| Background: Experimental and clinical studies both proved that the impact of atrial remodeling (including electrical and structural remodeling) and the effect of atrial autonomic nerve, especially the vagus, also played important roles in the occurance and maintain of atrial fibrillation (AF), except the effect of trigger foci from the pulmonary vein sleeves. It had been confirmed that pulmonary vein isolation (PVI) could eliminate the trigger foci of AF, however the contribution of PVI on atrial electrical remodeling (AER) and vagal modulation (including the vagal ganglion modulation) is still unknown. This study aimed to investigate the impact of PVI on the vagal modulation and the vulnerability of AF by the experimental study of monogeral dogs, furthermore to explore the effect of PVI on AER by the atrial short-time rapid pacing model. The distribution of the fat pad on the left atria was described, and the left atrial-pulmonary vein specimens with and without PVI procedure were stained by hematoxylin- eosin process and the anatonomic characters were analyzed in order to demonstrate the impairment of atrial vagal nerve thereby consummating the mechanism of PVI on AF therapy.Methods: 28 adult mongrel dogs under general anesthesia were randomized into group AER (groupA, n=10), group PVI (groupB, n=10) and group PVI+AER (groupC, n=8).①Multi polar catheters were placed into right atrial appendage (RAA), coronary sinus and right ventricle (RV) through right internal jugular vein and left femoral vein respectively. Ablation catheter and mapping catheter (Lasso) were put into left atrium via trans-septal procedure. Bilateral cervical sympathovagal trunks weredecentralized and the sympathetic effect was blocked by metoprolol administration.②In group B, the Sinus rhythm cycle length (SCL) were measured before and during vagal stimulation. And the vulnerability window (VW) of AF and Atrial effective refractory period (ERP) were both measured at four different sites of atria including right atrial appendage (RAA), left atrial appendage (LAA), the distal coronary sinus (CSd) and paroximal coronary sinus (CSp) with and without vagal stimulation. After PVI was performed around pulmonary vein ostium guided by Lasso catheter, the same parameters of SCL, VW, ERP shortening and ERP were measured with the same procedure as that before ablation. Furthmore the ERP shortening before and during VS were evaluated. Statistical tests were performed with SPSS software (version 11.0). Comparisons between the data obtained before and after PVI were performed with paired t-test.③In group A and C, The study protocols were all same except the PVI procedure in group C before the parameters tests. The Sinus rhythm cycle length (SCL) was measured before and during vagal stimulation. And the vulnerability window (VW) of AF and Atrial effective refractory period (ERP) were both measured at two different sites of atria including right atrial appendage (RAA) and left atrial appendage (LAA) with and without vagal stimulation. After the rapid pacing at right atrial at the rate of 600bpm for 30 minutes, same parameters of SCL, VW, ERP shortening and ERP were measured with the same procedure as that before atrial rapid pacing. Furthmore the ERP shortening before and and after pacing were evaluated. Statistical tests were performed with SPSS software (version 11.0), while the comparisons of the parameters recorded between the two different groups were performed by sample average t-test.④The distribution of the fat pad located on the left atria was described, and the least length from the fat pad to the ostium of PV were measured. The heart specimens in group A and C were obtained from the PV-left atria junction, and the specimens were fixed in 10% phosphate buffer formalin solution, embedded in paraffin, serially sectioned (5μm) transversely and longitudinally. Alternative sections were stained with hematoxylin-eosin solution and the anatomic characteristics were analyzed in order to demonstrate the impairment of atrial vagal nerve after ablation in group PVI.Results: Effects of PVI on vagal modulation: In group B,①SCL increased significantly during vagal stimulation before PVI(65±28 VS 142±15 bpm,P<0.001), while SCL remained unchanged during vagal stimulation after PV(I114±31 VS 135±19bpm,P>0.05).②Before PVI, ERP increased significantly before vagal stimulation compared with that during vagal stimulation (P<0.005 at RAA, P<0.05 at LAA, P<0.05 at CSd, P<0.001 at CSp). But after PVI, ERP remained unchanged with and without vagal stimulation (P>0.05 at RAA, P>0.05 at LAA, P>0.05 at CSd, P>0.05at CSp). AF was very difficult to be induced without vagal stimulation before and after PVI (VW close to 0), while VW of AF to vagal stimulation significantly decreased after PVI (11.11±10.33 VS 28.89±14.53 msec at RA, P<0.05; 0±0 VS 16.67±14.14msec at LAA, P<0.01; 1.11±0.33 VS 31.11±30.81msec at CSd, P<0.05; 1.11±0.33 VS 27.78±21.53msec at CSp, P<0.05).Effects of PVI on AER:①In group A, after rapid atrial pacing, ERP decreased significantly with vagal stimulation (P<0.001 at LAA; P<0.01 at RAA).and without vagal stimulation (P<0.05 at LAA; P<0.05 at RAA). AF was rarely induced without vagal stimulation before and after rapid atrial pacing (VW close to 0), while VW during vagal stimulation increased significantly after rapid atrial pacing (P<0.05 at LAA; P<0.01 at RAA).②In group C, ERP remained unchanged without vagal stimulation before and after rapid pacing (P=0.197 at LAA; P=0.451 at RAA), and ERP remained unchanged during vagal stimulation before and after rapid pacing (P=0.231 at LAA; P=0.104 at RAA). Atrial fibrillation was rarely induced both without vagal stimulation and during vagal stimulation before and after rapid atrial pacing (VW close to 0).③After rapid atrial pacing, shortening of ERP in group A was significant increased compared with that in group C (P<0.05 at LAA, P<0.005 at RAA without vagal stimulation; P<0.01at LAA, P<0.05 at RAA during vagal stimulation).Histopathological findings: The architecture of individual ganglion was significantly altered after ablation. In control specimens, the ganglion was connected to nerve fibres and surrounded by healthy adipose tissue. But after ablation, ganglionic capsule became incomplete. And there formed a gap between the ganglion and the surrounding adipose tissue.Conclusions:①The decreased ERP shortening and unchanged SCL to vagal stimulation after PVI indicates that PVI attenuates the vagal modulation to the atria. The decreased VW of AF by PVI indicates that attenuated vagal tone may contribute to the suppression of AF.②The radiofrequency energy of PVI could damaged the ganglion structure.③Atrial remodeling can decrease ERP and enhance the vagal modulation to atria, and PVI can release the atrial electrical remodeling. The atrial vagal denervation resulting from PVI maybe contributes to the attenuated atrial electrical remodeling. |
