Abstract
Genetically-manipulated mice harboring an α-myosin heavy chain Arg403Gln missense mutation (α-MHC 403/+ ) display a phenotype characteristic of familial hypertrophic cardiomyopathy (FHC). Male and female (30±8 week old) heterozygous α-MHC 403/+ mice and littermate controls were evaluated using a surface electrocardiogram (ECG) and an in vivo cardiac electrophysiology study (EPS). Wild type animals had normal intracardiac electrophysiology, with no significant differences between male and female control mice during EPS. The female wild-type mice did have slower heart rates and longer ECG intervals than their male wild-type counterparts. The female α-MHC 403/+ mice had similar ECG's, cardiac conduction times, and refractory periods compared with female wild-type mice. In contrast, male FHC mice had distinctive ECG and electrophysiologic abnormalities including right axis deviation, prolonged ventricular repolarization and prolonged sinus node recovery times. During programmed ventricular stimulation, 62% of male α-MHC 403/+ mice and 28% of female α-MHC 403/+ mice had inducible ventricular tachycardia. These studies identify gender-specific electrophysiologic abnormalities in α-MHC 403/+ FHC mice, concordant with the histological and hemodynamic derangements previously reported.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Seidman CE, Seidman JG. Gene mutations that cause familial hypertrophic cardiomyopathy. In: Haber E, ed. Molecular Cardiovascular Medicine. New York: Scientific American Press, 1995;193–210.
Watkins H, McKenna W, Thierfelder L, Suk HJ, Anan R, O'Donoghue A, Spirito P, Matsumori A, Moravec CS, Seidman JG, Seidman CE. Mutations in the genes for cardiac troponin T and a-tropomyosin in hypertrophic cardiomyopathy. N Engl J Med1995;332:1058–1064.
Geisterfer-Lowrancen AAT, Christe ME, Conner D, Ingwall J, Schoen F, Seidman CE, Seidman JG. A mouse model of familial hypertrophic cardiomyopathy. Science 1996;272: 732–734.
Berul CI, Aronovitz MJ, Wang PJ, Mendelsohn ME. In vivo cardiac electrophysiology studies in the mouse. Circulation 1996;94:2641–2648.
Berul CI, Christe ME, Aronovitz MJ, Seidman CE, Seidman JG, Mendelsohn ME. Electrophysiological abnormalities and arrhythmias in a-MHC mutant familial hypertrophic cardiomyopathy mice. J Clin Invest 1997;99:274–280.
Bazett HC. An analysis of the time relationships of the heart. Heart 1920;7:353–370.
Berul CI, Sweeten TL, Dubin AM, Shah MJ, Vetter VL. Use of the rate-corrected JT interval for prediction of repolarization abnormalities in children. Am J Cardiol 1994;74: 1254–1257.
Gillette PC, Buckles DC, Harold H, Garson A. Intracardiac electrophysiology studies. In: Gillette PC, Garson A, eds. Pediatric Arrhythmias: Electrophysiology and Pacing. Philadelphia: WB Saunders, 1990;216–248.
Roberts NK, Gillette PC. Electrophysiologic study of the conduction system in normal children. Pediatrics 1997;60: 868–863.
Kugler JD. Electrophysiology studies. In: Emmanouilides GC, Reimenschneider TA, Allen HD, Gutgesell HP, eds. Moss and Adams' Heart Disease in Infants, Children, and Adolescents, including the Fetus and Young Adult. Baltimore: Williams & Wilkins, 1995;347–366.
Mandel W, Hayakawa H, Danzig R, Marcus HS. Evaluation of sino-atrial node function in man by overdrive suppression. Circulation 1971;44:59–66.
Zipes DP. Specific arrhythmias: diagnosis and treatment. In: Braunwald E, ed. Heart disease: A Textbook of Car-diovascular Medicine. Philadelphia: WB Saunders, 1992; 667–725.
Vetter VL. The pediatric electrophysiology study. In: Leibman J, Plonsey R, Rudy Y, eds. Pediatric and Fundamental Electrocardiography. New York: Martinus Nijhoff, 1985; 161–184.
