Electrophysiologic characterization and postnatal development of ventricular pre-excitation in a mouse model of cardiac hypertrophy and Wolff-Parkinson-White syndrome.
J Am Coll Cardiol
; 42(5): 942-51, 2003 Sep 03.
Article
em En
| MEDLINE
| ID: mdl-12957447
ABSTRACT
OBJECTIVES:
We sought to characterize an animal model of the Wolff-Parkinson-White (WPW) syndrome to help elucidate the mechanisms of accessory pathway formation.BACKGROUND:
Patients with mutations in PRKAG2 manifest cardiac hypertrophy and ventricular pre-excitation; however, the mechanisms underlying the development and conduction of accessory pathways remain unknown.METHODS:
We created transgenic mice overexpressing either the Asn488Ile mutant (TG(N488I)) or wild-type (TG(WT)) human PRKAG2 complementary deoxyribonucleic acid under a cardiac-specific promoter. Both groups of transgenic mice underwent intracardiac electrophysiologic, electrocardiographic (ECG), and histologic analyses.RESULTS:
On the ECG, approximately 50% of TG(N488I) mice displayed sinus bradycardia and features suggestive of pre-excitation, not seen in TG(WT) mice. The electrophysiologic studies revealed a distinct atrioventricular (AV) connection apart from the AV node, using programmed stimulation. In TG(N488I) mice with pre-excitation, procainamide blocked bypass tract conduction, whereas adenosine infusion caused AV block in TG(WT) mice but not TG(N488I) mice with pre-excitation. Serial ECGs in 16 mice pups revealed no differences at birth. After one week, two of eight TG(N488I) pups had ECG features of pre-excitation, increasing to seven of eight pups by week 4. By nine weeks, one TG(N488I) mouse with WPW syndrome lost this phenotype, whereas TG(WT) pups never developed pre-excitation. Histologic investigation revealed postnatal development of myocardial connections through the annulus fibrosum of the AV valves in young TG(N488I) but not TG(WT) mice.CONCLUSIONS:
Transgenic mice overexpressing the Asn488Ile PRKAG2 mutation recapitulate an electrophysiologic phenotype similar to humans with this mutation. This includes procainamide-sensitive, adenosine-resistant accessory pathways induced in postnatal life that may rarely disappear later in life.
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Base de dados:
MEDLINE
Assunto principal:
Síndrome de Wolff-Parkinson-White
/
Síndromes de Pré-Excitação
/
Proteínas Serina-Treonina Quinases
/
Cardiomegalia
/
Disfunção Ventricular
/
Mutação de Sentido Incorreto
/
Modelos Animais de Doenças
/
Complexos Multienzimáticos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Am Coll Cardiol
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos