title: Antiapoptotic cardioprotective effect of hypothermia treatment against oxidative stress injuries.
abstract: OBJECTIVE
  The effect of hypothermia on cardiomyocyte injury induced by oxidative stress remains unclear. The authors investigated the effects of hypothermia on apoptosis and mitochondrial dysfunction in cardiomyocytes exposed to oxidative stress.
  
  
  METHODS
  Cardiomyocytes (H9c2) derived from embryonic rat heart cell culture were exposed to either normothermic (37 degrees C) or hypothermic (31 degrees C) environments before undergoing oxidative stress via treatment with hydrogen peroxide (H(2)O(2)). The degree of apoptosis was determined by annexin V and terminal deoxynucleotidyl transferase (TUNEL) staining. The amount of reactive oxygen species (ROS) was compared after H(2)O(2) exposure between normo- and hypothermic-pretreated groups. Mitochondrial dysfunction in both groups was measured by differential reductase activity and transmembrane potential (DeltaPsim).
  
  
  RESULTS
  Hydrogen peroxide induced significant apoptosis in both normothermic and hypothermic cardiomyocytes. Hypothermia ameliorated apoptosis as demonstrated by decreased annexin V staining (33 +/- 1% vs. 49 +/- 4%; p < 0.05) and TUNEL staining (27 +/- 17% vs. 80 +/-25%; p < 0.01). The amount of intracellular ROS increased after H(2)O(2) treatment and was higher in the hypothermic group than that in the normothermic group (237.9 +/- 31.0% vs. 146.6 +/- 20.6%; p < 0.05). In the hypothermic group, compared with the normothermic group, after H(2)O(2) treatment mitochondrial reductase activity was greater (72.0 +/- 17.9% vs. 27.0 +/- 13.3%; p < 0.01) and the mitochondria DeltaPsim was higher (101.0 +/- 22.6% vs. 69.7 +/- 12.9%; p < 0.05). Pretreatment of cardiomyocytes with the antioxidant ascorbic acid diminished the hypothermia-induced increase in intracellular ROS and prevented the beneficial effects of hypothermia on apoptosis and mitochondrial function.
  
  
  CONCLUSIONS
  Hypothermia at 31 degrees C can protect cardiomyocytes against oxidative stress-induced injury by decreasing apoptosis and mitochondrial dysfunction through intracellular ROS-dependent pathways.
authors: Department of Emergency Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin County.
authors: Chien-Hua
authors: CH
authors: Huang
authors: Huei-Wen
authors: HW
authors: Chen
authors: Min-Shan
authors: MS
authors: Tsai
authors: Chiung-Yuan
authors: CY
authors: Hsu
authors: Ren-How
authors: RH
authors: Peng
authors: Tzung-Dau
authors: TD
authors: Wang
authors: Wei-Tien
authors: WT
authors: Chang
authors: Wen-Jone
authors: WJ
authors: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000503:physiopathology / Q000628:therapy; D006861:Hydrogen Peroxide; D007036:Hypothermia, Induced; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide