Dietary ω3 fatty acids modulate the substrate for post-operative atrial fibrillation in a canine cardiac surgery model.
OBJECTIVE
Pre-treatment with dietary ω3 polyunsaturated fatty acids (ω3-PUFA) has been reported to reduce the incidence of new-onset atrial fibrillation (AF) following cardiac surgery. In a canine cardiac surgery model, we evaluated the impact of dietary ω3-PUFA on atrial electrophysiological properties, inflammatory markers, the atrial endothelin-1 (ET-1) system, and the expression and distribution of connexin 43.


RESULTS
Adult mongrel dogs received either normal chow (NC, n = 11) or chow supplemented with fish oil (FO, 0.6 g ω3-PUFA/kg/day, n = 9) for 3 weeks before surgery. A left thoracotomy was performed, and the left atrial appendage (LAA) was excised. Atrial pacing/recording wires were placed, and the pericardium/chest was closed. The atrial ratio of ω6/ω3 lipids decreased from 15-20 in NC to 2-3 in FO. FO treatment lowered pre-surgical and stabilized post-surgical arachidonate levels. Peak neutrophil to lymphocyte ratio was lower and decayed faster in FO-treated animals. Extensive inflammatory cell infiltration was present in NC atria, but was reduced in FO-treated dogs. FO-treated animals had lower post-surgical atrial expression of inducible nitric oxide synthase (iNOS) and reduced plasma ET-1. Expression of ET-1 and inositol trisphosphate receptor type-2 proteins in the LAA was also reduced. FO treatment prolonged post-operative atrial effective refractory period, slowed heart rate, and enhanced heart rate variability. Importantly, AF (>30 s) was inducible in four of six NC dogs, but no FO dogs.


CONCLUSIONS
Dietary FO attenuated AF inducibility following cardiac surgery by modulating autonomic tone and heart rate. FO also reduced atrial inflammation, iNOS, and ET-1 expression.
Department of Molecular Cardiology, NE-61 Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Fadia
F
Mayyas
Seiichiro
S
Sakurai
Rashmi
R
Ram
Julie H
JH
Rennison
Eui-Seock
ES
Hwang
Laurie
L
Castel
Beth
B
Lovano
Marie-Luise
ML
Brennan
Douglas
D
Bibus
Bill
B
Lands
John
J
Barnard
Mina K
MK
Chung
David R
DR
Van Wagoner
D000818:Animals; D001281:Atrial Fibrillation / Q000517:prevention & control*; D002097:C-Reactive Protein / Q000032:analysis; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D018031:Connexin 43 / Q000032:analysis / Q000378:metabolism; D004285:Dogs; D019332:Endothelin-1 / Q000032:analysis; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006339:Heart Rate; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000032:analysis; D008055:Lipids / Q000097:blood; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D009195:Peroxidase / Q000032:analysis; D010766:Phosphorylation; D011183:Postoperative Complications / Q000517:prevention & control*; D017466:Receptors, Endothelin / Q000032:analysis
D018031:Connexin 43; D019332:Endothelin-1; D015525:Fatty Acids, Omega-3; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008055:Lipids; D017466:Receptors, Endothelin; D002097:C-Reactive Protein; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II