A modified approach for programmed electrical stimulation in mice: Inducibility of ventricular arrhythmias

BACKGROUND: Electrophysiological studies in mice, the prevailing model organism in the field of basic cardiovascular research, are impeded by the low yield of programmed electrical stimulation (PES).

OBJECTIVE: To investigate a modified approach for ventricular arrhythmia (VA) induction and a novel scoring system in mice.

METHOD: A systematic review of literature on current methods for PES in mice searching the PubMed database revealed that VA inducibility was low and ranged widely (4.6 ± 10.7%). Based on this literature review, a modified PES protocol with 3 to 10 extrastimuli was developed and tested in comparison to the conventional PES protocol using up to 3 extrastimuli in anesthetized wildtype mice (C57BL/6J, n = 12). Induced VA, classified according to the Lambeth Convention, were assessed by established arrhythmia scores as well as a novel arrhythmia score based on VA duration.

RESULTS: PES with the modified approach raised both the occurrence and the duration of VA compared to conventional PES (0% vs 50%; novel VA score p = 0.0002). Particularly, coupling of >6 extrastimuli raised the induction of VA. Predominantly, premature ventricular complexes (n = 6) and ventricular tachycardia <1s (n = 4) were observed. Repeated PES after adrenergic stimulation using isoprenaline resulted in enhanced induction of ventricular tachycardia <1s in both protocols.

CONCLUSION: Our findings suggest that the presented approach of modified PES enables effective induction and quantification of VA in wildtype mice and may well be suited to document and evaluate detailed VA characteristics in mice.