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.
- Reactive oxygen species
- Rewarming shock
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)