Intravenous omega-3, a technique to prevent an excessive innate immune response to cardiac surgery in a rodent gut ischemia model.
OBJECTIVE
Neutrophil infiltration of tissues as part of the inflammatory response to cardiac surgery is one of the major mediators of postoperative multiple-organ dysfunction. Omega-3 fatty acids markedly attenuate endothelial cell inflammatory responses, including upregulation of neutrophil adhesion molecules. The efficacy of a clinically safe form of omega-3 to produce this effect in vivo was examined.


METHODS
Rat gut intravital microscopic analysis was used to visualize neutrophil transmigration from the microcirculation into the tissues of the gut. Inflammatory activation was in the form of 30 minutes of ischemia and 90 minutes of reperfusion. Sham, control (0.9% saline infusion over 4 hours), and omega-3 (Omegaven [Fresenius Kabi, Bad Homburg, Germany] infusion over 4 hours) pretreatments were compared.


RESULTS
Ischemia-reperfusion resulted in a 4-fold increase in neutrophil adherence to the endothelium (baseline: 4.3 ± 0.2 vs control group: 19.2 ± 3.5 adherent neutrophils per 100 μm, P < .01), which intravenous omega-3 suppressed (7.8 ± 1.7 adherent neutrophils per 100 μm, P < .01). Omega-3 pretreatment also reduced neutrophil transmigration into the tissues after reperfusion (sham group: 6.3 ± 0.8 vs control group: 13.2 ± 1.4 vs omega-3 group: 9.4 ± 0.9 neutrophils per field, P = .037). Gut tissue levels of the neutrophil-released enzyme myeloperoxidase were similarly markedly reduced with omega-3 pretreatment (sham group: 10.5 ± 1.6 vs control group: 19.0 ± 3.3 vs omega-3 group: 10.1 ± 1.2 U/g, P = .03).


CONCLUSIONS
Four hours' pretreatment with a relatively safe form of intravenous omega-3 suppressed neutrophil adherence and tissue infiltration, resulting in lower levels of the tissue-damaging enzyme myeloperoxidase. This suggests a possible strategy for diminishing postoperative multiple-organ dysfunction.
Byrne
John
J
Department of Surgical Research, the Royal College of Surgeons in Ireland, Dublin, Ireland.
McGuinness
Jonathan
J
Chen
Gang
G
Hill
Arnold D K
AD
Redmond
Mark J
MJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D007113:Immunity, Innate / Q000187:drug effects*; D007262:Infusions, Intravenous; D007422:Intestines / Q000098:blood supply*; D036904:Leukocyte Rolling / Q000187:drug effects; D008297:Male; D018715:Microscopy, Video; D018375:Neutrophil Activation / Q000187:drug effects; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D015525:Fatty Acids, Omega-3; D009195:Peroxidase