Congenital heart? block (CHB), detected at or before birth in a structurally normal heart, is strongly associated with autoantibodies reactive with the intracellular soluble ribonucleoproteins 48kD SSB/La, 52kD SSA/Ro, and 60kD SSA/Ro, CHB is presumed to be due to the transplacental passage of autoantibodies front the mother into the fetal circulation, Varying degrees of heart block have been reported. Although second degree block has, on rave occasion, reverted to normal sinus rhythm, complete atrio-ventricular (AV) block 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 identical circulating autoantibodies. As part of our continuing effort to understand the complex factors contributing to the pathogenesis of CHB, we have established an animal model of CHB by immunizing female mice with recombinant proteins/antigens, reproduced the human complete AV block in an isolated Langendorff perfused fetal heart, and correlated these findings with L-type Ca channel inhibition bq, maternal antibodies front mothers of children with CHB. In addition, we established a passive animal model by directly injecting maternal antibodies into pregnant mice and reported significant sinus bradycardia, indicating that the spectrum of conduction abnormalities may extend beyond the AV node. All together, the data provided strong evidence 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.
