Spontaneous and inducible ventricular arrhythmias after myocardial infarction in mice.
BACKGROUND
Remodeling of gap junctions has been implicated in development of ventricular arrhythmias following myocardial infarction (MI) but the specific contribution of reduced electrical coupling is not known. We addressed this question using hearts from mice heterozygous for a connexin43 null allele (Cx43(+/-)).


METHODS
To determine whether Cx43-deficient mice exhibit increased spontaneous ventricular arrhythmias in the setting of chronic ischemic heart disease, radiofrequency transmitters were implanted in wild-type and Cx43(+/-) mice 2 days or 9 weeks after left anterior descending coronary artery ligation or sham operations. ECGs were recorded from unanesthetized, unrestrained mice 1 and 10 weeks after MI. Isolated, perfused hearts excised 1 and 10 weeks after MI were subjected to programmed electrical stimulation to induce arrhythmias.


CONCLUSIONS
Hearts with infarcts exhibited more spontaneous and inducible arrhythmias, but there was no significant difference between wild-type and Cx43-deficient mice. Fewer hearts exhibited spontaneous ventricular tachycardia (VT) in vivo than were inducible in vitro, suggesting that structural and functional substrates for inducible VT in isolated hearts may not be sufficient for initiation and maintenance of sustained VT in vivo. Previous studies have shown that Cx43-deficient mice exhibit more VT than wild-type mice during acute regional ischemia. Mice with MI exhibit increased arrhythmias. However, reduced coupling in Cx43-deficient mice does not significantly enhance spontaneous or inducible VT after MI.
Betsuyaku
Tetsuo
T
Department of Medicine (Cardiovascular Division), Washington University School of Medicine, St. Louis, MO 63110, USA.
Kanno
Shigeto
S
Lerner
Deborah L
DL
Schuessler
Richard B
RB
Saffitz
Jeffrey E
JE
Yamada
Kathryn A
KA
D000818:Animals; D018031:Connexin 43 / Q000172:deficiency* / Q000235:genetics; D004558:Electric Stimulation; D004562:Electrocardiography; D017629:Gap Junctions / Q000502:physiology; D051379:Mice; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology*; D009924:Organ Culture Techniques; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000503:physiopathology*
D018031:Connexin 43