In-utero Exposure to Nicotine Alters the Response of the Cardiac Sodium Current to Isoproterenol; a Potential Mechanism for Sudden Infant Death Syndrome - Abstract
Rationale: In-utero exposure to tobacco smoke is strongly associated to sudden infant death syndrome (SIDS) with cardiac arrhythmias considered the final cause of death. The mechanisms causing these arrhythmias remain largely unknown but seem to be linked to conduction anomalies and the inability of the newborn to accelerate cardiac rhythm at the onset of apnea.
Objectives: We previously reported that in-utero exposure to nicotine delays the development of the heart sinoatrial node and reduce its innervation for several weeks after birth in rabbits. Our goal with this study is to determine if exposing rabbit fetus to nicotine also altered the sodium current (INa) response to adrenergic stimulus in newborn kittens. Our general hypothesis is that a loss of adrenergic response prevents heart acceleration and awakening of newborn
during sleep apnea.
Methods and results: Using electrophysiological techniques (patch clamp) on isolated cardiomyocytes we found that ?-adrenoreceptor agonist
isoproterenol increases the amplitude of INa by 50% in sham rabbits but had no effects in kittens exposed to nicotine in-utero. Analysis of the data also
showed that nicotine abolished the increase in late sodium current by isoproterenol, an effect that will reduce the ability of newborn to increase their heart
rate and may promote bradycardia. These results may in part explain the lack of arousal from sleep apnea in nicotine exposed infants and suggest that other
arrhythmogenic mechanisms may also contribute to SIDS.
Conclusion: Our study provides the first evidence that nicotine may precipitate SIDS by altering the adrenergic response of the heart. This represents a
new paradigm based on remodeling the cardiac electrical system as opposed to the current dogma of a centrally mediated respiratory deficit. The data also
raise awareness on the use of nicotine replacement therapies for pregnant women.