title: Implications of ventricular arrhythmia vulnerability during murine electrophysiology studies.
abstract: Programmed ventricular stimulation is being performed for the provocation of ventricular arrhythmias in genetically engineered mice. Despite the high level of interest in this area of translational research, little attention has been given to differentiating between selectivity and specificity of induced ventricular tachycardia (VT) in phenotypically normal mice. We aimed to assess factors that may enhance inducibility of VT in wild-type (WT) mice. In vivo intracardiac electrophysiological studies (EPS) were performed in 230 WT mice of 4 strains. An octapolar electrode catheter was inserted into a jugular vein and advanced to the right atrium and ventricle. Baseline ventricular conduction, refractoriness, and arrhythmia inducibility were assessed using programmed electrical stimulation (PES) and burst pacing. We found that nonsustained VT (> or =4 beats) was inducible in 68/230 (30%) mice. Duration of VT was 1.6 +/- 2.4 s, and the longest episode lasted 24 s. VT inducibility differed by strain and age. Ventricular effective refractory period (VERP) was shorter in mice with inducible VT (44 +/- 12 ms) compared with noninducible mice (61 +/- 16 ms, P < 0.001). VERP increased with age (P < 0.001), albeit with strain-related variability. We conclude that nonsustained VT in WT mice is reproducibly inducible and common. Genetic background variability may predispose certain strains to a higher incidence of arrhythmia induction. EPS methods impact prevalence and specificity of inducible VT. Increased VT inducibility was seen with shorter coupling intervals and application of tightly coupled extrastimuli techniques. These factors should be carefully considered when analyzing PES and burst pacing data in murine models to minimize false positives and optimize accuracy.
authors.affiliation: Department of Cardiology, Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Colin T
authors.initials: CT
authors.lastname: Maguire
authors.forename: Hiroko
authors.initials: H
authors.lastname: Wakimoto
authors.forename: Vickas V
authors.initials: VV
authors.lastname: Patel
authors.forename: Peter E
authors.initials: PE
authors.lastname: Hammer
authors.forename: Kimberlee
authors.initials: K
authors.lastname: Gauvreau
authors.forename: Charles I
authors.initials: CI
authors.lastname: Berul
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004558:Electric Stimulation; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012737:Sex Factors; D017180:Tachycardia, Ventricular / Q000209:etiology*