Remote myocardial injury: the protective role of fluoxetine

Can J Physiol Pharmacol. 2018 Apr;96(4):319-327. doi: 10.1139/cjpp-2017-0383. Epub 2017 Sep 15.

Abstract

Aortic cross-clamping-induced ischemia-reperfusion (IR) is an important factor in the development of postoperative acute cardiac injury following abdominal aortic surgery. We investigated the possible anti-oxidant/anti-inflammatory effects of fluoxetine (FLX), which is used widely as a preoperative anxiolytic on cardiac injury induced by IR of the infrarenal abdominal aorta. FLX was administered to IR-performed (60 min of ischemia and 120 min of reperfusion) rats for 3 days, once daily at 20 mg/kg i.p. dosage. Results were compared to control and non-FLX-treated IR-performed rats. Serum creatine kinase (CK) and CK-MB levels, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels in the IR group were significantly higher whereas superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels were lower than for the control. IR also increased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1β, and interleukin-6 and decreased interleukin-10 levels. FLX decreased CK, CK-MB, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels while increasing superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels. FLX also decreased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels and increased interleukin-10 levels compared to IR. FLX attenuated the morphological changes associated with cardiac injury. Our study clearly demonstrates that FLX confers protection against aortic IR-induced cardiac injury, tissue leucocyte infiltration, and cellular integrity via its anti-oxidant/anti-inflammatory effects.

Keywords: acute cardiac injury; aorte abdominale infra-rénale; fluoxetine; fluoxétine; inflammation; infrarenal abdominal aorta; ischemia–reperfusion; ischémie–reperfusion; lésions cardiaques aiguës; oxidant/anti-oxidant balance; oxidative stress; stress oxydatif; équilibre oxydation/anti-oxydation.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Biomarkers / metabolism
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Creatine Kinase / metabolism
  • Cytokines / metabolism
  • Fluoxetine / pharmacology
  • Fluoxetine / therapeutic use*
  • Hemodynamics / drug effects
  • Iron / metabolism
  • Lipid Peroxides
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Oxidants / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Peroxidase / metabolism
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Antioxidants
  • Biomarkers
  • Cardiotonic Agents
  • Cytokines
  • Lipid Peroxides
  • Oxidants
  • Thiobarbituric Acid Reactive Substances
  • Fluoxetine
  • Iron
  • Peroxidase
  • Creatine Kinase