Myocardial protection using an omega-3 fatty acid infusion: quantification and mechanism of action.

Abstract

OBJECTIVES:

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: J McGuinness, T G Neilan, A Sharkasi, D Bouchier-Hayes, J M Redmond
• Journal: The Journal of thoracic and cardiovascular surgery (J Thorac Cardiovasc Surg) Vol. 132 Issue 1 Pg. 72-9 (Jul 2006) ISSN: 1097-685X [Electronic] United States
• PMID: 16798305 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acids, Omega-3
• Fatty Acids, Unsaturated
• HSP72 Heat-Shock Proteins
• Docosahexaenoic Acids
• 8-epi-prostaglandin F2alpha
• Arachidonic Acid
• Malondialdehyde
• Eicosapentaenoic Acid
• Dinoprost

Topics

• Animals
• Arachidonic Acid (analysis)
• Blotting, Western
• Cell Membrane (chemistry)
• Dinoprost (analogs & derivatives, metabolism)
• Disease Models, Animal
• Docosahexaenoic Acids (analysis)
• Eicosapentaenoic Acid
• Fatty Acids, Omega-3 (administration & dosage, metabolism, pharmacology)
• Fatty Acids, Unsaturated (analysis)
• HSP72 Heat-Shock Proteins (analysis, metabolism)
• Immunohistochemistry
• Infusions, Intravenous
• Ischemic Preconditioning, Myocardial (methods)
• Male
• Malondialdehyde (analysis)
• Myocardial Reperfusion Injury (physiopathology, prevention & control)
• Myocardium (chemistry)
• Oxidation-Reduction
• Oxidative Stress
• Rabbits
• Up-Regulation
• Ventricular Function, Left