Electrophysiological abnormalities and arrhythmias in alpha MHC mutant familial hypertrophic cardiomyopathy mice.
A new mouse cardiac electrophysiology method was used to study mice harboring an alpha-myosin heavy chain Arg403Gln missense mutation (alpha-MHC403/+), which results in histological and hemodynamic abnormalities characteristic of familial hypertrophic cardiomyopathy (FHC) and sudden death of uncertain etiology during exercise. Wild-type animals had completely normal cardiac electrophysiology. In contrast, FHC mice demonstrated (a) electrocardiographic abnormalities including prolonged repolarization intervals and rightward axis; (b) electrophysiological abnormalities including heterogeneous ventricular conduction properties and prolonged sinus node recovery time; and (c) inducible ventricular ectopy. These data identify distinct electrophysiologic abnormalities in FHC mice with a specific alpha-myosin mutation, and also validate a novel method to explore in vivo the relationship between specific genotypes and their electrophysiologic phenotypes.
Berul
C I
CI
Division of Pediatric Cardiology, Tufts University School of Medicine, Massachusetts 02111, USA. charles.berul@es.nemc.org
Christe
M E
ME
Aronovitz
M J
MJ
Seidman
C E
CE
Seidman
J G
JG
Mendelsohn
M E
ME
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000503:physiopathology*; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004594:Electrophysiology / Q000379:methods; D006329:Heart Conduction System / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D018995:Myosin Heavy Chains / Q000235:genetics*; D011446:Prospective Studies
D018995:Myosin Heavy Chains