Neural substrate of posterior left atrium: A novel modulation for inducibility and remodeling of atrial fibrillation in canine

Abstract

BackgroundThe neural mechanism of posterior left atrium (PLA) for genesis of atrial fibrillation has not been completely elucidated. We sought to assess the contribution of PLA denervation on atrial fibrillation (AF) inducibility and atrial remodeling.Methods and resultsAfter left thoracotomy in anesthetized dogs (n = 32), electrode catheters were attached to the PLA, left atrial roof, left pulmonary vein and left atrial appendage. Experiment 1 (n = 16): Vagal stimulation (VS group, n = 8) led to more pronounced ERP shortening in PLA than in other sites (CTL:71±7 ms vs VS: 52±6 ms, P<0.05;). Compared with control group (CTL group, n = 8), atropine alone or with propranolol applied to PLA greatly inhibited VS-induced ERP shortening, ERP dispersion increase, and AF inducibility in the left atrium (P<0.05); but ERP was not significantly different between atropine alone and DB conditions (Atro:85±8 ms vs DB:90±9ms, P>0.05). In addition, domain frequency (DF) of VS-induced AF waveform was not affected by atropine alone, while selective double autonomic blockade at PLA significantly decreased DF at all sites (P<0.05). Experiment 2 (n = 16): In group 1 (n = 8), ERP was markedly shortened in the first 2 hours (11–19% decrease) and then stabilized; however, WOV was progressively widened throughout the 6 hours rapid atrial pacing (BS: 51±9ms vs 6th hour: 161±30ms, P<0.05). After drug application, ERP was increased in all sites of atria, the ERP dispersion was significantly decreased (Atro: 2.36±0.02 vs 6th hour: 5.09±0.07, P<0.05) and AF could be induced in only 1 of 8 dogs. In group 2 (n = 8), 6 hours rapid atrial pacing failed to shorten the ERP and increased ERP dispersion, and only 2 episodes of AF could be induced (WOV = 0).ConclusionLocal denervation of PLA, as predominant atrial autonomic profile, greatly inhibits AF inducibility and atrial remodeling.

The cardiac autonomic nervous system: A target for modulation of atrial fibrillation

“…The density of nerve fibers in PV-LA junction is significantly higher than PV distal parts, and the sympathetic innervation appears to be superior. The regional differences in the conduction velocity and ERP of PLA and PV-LA as a result of anatomical properties [31][32][33] Notably, our study 38 also confirmed that intervention of PV ostium (including: RSPV anterior wall and LSPV apex, etc.) with radiofrequency ablation can produce significant vagal reactions manifested by sinus arrest and atrioventricular conduction delay; modification of this region can significantly decrease the postoperative recurrence rate (Figure 4).…”

“…CANS is a highly integrated network, where the highly activated GP can release neurotransmitters by a proximal‐to‐distal gradient. The activation of axons from GP will then reversely activate the distant GP, thus leading to neurotransmitter release and inducing AF, which was explained by Sunny Po et al with the “octopus hypothesis.” Recent studies indicate that multiple intra‐atrial regions are innervated by the nerve fibers from GP, called atrial innervation region (IR) . However, the innervation function of IR is spatially heterogeneous, that is, the density of nerve fibers, M receptors and I K,Ach channel in the PLA and the junction of PV ostium and left atrium (PV‐LA) is greater than that in other left atrial regions; Tan et al also demonstrated that autonomic nerve density was highest in the LA within 5 mm of the PV‐LA junction by immunohistochemical staining on segments from normal human hearts .…”

“…The density of nerve fibers in PV‐LA junction is significantly higher than PV distal parts, and the sympathetic innervation appears to be superior. The regional differences in the conduction velocity and ERP of PLA and PV‐LA as a result of anatomical properties provide an important condition for the formation and spreading of driving rotor in atria. Using frequency‐domain analysis, Kalifa et al found that 80% of the maximal dominant frequency (DF max ) sites of AF were located in the junction of PLA and PV, and that the rotor could stably anchor in this region, which was manifested by the DF max sites with relatively high regularity index.…”

“…Using frequency‐domain analysis, Kalifa et al found that 80% of the maximal dominant frequency (DF max ) sites of AF were located in the junction of PLA and PV, and that the rotor could stably anchor in this region, which was manifested by the DF max sites with relatively high regularity index. Arora et al and our previous study demonstrated that intervention of PLA with autonomic nerve blockers could extend the local ERP, lower atrial ERP dispersion and significantly reduce the induction rate and duration of AF.…”

“…30 Recent studies indicate that multiple intra-atrial regions are innervated by the nerve fibers from GP, called atrial innervation region (IR). [31][32][33] However, the innervation function of IR is spatially heterogeneous, that is, the density of nerve fibers, M receptors and I K,Ach channel in the PLA and the junction of PV ostium and left atrium (PV-LA) is greater than that in other left atrial regions; Tan et al also demonstrated that autonomic nerve density was highest in the LA within 5 mm of the PV-LA junction by immunohistochemical staining on segments from normal human hearts. 34 But the purpose of this innervation in normal hearts still remains unclear.…”