Abstract 15616: Nicotine delays the Development of Cardiac Conduction System: Potential Cause for Arrhythmias leading to Sudden Infant Death Syndrome
Introduction: More than 50% of newborns death is due to the sudden infant death syndrome (SIDS). Exposure to cigarette smoke represents the highest risk factor for SIDS. Cardiac bradycardias are observed in most cases of SIDS. The cardiac conduction system is molded by a resorptive degeneration process (apoptosis). Nicotine is known to possess anti-apoptotic effects. Therefore, we hypothesized that nicotine disrupts the maturation of the sinoatrial (SAN) and auriculoventricular (AVN) nodes, which in return can cause arrhythmias, leading to SIDS.
Methods: Osmotic pumps delivering nicotine were subcutaneously implanted in pregnant rabbits at their second week of pregnancy. We then characterized the level of apoptosis in SAN of newborn rabbits exposed or not to nicotine in utero. Moreover, we did immunofluorescence to localize the sodium channels (NaVs) within the SAN. Finally, using quantitative PCR, we quantified the expression of NaVs in the atria and ventricles of the newborn rabbits' hearts at 0, 7, 14 and 30 days postnatal.
Results: Nicotine decreased apoptosis at 7 days postnatal, thus preventing the early development of SAN. At 14 and 30 days when serum nicotine levels dropped to 0 ng/ml, apoptosis reached levels similar to unexposed rabbit hearts at 7 days. Nicotine inverted the expression pattern of SCN1A and SCN5A in the SAN of newborn rabbits at 0 day postnatal and increased the expression of SCN5A by 70 times in the right atrium at 30 days postnatal. Expression of SCN1A and SCN4A increased by 4 fold in the 0 day old treated rabbit in the atria and ventricles.
Conclusion: In conclusion, our study demonstrates that nicotine disturbed the resorptive degeneration process, delays the development of the SAN and regionally perturbed the expression of SCN1A, SCN4A and SCN5A. These changes can help explain the conduction disturbances observed in SIDS.
- © 2011 by American Heart Association, Inc.