A highly effective, rodent model of complete heart block by epicardial radiofrequency ablation

Figures

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  Fig. 1. Clear illustration of the surgical procedure. (A) Diagram showing the surgical profile of the rodent during thoracotomy and ablation ((A,B) produced using Biorender). (B) Cartoon depicting the fat pad ablation target (RAA = right atrial appendage, RV = right ventricle). (C) In-vivo image of the fat pad (CTA = cotton-tipped applicator). (D) The radio-frequency ablation system with arrows indicating the flow of energy. (E) Epicardial ablation tip consisting of a 12-gauge copper wire and saline irrigation sheath. (F) Configuration from Medtronic ablation catheter to 12-gauge copper wire for the epicardial ablation electrode. (G) Diagram for new epicardial ablation method.

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  Fig. 2. Disease model viability. (a) The study design indicates two weeks of ECG recordings before and after the CAVB model creation. ECG traces during pre-op (b), immediately post CAVB-ablation (c), and 28 days after model creation (d). Arrhythmias often appear on ECG as competing loci of escape rhythms (e), premature escape beats (f), and irregular escape rhythms (g). Blue-shaded areas identify the arrhythmia of interest.

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  Fig. 3. CAVB model beating rate trends. (a) Continuous beating rate averages 14 days before and after CAVB model creation using DSI telemetry, with standard deviation error bars (n = 5 SR; n = 4 CAVB). (b) Daily 5-minute beating rate averages for sinus rhythm for animals the 5 days leading up to CAVB creation and (c) CAVB animals 9–14 days post model creation. Note: Day 0 is the day of CAVB creation. The shaded segments (b,c) illustrate the 12-hour dark period, and the light segments represent the 12-hour light period in the animal facility. The dark line is the 5-minute heart rate average, and the blue lines represent their standard deviations.

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  Fig. 4. Survivability of CAVB procedures. Kaplan-Meier curve comparing survival trends of CAVB models created using epicardial ablations and subepicardial ablations. A statistical difference between the Kaplan–Meier survival curves was evaluated using the log-rank (Mantel–Cox) test, which yielded p < 0.001.

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  Fig. 5. Heart rate variability. HRV analysis for WT (n = 5) and CAVB (n = 4) models, day five post-surgery: (a) average RR intervals, (b) RMSSD, (c) SDNN and (d) SDRR for 1-hour light and dark periods with standard deviation error bars.

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  Fig. 6. Poincare analysis for beat-to-beat variability. (a) Poincare plots and beat-to-beat ∆RR for 1-hour light and dark periods for animals (n = 4) before and after CAVB creation, day five post-surgery. Black traces on Poincare plots indicate SD1 and SD2 values for each plot. (b) SD1, (c) SD2, and (d) SD1/SD2 values for the animals (n = 4) before and after CAVB creation, day five post-surgery, with standard deviation error bars.

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  Fig. 7. Effects of autonomic denervation on CAVB animals. One minute beating rate averages over time (n = 1), 10-minute mean heart rates before and after drug administration, and ∆ beating rates before and after administration of (A) 3 mg/kg atropine, (B) 3 mg/kg propranolol, or (C) 3 mg/kg atropine and 3 mg/kg propranolol in sinus rhythm (SR) (n = 5) and CAVB (n = 4) models. Bar graphs include standard error bars.