Nicotine Delays the Development of Cardiac Conduction System: Leading to Sudden Infant Death Syndrome

Abstract

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. 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.Osmotic pumps delivering nicotine were implanted in rabbits at their second week of pregnancy. We characterized the level of apoptosis in SAN of newborn rabbits exposed or not to nicotine. Moreover, we did patch clamp techniques to evaluate the effects of nicotine on adrenergic responses. Finally, using quantitative PCR, we quantified the expression of sodium channels in the atria of the rabbits’ hearts at 0, 7, 14 and 30 days postnatal.Nicotine decreased apoptosis at 7 days postnatal, thus preventing the early development of SAN. At 14 and 30 days when serum nicotine levels reached 0 ng/ml, apoptosis reached levels similar to unexposed rabbit at 7 days. Nicotine inverted the expression pattern of SCN1A and SCN5A in the SAN of 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. Finally, nicotine suppresses the effect of isoproterenol on sodium channels.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 might explain the conduction disturbances observed in SIDS.