Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5

Mechanisms of ventricular arrhythmias in a Langendorff model of early repolarization
J. Wolfes1, C. Ellermann1, L. Kirchner1, K. Willy1, P. Leitz1, B. Rath1, L. Eckardt1, G. Frommeyer1
1Klinik für Kardiologie II - Rhythmologie, Universitätsklinikum Münster, Münster;

Background: 

Given the complexity and clinical relevance of J wave syndromes and early repolarization the understanding of electrophysiological mechanisms leading to ventricular arrhythmias is rather sparse. This study aimed at introducing a Langendorff rabbit whole-heart model with pharmacological provoked early repolarization to achieve a deeper understanding of ventricular arrhythmias resulting from early repolarization syndrome (ERS).

 

Methods and results: 10 hearts of female New Zealand White rabbits were excised and retrogradely perfused employing a Langendorff-setup. To achieve the electrophysiological patterns of ERS, a perfusion with the KV4.2- and KV4.3-channel activator NS5806 in combination with verapamil and the ATP-dependent potassium channel opener pinacidil were administered. 5 MAP-catheters were placed on the AV-blocked hearts with two catheters on the endocardial side of LV- and RV-outflow-tract and two catheters on the opposing epicardial side of LV- and RV-outflow-tract. One catheter was placed on the apical ventricular septum. An electrophysiology study was performed to obtain the electrophysiological parameters (EP) including action potential duration (APD), effective refractory period (ERP), and arrhythmia inducibility by programmed ventricular stimulation on the endocardial and epicardial side of the opposing myocardium. After determination of EP under baseline conditions the hearts were perfused with 7µM NS5806 and 3µM Verapamil and EP were redetermined. Afterwards, the hearts were perfused with 7µM NS5806 and 5µM pinacidil and the EP were measured again. Perfusion with both combinations resulted in a significant APD and ERP shortening, whereas epicardial ERP was significantly more shortened than endocardial ERP. Simultaneously, the arrhythmia inducibility by programmed ventricular stimulation was significantly raised by both perfusions. Notably, programmed epicardial ventricular stimulation resulted in significantly more VT episodes than programmed ventricular stimulation from the opposing endocardium.

 

Conclusion:

Pharmacological stimulation with NS5806 and Verapamil or Pinacidil resulted in significant APD and ERP shortening, whereat endo- to epicardial ERP dispersion might be a key mechanism for raised arrhythmia susceptibility with significantly raised epicardial arrhythmia inducibility. 

  

https://dgk.org/kongress_programme/jt2022/aV1395.html