Molecular and ionic basis of congenital complete heart block

Congenital heart? block (CHB), detected at or before birth in a structurall y normal heart, is strongly associated with autoantibodies reactive with th e intracellular soluble ribonucleoproteins 48kD SSB/La, 52kD SSA/Ro, and 60 kD SSA/Ro, CHB is presumed to be due to the transplacental passage of autoa ntibodies front the mother into the fetal circulation, Varying degrees of h eart block have been reported. Although second degree block has, on rave oc casion, reverted to normal sinus rhythm, complete atrio-ventricular (AV) bl ock is irreversible. CHB carr-ies substantial mortality and morbidity, with >60% of affected children requiring lifelong pacemakers. The recurrence I- ate exceeds, by at least twofold, that of the fit-st birth and is likely to influence the decision to have more children. Curiously the mother's heart is almost never affected (with complete heart block) despite exposure to i dentical circulating autoantibodies. As part of our continuing effort to un derstand the complex factors contributing to the pathogenesis of CHB, we ha ve established an animal model of CHB by immunizing female mice with recomb inant proteins/antigens, reproduced the human complete AV block in an isola ted Langendorff perfused fetal heart, and correlated these findings with L- type Ca channel inhibition bq, maternal antibodies front mothers of childre n with CHB. In addition, we established a passive animal model by directly injecting maternal antibodies into pregnant mice and reported significant s inus bradycardia, indicating that the spectrum of conduction abnormalities may extend beyond the AV node. All together, the data provided strong evide nce supporting an etiologic role of antibody/Ca channel involvement in the pathogenesis of CHB. However; other vet unknown factors seem necessary, to explain the full expression of CHB, (C) 2001, Elsevier Science Inc.