV and the cardio-depressive effect of sustained hypoxia.},
  author       = {Wiklund, Annaeva and Kylhammar, David and Rådegran, Göran},
  issn         = {1533-4023},
  language     = {eng},
  number       = {5},
  pages        = {441--449},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Cardiovascular Pharmacology},
  title        = {Levosimendan attenuates hypoxia-induced pulmonary hypertension in a porcine model.},
  url          = {http://dx.doi.org/10.1097/FJC.0b013e31824938f0},
  volume       = {59},
  year         = {2012},
}