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J Thorac Cardiovasc Surg 2006;132:72-79
© 2006 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

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

^a Department of Surgery, The Royal College of Surgeons in Ireland, Dublin, Ireland
^b Department of Clinical Pharmacology, The Royal College of Surgeons in Ireland, Dublin, Ireland
^c Department of Statistics, Faculty of Science, Garyounis University, Benghazi, Libya.

Read at the Eighty-fifth Annual Meeting of The American Association for Thoracic Surgery, San Francisco, Calif, April 10-13, 2005.

Received for publication April 7, 2005; revisions received September 25, 2005; accepted for publication October 11, 2005.

^_* Address for reprints: Professor J. M. Redmond, Department of Surgery, RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland. (Email: jmdredmond{at}eircom.net).

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 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).

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.

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