Canine Rapid Atrial Pacing Model Research Articles

Regions of Highly Recurrent Electrogram Morphology With Low Cycle Length Reflect Substrate for Atrial Fibrillation

Traditional anatomically guided ablation and attempts to perform electrogram-guided atrial fibrillation (AF) ablation (CFAE, DF, and FIRM) have not been shown to be sufficient treatment for persistent AF. Using biatrial high-density electrophysiologic mapping in a canine rapid atrial pacing model of AF, we systematically investigated the relationship of electrogram morphology recurrence (EMR) (Rec% and CLR) with established AF electrogram parameters and tissue characteristics. Rec% correlates with stability of rotational activity and with the spatial distribution of parasympathetic nerve fibers. These results have indicated that EMR may therefore be a viable therapeutic target in persistent AF.

NCC-3902, a novel late sodium current blocker, exhibits potent antiarrhythmic effect in isolated guinea pig pulmonary vein and canine rapid atrial pacing model

NCC-3902, a novel late sodium current blocker, exhibits potent antiarrhythmic effect in isolated guinea pig pulmonary vein and canine rapid atrial pacing model

Cilostazol Prevents Atrial Structural Remodeling through the MEK/ERK Pathway in a Canine Model of Atrial Tachycardia

Objectives: Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. Atrial structural remodeling (ASR), particularly atrial fibrosis, is an important contributor to the AF substrate. This study aimed to investigate the preventive effects of the phosphodiesterase 3 inhibitor cilostazol on ASR and its potential molecular mechanisms in a canine model of rapid atrial pacing (RAP). Methods: Thirty dogs were assigned to sham (Sham), paced/ no treatment (Paced) and paced + cilostazol 5 mg/kg/day (Paced + cilo) groups, with 10 dogs in each group. RAP at 500 beats/min was maintained for 2 weeks, while the Sham group was instrumented without pacing. Cilostazol was provided orally during pacing. Western blotting, RT-PCR and pathology were used to assess ASR. Results: Cilostazol attenuated atrial interstitial fibrosis and structural remodeling in canines with RAP. MEK/ERK transduction pathway gene expression was upregulated in the Paced group compared with the Sham group. Cilostazol markedly alleviated these changes in the MEK/ERK pathway. Transforming growth factor-β₁ protein expression in the Paced group was significantly higher than in the Sham group (p < 0.01), and was significantly reduced by cilostazol (p < 0.01). Conclusions: Our findings suggest that cilostazol is beneficial for prevention and treatment in atrial tachycardia-induced ASR in a canine model of RAP.

Abstract 15840: Electrogram Morphology Recurrence Analysis Identifies Areas of Consistent Activation Directions and Rotor Activity in a Rapid Atrial Pacing Model of Atrial Fibrillation

Introduction: Electrogram morphology recurrence (EMR) analysis is a novel mapping technique which characterizes morphology patterns during atrial fibrillation (AF). Using high resolution electrical mapping, we tested the hypothesis that EMR analysis could identify areas of consistent activation directions and rotor activity in a canine rapid atrial pacing model of AF. Methods: Three weeks of rapid right atrial pacing (600 bpm) was performed in six dogs. A triangular plaque was used to obtain 117 simultaneous bipolar AF electrograms from two right and three left atrial locations. EMR plots for each electrogram recording were created by cross-correlation of each activation waveform with each other. The percentage of the most common morphology (REC%) and the mean cycle length (CL) of activations with the most common morphology (CLR) were computed. Activation pattern for each site was classified as either having stable rotors, passive activity, or chaotic activity. Activation vectors were computed and a vector index (VI) was used to measure vector consistency. Results: Figure A shows an example of an EMR plot map from recordings in the left atrium with red indicating areas of high EMR. The sites with the shortest CL had an average CL of 81±13 ms. The sites with the highest REC% had an average value of 99±2%. The sites with the shortest CLR had an average value of 91±17 ms. REC% was highly correlated with VI (Figure B). Minimum CL was only moderately shorter in rotor sites compared to chaotic and passive sites (Figure C). Maximum REC% was significantly higher in rotors sites than in chaotic sites, but not different from passive sites (Figure D). Minimum CLR in the rotor sites were significantly less than both the chaotic and passive sites (Figure E). Conclusions: EMR analysis is a new mapping technique that correlates well with activation vector consistency and can identify rotor activity. This is a promising method for mapping AF that may identify sources that can be targeted for ablation.

