p<0.0001 compared with before the operation

\* P<0.05 compared with the control group

‡ p<0.01 compared with before operation.

**Table 1.** Comparison of electrophysiological parameters (CT) between the control and PUFA groups before and after operation

#### **1.3. Inflammation and post cardiac surgery AF**

Although the pathophysiological mechanism underlying the genesis of post cardiac surgery AF has been the focus of many studies,it only remains partially understood. The inflamma‐ tory cascade and catecholamine surge associated with surgery have been thought of playing a prominent role in initiating AF after cardiac surgery. As a prototypic marker of inflamma‐ tion, CRP has been the focus of many studies, which is driven by the proinflammatory cyto‐ kines interleukin (IL)-1, tumor necrosis factor (TNF)-α, and IL-6(Bruins P et al.,1997) found that IL-6 rises initially and peaks at 6 h after cardiac surgery, and CRP levels increases and peaks on the second postoperative day of the cardiac surgery, with complement-CRP com‐ plexes levels peaking on the 2nd or 3rd postoperative day. The incidence of atrial arrhyth‐ mias similarly peaks on postoperative day 2 or 3. Other researchers have confirmed that IL-6 and CRP increased after cardiac surgery, with the incidence of atrial arrhythmias similarly peaking on the 2nd or 3rd postoperative day [13,14](Ishida K,et al.,2006;Kumagai K,et al., 2004). Many studies have related an increase in CRP and IL-6 in both paroxysmal AF and persistent AF, and concluded that CRP is not only associated with the presence of AF but may also predict an increased risk for future development of AF [15](Aviles RJ,et al.,2003). Other studies correlated leukocytosis to an increased incidence in AF in postoperative cardi‐ ovascular patients [16,17](Abdelhadi RH,et al.,2004;Lamm G,et al.,2006), and found that a more pronounced increase in postoperative WBC count will independently predict develop‐ ment of postoperative AF. Moreover, atrial inflammation of cardiac surgery effects on the electrical properties of atrial tissue, and the degree of atrial inflammation was associated with a proportional increase in the inhomogeneity of atrial conduction and AF duration [18] ( Ishii Y, et al.,2005). Administration of anti-inflammatory drugs (dexamethasone or corti‐ sone) significantly decreases the incidence of AF after cardiac surgery [19,20](Yred JP,et al., 2000;Halonen J,et al.,2007), which supports this inflammation-AF

hypothesis. The canine sterile pericarditis model can perfectly simulate inflammatory cir‐ cumstances of the post cardiac operation, by which AF can be induced and also peaks on the 2nd postoperative day [10](Page PL,et al.,1986). In this model, the multiple unstable reen‐ trant circuits were showed during AF, and it was critical for maintaining AF [10] (Page PL,et al.,1986). According to the multiple-wavelet hypothesis, atrial wavelength determines the number of wavelets, and the atrial wavelength is the product of AERP and the intra-atrial conduction velocity. So, the AERP and the intra-atrial conduction velocity have been thought to be important for the perpetuation of AF. In this canine sterile pericarditis model, we have evaluated CRP, IL-6 and TNF-α level on the baseline and on the 2nd postoperative day, and found that they all significantly increased in both groups. We simultaneously eval‐ uated the role of inflammation on atrial electrophysiological properties, and found that in‐ flammation can shorten AERPs and prolong intra-atrial CT in the canine sterile pericarditis model, which increased the inducibility and stability of AF. Our results are concordant with the previous results. Thus, in this model, elevated CRP, IL-6 and TNF-α were associated with sustained AF, suggesting that electrophysiological changes resulting from inflamma‐ tion perpetuate AF.

CT=conduction time; RAA=right atrial appendage; LRA=low lateral right atrium; HRA=high lateral right atrium; ARA=

**Table 1.** Comparison of electrophysiological parameters (CT) between the control and PUFA groups before and after

Although the pathophysiological mechanism underlying the genesis of post cardiac surgery AF has been the focus of many studies,it only remains partially understood. The inflamma‐ tory cascade and catecholamine surge associated with surgery have been thought of playing a prominent role in initiating AF after cardiac surgery. As a prototypic marker of inflamma‐ tion, CRP has been the focus of many studies, which is driven by the proinflammatory cyto‐ kines interleukin (IL)-1, tumor necrosis factor (TNF)-α, and IL-6(Bruins P et al.,1997) found that IL-6 rises initially and peaks at 6 h after cardiac surgery, and CRP levels increases and peaks on the second postoperative day of the cardiac surgery, with complement-CRP com‐ plexes levels peaking on the 2nd or 3rd postoperative day. The incidence of atrial arrhyth‐ mias similarly peaks on postoperative day 2 or 3. Other researchers have confirmed that IL-6 and CRP increased after cardiac surgery, with the incidence of atrial arrhythmias similarly peaking on the 2nd or 3rd postoperative day [13,14](Ishida K,et al.,2006;Kumagai K,et al., 2004). Many studies have related an increase in CRP and IL-6 in both paroxysmal AF and persistent AF, and concluded that CRP is not only associated with the presence of AF but may also predict an increased risk for future development of AF [15](Aviles RJ,et al.,2003).

anterior right atrium.

operation

†p<0.05 compared with before the operation # p<0.0001 compared with before the operation

48 Atrial Fibrillation - Mechanisms and Treatment

\* P<0.05 compared with the control group ‡ p<0.01 compared with before operation.

**1.3. Inflammation and post cardiac surgery AF**

#### **1.4. Other potential mechanisms of antiarrhythmic action of n-3 PUFA administration**

The current hypotheses of n-3 PUFAs in preventing AF are based on their inhibiting ca‐ pacity of some ion channels. Previous studies have demonstrated that n-3 PUFAs have capacity to inhibit fast, voltage dependent sodium currents, L-type calcium currents, the Na /Ca2 exchanger, which might prevent delayed after-depolarizations and triggered ac‐ tivity, as well as their class III antiarrhythmic-like effect on Kv1.5 channel (IKUR current present in the atrium) [36,37](Xial YF,et al.,2004;Honore E,et al.,1994). Other studies found n-3 PUFAs can attenuate atrial structural remodeling not only by activating matrix metalloproteinase-9 mRNA expression and attenuating of collagen turnover [38](Laurent G,et al.,2008), but also by modulating of atrial gap junction protein CX40 and CX43 [39] (Sarrazin JF,et al.,2007). Otherwise, evidence suggests that n-3 fatty acids consumption at‐ tenuates oxidative stress in humans, and the underlying mechanisms may lead to sup‐ pressed production of reactive oxygen species by leukocytes, inhibition of the prooxidant enzyme phospholipase A2, and induction of antioxidant enzymes [40](Mori TA,et al.,2003).
