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Optical mapping of activation patterns in an animal model of congenital heart block
M Restivo1, D O Kozhevnikov, M Boutjdir
1Molecular and Cellular Cardiology Program, Veterans Affairs New York Harbor Health Care System, Brooklyn, New York 11209, USA. mrestivo@bigfoot.com
Insights
Maternal autoantibodies linked to congenital heart block (CHB) also cause sinus bradycardia in developing hearts. This suggests impaired sinoatrial conduction may precede atrioventricular block in infants.
Area of Science:
- Cardiology
- Immunology
- Developmental Biology
Background:
- Congenital heart block (CHB) is a severe condition in infants, often linked to maternal autoantibodies.
- Maternal autoantibodies, specifically IgG targeting SSB/La and SSA/Ro ribonucleoproteins, are implicated in CHB pathogenesis.
Purpose of the Study:
- To investigate the direct effects of maternal IgG associated with CHB on cardiac electrical activation patterns.
- To determine if these maternal autoantibodies impact sinoatrial and atrioventricular conduction in a preclinical model.
Main Methods:
- Utilized Langendorff-perfused young rabbit hearts.
- Employed optical mapping with a 124-site photodiode array to record action potentials.
- Simultaneously imaged electrical activation in the right atrium (RA) and right ventricle (RV).
Main Results:
- Perfusion with positive IgG induced sinus bradycardia and varying degrees of heart block.
- Activation mapping showed significant conduction delay at the sinoatrial junction.
- No conduction disturbances were observed with IgG from mothers of healthy children.
Conclusions:
- Maternal IgG associated with CHB not only causes atrioventricular block but also sinus bradycardia.
- These findings indicate impaired intrasinus and/or sinoatrial conduction as a consequence of positive IgG.
- Sinus bradycardia in developing hearts may serve as an early indicator of potential atrioventricular conduction disturbances.
Abstract:
Congenital heart block (CHB) is associated with high mortality and affects children of mothers with autoantibodies (IgG) to ribonucleoproteins SSB/La and SSA/Ro. IgG from mothers of children with CHB (positive IgG) was used to assess activation patterns in both the right atrium (RA) and right ventricle (RV) of Langendorff-perfused young rabbit hearts. Optical action potentials (AP) were obtained by using a 124-site photodiode array with 4-[-[2-(di-n-butylamino)-6-naphthyl]vinyl]pyridinium. Optical APs were recorded to simultaneously image activation patterns from the RA and RV. Perfusion of positive IgG (800--1,200 micro resulted in sinus bradycardia and varying degrees of heart block. Activation maps revealed marked conduction delay at the sinoatrial junction but only minor changes in overall atrial and ventricular activation patterns. No conduction disturbances were seen in the presence of IgG from mothers with healthy children. In conclusion, besides atrioventricular (AV) block, positive IgG induces sinus bradycardia. These results establish that the sequelae of CHB are associated with impaired intrasinus and/or sinoatrial conduction. The findings raise the possibility that sinus bradycardia in the developing heart may indicate the potential for AV conduction disturbances.