Permanent and Transient Electrophysiological Effects During Cardiac Cryoablation Documented by Optical Activation Mapping and Thermal Imaging.

OBJECTIVE: Cardiac catheter cryoablation is a safer alternative to radiofrequency ablation for arrhythmia treatment, but electrophysiological (EP) effects during and after freezing are not adequately characterized. The goal of this study was to determine transient and permanent temperature induced EP effects, during and after localized tissue freezing. METHODS: Conduction in right (RV) and left ventricles (LV) was studied by optical activation mapping during and after cryoablation in paced, isolated Langendorff-perfused porcine hearts. Cryoablation was performed endocardially (n=4) or epicardially (n=4) by a cryoprobe cooled to -120 °C for 8 minutes. Epicardial surface temperature was imaged with an infrared camera. Viability staining was performed after ablation. Motion compensation and co-registration was performed between optical mapping data, temperature image data, and lesion images. RESULTS: Cryoablation produced lesions 14.9 +/- 3.1 mm in diameter and 5.8 +/- 1.7 mm deep. A permanent lesion was formed in tissue cooled below -5 +/- 4 °C. Transient EP changes observed at temperatures between 17 and 37 °C during cryoablation surrounding the frozen tissue region directly correlated with local temperature, and include action potential (AP) duration prolongation, decrease in AP magnitude, and slowing in conduction velocity (Q10=2.0). Transient conduction block was observed when epicardial temperature reached <17 °C, but completely resolved upon tissue rewarming, within 5 minutes. CONCLUSION: Transient EP changes were observed surrounding the permanent cryo lesion (<-5 °C), including conduction block (-5 to 17 °C), and reduced conduction velocity (>17 °C). SIGNIFICANCE: The observed changes explain effects observed during clinical cryoablation, including transient increases in effective refractory period, transient conduction block, and transient slowing of conduction. The presented quantitative data on temperature dependence of EP effects may enable the prediction of the effects of clinical cryoablation devices.

Spinal cord stimulation protects against atrial fibrillation induced by tachypacing.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to modulate atrial electrophysiology and confer protection against ischemia and ventricular arrhythmias in animal models. OBJECTIVE: To determine whether SCS reduces the susceptibility to atrial fibrillation (AF) induced by tachypacing (TP). METHODS: In 21 canines, upper thoracic SCS systems and custom cardiac pacing systems were implanted. Right atrial and left atrial effective refractory periods were measured at baseline and after 15 minutes of SCS. Following recovery in a subset of canines, pacemakers were turned on to induce AF by alternately delivering TP and searching for AF. Canines were randomized to no SCS therapy (CTL) or intermittent SCS therapy on the initiation of TP (EARLY) or after 8 weeks of TP (LATE). AF burden (percent AF relative to total sense time) and AF inducibility (percentage of TP periods resulting in AF) were monitored weekly. After 15 weeks, echocardiography and histology were performed. RESULTS: Effective refractory periods increased by 21 ± 14 ms (P = .001) in the left atrium and 29 ± 12 ms (P = .002) in the right atrium after acute SCS. AF burden was reduced for 11 weeks in EARLY compared with CTL (P <.05) animals. AF inducibility remained lower by week 15 in EARLY compared with CTL animals (32% ± 10% vs 91% ± 6%; P <.05). AF burden and inducibility were not significantly different between LATE and CTL animals. There were no structural differences among any groups. CONCLUSIONS: SCS prolonged atrial effective refractory periods and reduced AF burden and inducibility in a canine AF model induced by TP. These data suggest that SCS may represent a treatment option for AF.

Spatiotemporal electrophysiological changes in a murine ablation model.

AIMS: High recurrence rates after complex radiofrequency ablation procedures, such as for atrial fibrillation, remain a major clinical problem. Local electrophysiological changes that occur following cardiac ablation therapy are incompletely described in the literature. The purpose of this study was to determine whether alterations in conduction velocity, action potential duration (APD), and effective refractory period resolve dynamically following cardiac ablation. METHODS AND RESULTS: Lesions were delivered to the right ventricle of mice using a subxiphoid approach. The sham-operated control group (SHAM) received the same procedure without energy delivery. Hearts were isolated at 0, 1, 7, 30, and 60 days following the procedure and electrophysiological parameters were obtained using high-resolution optical mapping with a voltage-sensitive dye. Conduction velocity was significantly decreased at the lesion border in the 0, 7, and 30 day groups compared to SHAM. APD(70) at the lesion border was significantly increased at all time points compared to SHAM. Effective refractory period was significantly increased at the lesion border at 0, 1, 7, and 30 days but not at 60 days post-ablation. This study demonstrated that post-ablation electrophysiological changes take place immediately following energy delivery and resolve within 60 days. CONCLUSIONS: Cardiac ablation causes significant electrophysiological changes both within the lesion and beyond the border zone. Late recovery of electrical conduction in individual lesions is consistent with clinical data demonstrating that arrhythmia recurrence is associated with failure to maintain bi-directional conduction block.

Notch signaling regulates murine atrioventricular conduction and the formation of accessory pathways.

Ventricular preexcitation, which characterizes Wolff-Parkinson-White syndrome, is caused by the presence of accessory pathways that can rapidly conduct electrical impulses from atria to ventricles, without the intrinsic delay characteristic of the atrioventricular (AV) node. Preexcitation is associated with an increased risk of tachyarrhythmia, palpitations, syncope, and sudden death. Although the pathology and electrophysiology of preexcitation syndromes are well characterized, the developmental mechanisms are poorly understood, and few animal models that faithfully recapitulate the human disorder have been described. Here we show that activation of Notch signaling in the developing myocardium of mice can produce fully penetrant accessory pathways and ventricular preexcitation. Conversely, inhibition of Notch signaling in the developing myocardium resulted in a hypoplastic AV node, with specific loss of slow-conducting cells expressing connexin-30.2 (Cx30.2) and a resulting loss of physiologic AV conduction delay. Taken together, our results suggest that Notch regulates the functional maturation of AV canal embryonic myocardium during the development of the specialized conduction system. Our results also show that ventricular preexcitation can arise from inappropriate patterning of the AV canal-derived myocardium.