title: Myocardial protection using an omega-3 fatty acid infusion: quantification and mechanism of action.
abstract: OBJECTIVE
  Omega-3 fatty acids exhibit anti-inflammatory, antithrombotic, and antiarrhythmic properties. We investigated the extent and underlying mechanism of protection conferred by a pre-emptive omega-3 infusion in a model of regional cardiac ischemia-reperfusion injury.
  
  
  METHODS
  New-Zealand White rabbits received either the omega-3 infusion or a control infusion of 0.9% saline (n = 14 in each group). The large marginal branch of the left coronary artery was occluded for 30 minutes, cardiac function was assessed during 3 hours of reperfusion, and infarct size was measured. Pretreatment-induced alterations in myocardial membrane fatty acid composition and intramyocardial heat shock protein 72 were additionally assessed (n = 5 in each group). Serum markers of myocardial membrane oxidative stress, malonaldehyde and 8-isoprostane, were also determined. Results are expressed as means +/- standard error of the mean and significance was tested with analysis of variance.
  
  
  RESULTS
  Pretreatment increased myocardial membrane omega-3 fatty acid content 5-fold, from 0.94% +/- 0.07% in controls to 5.38% +/- 0.44% in the omega-3 group (P < .01), and it produced a 225% elevation of levels of heat shock protein 72 (P = .019) before ischemia-reperfusion. This was associated with a 40% reduction in infarct size (P < .01). Whereas the reperfusion-induced rise in malonaldehyde levels was higher with omega-3 pretreatment, 10.2 +/-1.5 micromol/L versus 6.1 +/- 0.7 micromol/L in controls (P = .04), 8-isoprostanes showed a 9-fold reduction, 679 +/- 190 pg/mL in controls vs 74 +/- 45 pg/mL in the omega-3 group (P = .0077).
  
  
  CONCLUSIONS
  A pre-emptive omega-3 infusion significantly reduces infarct size through the dual mechanisms of upregulation of heat shock protein 72, a key preconditioning protein, and a dramatic increase in the omega-3 content of myocardial membranes, which appears to facilitate a shift in oxidant ischemia-reperfusion injury. Further study to optimally shorten the pretreatment regimen for this potentially acceptable infusion will now be pursued.
authors.affiliation: Department of Surgery, The Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: McGuinness
authors.forename: T G
authors.initials: TG
authors.lastname: Neilan
authors.forename: A
authors.initials: A
authors.lastname: Sharkasi
authors.forename: D
authors.initials: D
authors.lastname: Bouchier-Hayes
authors.forename: J M
authors.initials: JM
authors.lastname: Redmond
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000032:analysis; D015153:Blotting, Western; D002462:Cell Membrane / Q000737:chemistry; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000032:analysis; D015118:Eicosapentaenoic Acid; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D050884:HSP72 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011817:Rabbits; D015854:Up-Regulation; D016277:Ventricular Function, Left
chemical_list: D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D050884:HSP72 Heat-Shock Proteins; D004281:Docosahexaenoic Acids; C075750:8-epi-prostaglandin F2alpha; D016718:Arachidonic Acid; D008315:Malondialdehyde; D015118:Eicosapentaenoic Acid; D015237:Dinoprost