title: Lipid peroxidation, arachidonic acid and products of the lipoxygenase pathway in ischaemic preconditioning of rat heart.
abstract: OBJECTIVE
  Preconditioning with brief intermittent periods of ischaemia is known to provide protection against ischaemic injury. It has been suggested that myocardial ischaemia also activates phospholipase A2, which releases arachidonic acid from phospholipids. In the present study the possible role of phospholipid peroxidation, arachidonic acid and products of the lipoxygenase pathway in cellular mechanisms of ischaemic preconditioning was examined.
  
  
  METHODS
  Isolated, buffer-perfused rat hearts were freeze-clamped at the end of preconditioning (a cycle of 5 min global ischaemia +5 min reperfusion) and at the end of 30 min global ischaemia and analysed for non-esterified fatty acids and fatty acids in the 2-position of phospholipid. In a separate set of experiments, hearts pretreated with a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), were subjected to 30 min regional ischaemia and 120 min reperfusion. Infarct size was determined by tetrazolium staining and the ischaemic risk zone with fluorescent particles.
  
  
  RESULTS
  Myocardial levels of arachidonic as well as of linoleic and docosahexaenoic acid were significantly elevated by preconditioning. Also, the level of peroxidized polyunsaturated fatty acids (measured as hydroxy conjugated dienes) in myocardial phospholipid was significantly increased: 101.4 +/- 16.8 nmol/g versus 51.2 +/- 7.3 nmol/g tissue dw in the control group, p < 0.05. Pre-treatment of hearts with 5 microM NDGA blocked the infarct limiting effects of preconditioning: infarct size was 37.4 +/- 6.4% of risk zone in control, 9.0 +/- 0.9% in the preconditioning group and 27.7 +/- 3.8% in the preconditioning + NDGA group (p < 0.05 vs. i.p., n.s. vs. control).
  
  
  CONCLUSIONS
  Our findings provide evidence for the involvement of phospholipase A2 and lipoxygenase derived lipid second messengers in ischaemic preconditioning of the isolated rat heart.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Tartu, Estonia. joels@fagmed.uit.no
authors.forename: J
authors.initials: J
authors.lastname: Starkopf
authors.forename: T V
authors.initials: TV
authors.lastname: Andreasen
authors.forename: E
authors.initials: E
authors.lastname: Bugge
authors.forename: K
authors.initials: K
authors.lastname: Ytrehus
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000032:analysis; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D019157:Ischemic Preconditioning, Myocardial; D008041:Linoleic Acids / Q000032:analysis; D015227:Lipid Peroxidation; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D009203:Myocardial Infarction / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D010477:Perfusion; D010743:Phospholipids / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D016859:Lipoxygenase Inhibitors; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D009637:Masoprocol; D008084:Lipoxygenase