Electrocardiographic abnormalities in a murine model injected with IgG from mothers of children with congenital heart block

Background-It is a widely held view that congenital heart block (CHB) is ca used by the transplacental transfer of maternal autoantibodies (anti-SSA/Ro and/or anti-SSB/La) into the fetal circulation. To test this hypothesis an d to reproduce human CHB, an experimental mouse model (BALB/c) was develope d by passive transfer of human autoantibodies into pregnant mice. Methods and Results-Timed pregnant mice (n=54) were injected with a single intravenous bolus of purified IgG containing human anti-SSA/Ro and anti-SSB /La antibodies from mothers of children with CHB. To parallel the "window p eriod" of susceptibility to CHB in humans, 3 groups of mice were used: 8, 1 1, and 16 days of gestation. Within each group, we tested 10, 25, 50, and 1 00 mu g of IgG. At delivery, ECGs were recorded and analyzed for conduction abnormalities. Bradycardia and PR interval were significantly increased in 8-, 11-, and 16-day gestational groups when compared with controls (P<0.05 ). QRS duration was not significantly different between all groups. Antibod y levels measured by ELISA in both mothers and their offspring confirmed th e transplacental transfer of the human antibodies to the pups. Conclusions-The passive transfer model demonstrated bradycardia, first-degr ee but not complete atrioventricular block in pups. The greater percentage and degree of bradycardia and PR prolongation in the ii-day mouse group cor relates with the "window period" of susceptibility observed in humans. The high incidence of bradycardia suggests possible sinoatrial node involvement . All together, these data provide relevant insights into the pathogenesis of CHB.