Cardiovascular effects of levosimendan during rewarming from hypothermia in rat

Erik Sveberg Dietrichs, Brage Håheim, Timofei Kondratiev, Gary C Sieck, Torkjel Tveita

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background: Previous research aimed at ameliorating hypothermia-induced cardiac dysfunction has shown that inotropic drugs, that stimulate the cAMP, - PKA pathway via the sarcolemmal β-receptor, have a decreased inotropic effect during hypothermia. We therefore wanted to test whether levosimendan, a calcium sensitizer and dose-dependent phosphodiesterase 3 (PDE3) inhibitor, is able to elevate stroke volume during rewarming from experimental hypothermia. Methods: A rat model designed for circulatory studies during experimental hypothermia (4. h at 15. °C) and rewarming was used. The following three groups were included: (1) A normothermic group receiving levosimendan, (2) a hypothermic group receiving levosimendan the last hour of stable hypothermia and during rewarming, and (3) a hypothermic placebo control group. Hemodynamic variables were monitored using a Millar conductance catheter in the left ventricle (LV), and a pressure transducer connected to the left femoral artery. In order to investigate the level of PKA stimulation by PDE3 inhibition, myocardial Ser23/24-cTnI phosphorylation was measured using Western-blot. Results: After rewarming, stroke volume (SV), cardiac output (CO) and preload recruitable stroke work (PRSW) were restored to within pre-hypothermic values in the levosimendan-treated animals. Compared to the placebo group after rewarming, SV, CO, PRSW, as well as levels of Ser23/24-cTnI phosphorylation, were significantly higher in the levosimendan-treated animals. Conclusion: The present data shows that levosimendan ameliorates hypothermia-induced systolic dysfunction by elevating SV during rewarming from 15. °C. Inotropic treatment during rewarming from hypothermia in the present rat model is therefore better achieved through calcium sensitizing and PDE3 inhibition, than β-receptor stimulation.

Original languageEnglish (US)
Pages (from-to)402-410
Number of pages9
JournalCryobiology
Volume69
Issue number3
DOIs
StatePublished - 2014

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Keywords

  • Accidental hypothermia
  • Calcium sensitizer
  • Cardiovascular support
  • Hypothermia
  • Levosimendan
  • PDE3 inhibitor
  • Rewarming
  • Rewarming shock
  • Troponin I
  • Troponin phosphorylation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Dietrichs, E. S., Håheim, B., Kondratiev, T., Sieck, G. C., & Tveita, T. (2014). Cardiovascular effects of levosimendan during rewarming from hypothermia in rat. Cryobiology, 69(3), 402-410. https://doi.org/10.1016/j.cryobiol.2014.09.007