Effect of nifekalant on acute electrical remodelling in rapid atrial pacing canine model

Nifekalant may prevent atrial fibrillation (AF) and possibly be useful in treatment of atrial tachyarrhythmia in patients with severe heart failure. This study investigated the electophysiologic effect of nifekalant on the acute atrial remodeling in rapid atrial pacing (RAP) model of canine. Twelve mongrel dogs subjected to rapid stimulation (400 beats/min) at left atrial appendage (LAA) for 24 hours, were randomized into the control group (rapid pacing only, n = 6) and the nifekalant group (intravenous nifekalant therapy immediately after RAP, n = 6). Atrial electrophysiological parameters were measured in right atrium, coronary sinus, LAA, posterior wall of left atrium (PWLA) and left superior pulmonary vein (LSPV), before and after the RAP. In the control group, the effective refractory periods (ERP) were shortened greatly at all sites, paced dogs had substantially shorter ERPs in the high right atrium, LAA, and LSPV, but fewer changes in the PWLA, the coefficient variation of ERP (COV ERP) was increased significantly. After rapid atrial stimulation, the inducibility of AF increased significantly [induction number: pre-RAP vs post-RAP, 1.00 +/- 0.89 vs 8.17 +/- 2.79, P < 0.01; duration of AF: pre-RAP vs post-RAP, (450.34 +/- 362.59) ms vs (9975.77 +/- 4376.99) ms, P < 0.01]. In the nifekalant group, although the ERPs were prolonged at all sites compared with those in pre-RAP state, only the value at LSPV differed significantly from that in pre-RAP state [pre-RAP vs post-RAP, (102.50 +/- 5.24) ms vs (132.51 +/- 5.20) ms, P < 0.01]; the COV ERP did not change statistically in this group. The inducibility of AF slightly increased but insignificantly after pacing [induction number: pre-RAP vs post-RAP, 0.83 +/- 0.75 vs 1.67 +/- 0.82, P = 0.19; duration of AF: pre-RAP vs post-RAP, (378.67 +/- 317.88) ms vs (1124.08 +/- 1109.77) ms, P = 0.06]. Conduction time values did not alter significantly in either of the two groups after RAP. In canine RAP model, nifekalant inhibited ERP shortening and ERP heterogeneity increasing, decreased AF induction. Nifekalant can reverse acute electrical remodeling effect in this model.

Direction-dependent conduction abnormalities in a canine model of atrial fibrillation due to chronic atrial dilatation

Chronic rapid atrial pacing (RAP) leads to changes that perpetuate atrial fibrillation (AF). Chronic atrial dilatation due to mitral regurgitation (MR) also increases AF inducibility, but it is not clear whether the underlying mechanism is similar. Therefore, we have investigated atrial electrophysiology in a canine MR model (mitral valve avulsion, 1 mo) using high-resolution optical mapping and compared it with control dogs and with the canine RAP model (6-8 wk of atrial pacing at 600 beats/min, atrioventricular block, and ventricular pacing at 100 beats/min). At followup, optical action potentials were recorded using a 16 x 16 photodiode array from 2 x 2-cm left atrial (LA) and right atrial (RA) areas in perfused preparations, with pacing electrodes around the field of view to study direction dependency of conduction. Action potential duration at 80% repolarization (APD(80)) was not different between control and MR but was reduced in RAP atria. Conduction velocities during normal pacing were not different between groups. However, the MR LA showed increased conduction heterogeneity during pacing at short cycle lengths and during premature extrastimuli, which frequently caused pronounced regional conduction slowing. Conduction in the MR LA during extrastimulation also displayed a marked dependence on propagation direction. These phenomena were not observed in the MR RA and in control and RAP atria. Thus both models form distinctly different AF substrates; in RAP dogs, the decrease in APD(80) may stabilize reentry. In MR dogs, regional LA conduction slowing and increased directional dependency, allowing unidirectional conduction block and preferential paths of conduction, may account for increased AF inducibility.

1034-208 Enalapril can prevent perpetuation of atrial fibrillation through suppression of interstitial fibrosis and connex 43 expression associated with shortening of excitable gap in a canine rapid atrial pacing model with tachycardia mediated cardiomyopathy

1034-208 Enalapril can prevent perpetuation of atrial fibrillation through suppression of interstitial fibrosis and connex 43 expression associated with shortening of excitable gap in a canine rapid atrial pacing model with tachycardia mediated cardiomyopathy