Therapeutic Hypothermia Reduces the Inflammatory Response Following Ischemia/Reperfusion Injury in Rat Hearts

Ther Hypothermia Temp Manag. 2017 Sep;7(3):162-170. doi: 10.1089/ther.2016.0042. Epub 2017 Mar 24.


Therapeutic hypothermia (TH) is known to protect against ischemia/reperfusion (I/R) injury. One mechanism of I/R injury includes secondary injury due to the inflammatory cascade. We hypothesized that TH reduces the inflammatory response following I/R injury. Rats were randomized to sham, normothermic, or hypothermic groups and subjected to 1 hour of coronary artery occlusion and 48 hours of reperfusion. Hypothermia was initiated, using the ThermoSuit® device, 2 minutes after the onset of coronary artery occlusion to a core temperature of 32°C, and then the rats were allowed to rewarm. After 48 hours, rats in the hypothermia group demonstrated a preserved left ventricular fractional shortening by echocardiography. TH decreased the inflammatory cytokines in the risk zone of the heart, which included monocyte chemoattractant protein-1, interleukin-6, tumor necrosis factor-α, and inducible nitric oxide synthase gene expression, and altered expression of the remodeling genes of matrix metalloproteinase and tissue inhibitor of metalloproteinase. Furthermore, rat inflammatory cytokines & receptors PCR array was performed and the data showed that 71 out of 84 genes were upregulated in the risk zone of normothermia hearts versus shams. The upregulation was largely reversed in the risk zone of hypothermia hearts compared to normothermia. TH preserves cardiac function, decreases excessive inflammatory gene expression, and regulates myocardial matrix remodeling related genes.

Keywords: hypothermia; inflammation; myocardial infarction.

MeSH terms

  • Animals
  • Cytokines / analysis
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Hypothermia, Induced*
  • Inflammation* / etiology
  • Inflammation* / metabolism
  • Inflammation* / therapy
  • Myocardial Reperfusion Injury* / complications
  • Myocardial Reperfusion Injury* / metabolism
  • Myocardial Reperfusion Injury* / therapy
  • Rats
  • Rats, Sprague-Dawley


  • Cytokines