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

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 132; no. 1; pp. 72 - 79.e1
• Main Authors: McGuinness, J., Neilan, T.G., Sharkasi, A., Bouchier-Hayes, D., Redmond, J.M.
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.07.2006; AATS/WTSA
• Subjects: Animals; Arachidonic Acid - analysis; Blotting, Western; Cell Membrane - chemistry; Dinoprost - analogs & derivatives; Dinoprost - metabolism; Disease Models, Animal; Docosahexaenoic Acids - analysis; Eicosapentaenoic Acid; Fatty Acids, Omega-3 - administration & dosage; Fatty Acids, Omega-3 - metabolism; Fatty Acids, Omega-3 - pharmacology; Fatty Acids, Unsaturated - analysis; HSP72 Heat-Shock Proteins - analysis; HSP72 Heat-Shock Proteins - metabolism; Immunohistochemistry; Infusions, Intravenous; Ischemic Preconditioning, Myocardial - methods; Male; Malondialdehyde - analysis; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - chemistry; Oxidation-Reduction; Oxidative Stress; Rabbits; Up-Regulation; Ventricular Function, Left; LVEDP; dP/dt min; dP/dt max; HSP; 16; 17; 30; 31; LVESP
• ISSN: 0022-5223; 1097-685X
• DOI: 10.1016/j.jtcvs.2005.10.061

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. 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. 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 μmol/L versus 6.1 ± 0.7 μmol/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). 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.