Role of superoxide ion formation in hypothermia/rewarming induced contractile dysfunction in cardiomyocytes

Niccole Schaible, Young Soo Han, Torkjel Tveita, Gary C Sieck

Research output: Contribution to journalArticle

Abstract

Rewarming following accidental hypothermia is associated with circulatory collapse due primarily to impaired cardiac contractile (systolic) function. Previously, we found that reduced myofilament Ca2+ sensitivity underlies hypothermia/rewarming (H/R)-induced cardiac contractile dysfunction. This reduced Ca2+ sensitivity is associated with troponin I (cTnI) phosphorylation. We hypothesize that H/R induces reactive oxygen species (ROS) formation in cardiomyocytes, which leads to cTnI phosphorylation and reduced myofilament Ca2+ sensitivity. To test this hypothesis, we exposed isolated rat cardiomyocytes to a 2-h period of severe hypothermia (15 °C) followed by rewarming (35 °C) with and without antioxidant (TEMPOL) treatment. Simultaneous measurements of cytosolic Ca2+ ([Ca2+]cyto) and contractile (sarcomere shortening) responses indicated that H/R-induced contractile dysfunction and reduced Ca2+ sensitivity was prevented in cardiomyocytes treated with TEMPOL. In addition, TEMPOL treatment blunted H/R-induced cTnI phosphorylation. These results support our overall hypothesis and suggest that H/R disrupts excitation-contraction coupling of the myocardium through a cascade of event triggered by excessive ROS formation during hypothermia. Antioxidant treatment may improve successful rescue of accidental hypothermia victims.

Original languageEnglish (US)
JournalCryobiology
DOIs
StateAccepted/In press - Jan 1 2018

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Hypothermia
Induced Hypothermia
Rewarming
hypothermia
Cardiac Myocytes
Superoxides
superoxide anion
Ions
ions
calcium
Phosphorylation
Myofibrils
phosphorylation
myofibrils
Reactive Oxygen Species
Antioxidants
reactive oxygen species
Excitation Contraction Coupling
Sarcomeres
Troponin I

Keywords

  • Antioxidant
  • Cardiomyocyte
  • Hypothermia
  • Reactive oxygen species
  • Rewarming
  • Rewarming shock
  • TEMPOL

ASJC Scopus subject areas

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

Cite this

Role of superoxide ion formation in hypothermia/rewarming induced contractile dysfunction in cardiomyocytes. / Schaible, Niccole; Han, Young Soo; Tveita, Torkjel; Sieck, Gary C.

In: Cryobiology, 01.01.2018.

Research output: Contribution to journalArticle

Schaible, Niccole ; Han, Young Soo ; Tveita, Torkjel ; Sieck, Gary C. / Role of superoxide ion formation in hypothermia/rewarming induced contractile dysfunction in cardiomyocytes. In: Cryobiology. 2018.
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