title: Cardioprotection of 17,18-epoxyeicostetraenoic acid in ischemia/reperfusion is mediated by cyclooxygenase-2: a study in a rat model.
abstract: OBJECTIVE
  Arachidonic acid and related cardioprotective eicosanoids are released in myocardial ischemia/reperfusion injury. The present study analyzes the effects of the eicosapentaenoic acid derived 17,18-epoxyeicostetraenoic acid on isolated cardiomyocytes and investigates whether 17,18-epoxyeicostetraenoic acid serves as a potential factor in the cardio-depressant postischemic effluent.
  
  
  METHODS
  After 10 minutes of global ex vivo stop-flow ischemia, adult rat hearts were reperfused and coronary postischemic effluent was collected over a period of 30 seconds. Nonischemic effluent was collected prior to ischemia. The effects of 17,18-epoxyeicostetraenoic acid on calcium (Ca(2+)) metabolism and contraction frequency of isolated neonatal rat cardiomyocytes were tested and compared with the effects of prior collected postischemic and nonischemic effluents. Isolated neonatal cardiomyocytes were preincubated with selective (NS-398, SC-560) and nonselective cyclooxygenase inhibitors (indomethacin) to determine whether cardio-depressive effects are mediated by cyclooxygenase.
  
  
  RESULTS
  In contrast to the nonischemic effluent, both 17,18-epoxyeicostetraenoic acid and the postischemic effluent induced a comparable decrease of the Ca(2+) transient and the contraction frequency (P < .05 vs control). The cardio-depressive effects of 17,18-epoxyeicostetraenoic acid and the postischemic effluent were significantly attenuated after preincubation with the unselective cyclooxygenase inhibitor indomethacin and the selective cyclooxygenase-2 inhibitor NS-398 (P < .05 vs control). Selective cyclooxygenase-1 inhibition with SC-560 did not influence the effect of 17,18-epoxyeicostetraenoic acid and the postischemic effluent.
  
  
  CONCLUSIONS
  Our data show that the cardio-depressive effects of 17,18-epoxyeicostetraenoic acid are comparable with the postischemic effluent and are mediated by cyclooxygenase-2. Our results suggest a potential cardioprotective role of the eicosanoid 17,18-epoxyeicostetraenoic acid in heart ischemia/reperfusion injury.
authors.affiliation: Department of Internal Medicine B, Ernst-Moritz-Arndt-University, Greifswald, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmelzle
authors.forename: S B
authors.initials: SB
authors.lastname: Felix
authors.forename: A
authors.initials: A
authors.lastname: Staudt
authors.forename: L R
authors.initials: LR
authors.lastname: Herda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D001095:Arachidonic Acids; C070378:17,18-epoxy-5,8,11,14-eicosatetraenoic acid; D051546:Cyclooxygenase 2