Ventricular arrhythmia vulnerability in cardiomyopathic mice with homozygous mutant myosin-binding protein C gene

• Published in: Circulation (New York, N.Y.) N.Y.), 2001-11, Vol.104 (22), p.2734-2739
• Main Authors: BERUL, Charles I, MCCONNELL, Bradley K, WAKIMOTO, Hiroko, MOSKOWITZ, Ivan P. G, MAGUIRE, Colin T, SEMSARIAN, Christopher, VARGAS, Marcel M, GEHRMANN, Josef, SEIDMAN, Christine E, SEIDMAN, Jonathan G
• Format: Article
• Language: English
• Subjects: Animals; Arrhythmias, Cardiac - complications; Arrhythmias, Cardiac - genetics; Arrhythmias, Cardiac - physiopathology; Biological and medical sciences; Cardiology. Vascular system; Cardiomyopathies - complications; Cardiomyopathies - genetics; Cardiomyopathies - pathology; Cardiomyopathies - physiopathology; Carrier Proteins - genetics; Disease Models, Animal; Electrocardiography; Electrophysiologic Techniques, Cardiac; Genetic Predisposition to Disease; Heart; Heart Conduction System - physiopathology; Heart Rate; Heart Ventricles - physiopathology; Heterozygote; Homozygote; Male; Medical sciences; Mice; Mice, Mutant Strains; Mutation; Myocarditis. Cardiomyopathies; Myocardium - pathology; Phenotype; Sequence Deletion
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/hc4701.099582

Homozygous mutant mice expressing a truncated form of myosin-binding protein C (MyBP-C(t/t)) develop severe dilated cardiomyopathy, whereas the heterozygous mutation (MyBP-C(t/+)) causes mild hypertrophic cardiomyopathy. Adult male MyBP-C(t/t) and MyBP-C(t/+) mice were evaluated for arrhythmia vulnerability with an in vivo electrophysiology study. Surface ECGs were obtained for heart rate, rhythm, and conduction intervals. Atrial, atrioventricular, and ventricular conduction parameters and refractoriness were assessed in 22 MyBP-C(t/t), 10 MyBP-C(t/+), and 17 wild-type MyBP-C(+/+) mice with endocardial pacing and intracardiac electrogram recording. Arrhythmia induction was attempted with standardized programmed stimulation at baseline and with isoproterenol. Heart rate variability and ambient arrhythmia activity were assessed with telemetric ECG monitors. Quantitative histological characterization was performed on serial sections of excised hearts. MyBP-C(t/t) and MyBP-C(t/+) mice have normal ECG intervals and sinus node, atrial, and ventricular conduction and refractoriness. Ventricular tachycardia was reproducibly inducible in 14 of 22 MyBP-C(t/t) mice (64%) during programmed stimulation, compared with 2 of 10 MyBP-C(t/+) mice (20%) and 0 of 17 wild-type controls (P