Fananapazir L, Chang AC, Epstein SE, McAreavy D. Prognostic determinants in hypertrophic cardiomyopathy: prospective evaluation of a therapeutic strategy based on clinical, Holter, hemodynamic, and electrophysiological findings. Circulation 1992;86:730–740.
Epstein ND, _Cohn GM, Cyran F, Fananapazir L. Differences in clinical expression of hypertrophic cardiomyopathy associated with two distinct mutations in a-myosin heavy chain gene. Circulation 1992;86:345–352.
Buja G, Miorelli M, Turrini P, Melacini P, Nava A. Comparison of QT dispersion in hypertrophic cardiomyopathy between patients with and without ventricular arrhythmias and sudden death. Am J Cardiol 1993; 72:973–976.
Wigle ED, Rakowski H, Kimball BP, Williams WG. Hypertrophic cardiomyopathy: clinical spectrum and treatment. Circulation 1995; 92:1680–1692.
Fananapazir L, Epstein SE. Hemodynamic and electrophysiologic evaluation of patients with hypertrophic cardiomyopathy surviving cardiac arrest. Am J Cardiol 1991; 67:280–287.
Maron BJ, Fananapazir L. Sudden cardiac death in hypertrophic cardiomyopathy. Circulation 1992; 85:I57–63.
Watson RM, Schwartz JL, Maron BJ, Tucker E, Rosing DR, Josephson ME. Inducible polymorphic ventricular tachycardia and ventricular fibrillation in a subgroup of patients with hypertrophic cardiomyopathy at risk for sudden death. J Am Coll Cardiol 1987; 10:761–774.
Scheidt S. Basic electrocardiography: abnormalities of electrocardiographic patterns. Clinical Symposia 1984; 36:2–32.
Karas RH, Baur WE, Mendelsohn ME. Human vascular smooth muscle cells express a novel estrogen receptor isoform. Circulation 1994; 90:462–469.
Sullivan TR Jr, Karas RH, Aronovitz M, Faller GT, Ziar JP, Smith JJ, O'Donnell TF Jr, Mendelsohn E. Estrogen inhibits the response-to-injury in a mouse carotid artery model. J Clin Invest 1995; 96:2482–2488.
Iafrati MD, Karas RH, Aronovitz M, Kim S, Sullivan TR Jr, Lubhan DB, O'Donnell TF Jr, Korach KS, Mendelson ME. Estrogen inhibits the vascular injury response in estrogen receptor a-deficient mice. Nature Medicine 1997; 3:545–548.
Jiang C, Poole-Wilson PA, Sarrel PM, Mochizuki S, Collins P, MacLeod KT. Effect of 17-beta-oestradiol on contraction, Ca+2 current and intracellular free Ca+2 in guinea-pig isolated cardiac myocytes. Br J Pharmacol 1982; 106:739–745.
Weiner CP, Lizasoain I, Baylis SA, Knowles RG, Charles IG, Moncada S. Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci USA 1994; 91:5212–5216.
Mershon JI, Mikala G, Schwartz A. Changes in expression of the L-type voltage-dependent calcium channel during pregnancy and parturition in the rat. Biol Reproduction 1994; 51:993–999.
Nakajima T, Kitazawa T, Hamada E, Omata M, Kurachi Y. 17B-estradiol inhibits the voltage-dependent L-type Ca2+currents in aortic smooth muscle cells. Eur J Pharmacol 1995; 294:625–635. 1995.
Watkins H, Rosenweig A, Hwang D, Levi T, McKenna W, Seidman CE, Seidman JG. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med 1992; 326:1108–1114.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Berul, C.I., Christe, M.E., Aronovitz, M.J. et al. Familial Hypertrophic Cardiomyopathy Mice Display Gender Differences in Electrophysiological Abnormalities. J Interv Card Electrophysiol 2, 7–14 (1997). https://doi.org/10.1023/A:1009700404218
Issue Date:
DOI: https://doi.org/10.1023/A:1009700404218