Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada.
Montreal Heart Institute, University of Montreal, Montréal, Quebec, Canada.
Heart Rhythm. 2019 Apr;16(4):494-501. doi: 10.1016/j.hrthm.2019.02.013.
In utero exposure to tobacco smoke is associated with sudden infant death syndrome (SIDS) and cardiac arrhythmias in newborns. The arrhythmogenic mechanisms seem linked to alterations of the cardiac sodium current (I). We previously reported that in utero exposure to nicotine delays the postnatal development of the heart sinoatrial node in rabbits and altered expression of the sodium channels Na1.5 and Na1.1 in the atrium surrounding it. These channels react differently to sympathetic stimulation.
The purpose of this study was to test whether nicotine altered the response of I to stimulation by the β-adrenoreceptor agonist isoproterenol in atrial myocytes. Our hypothesis is that changes in the sympathetic response of sinoatrial node peripheral cells may create a substrate for arrhythmia.
Using the patch-clamp technique we measured the effect of nicotine on the response of I to adrenergic stimulation in isolated cardiomyocytes.
Isoproterenol increased I by 50% in newborn sham rabbits but had no effect in newborn rabbits exposed to nicotine in utero. Our data also show that nicotine increases the late sodium current, an effect that may promote QT prolongation.
We provide the first evidence linking fetal exposure to nicotine to long-term alterations of I response to isoproterenol. These changes may impair I adaptation to sympathetic tone and prevent awakening from sleep apnea, thus leading to arrhythmias that could potentially be involved in SIDS. Our data also raise concerns about the use of nicotine replacement therapies for pregnant women.
子宫内暴露于烟草烟雾与新生儿猝死综合征（SIDS）和心律失常有关。心律失常的机制似乎与心脏钠离子电流（I）的改变有关。我们之前的报告表明，子宫内暴露于尼古丁会延迟兔子心脏窦房结的产后发育，并改变其周围心房的钠离子通道 Na1.5 和 Na1.1 的表达。这些通道对交感神经刺激的反应不同。
本研究旨在测试尼古丁是否改变了 I 对β-肾上腺素能激动剂异丙肾上腺素刺激的反应。我们的假设是，窦房结周围细胞交感神经反应的变化可能为心律失常创造一个基质。
使用膜片钳技术，我们测量了尼古丁对分离的心肌细胞中 I 对肾上腺素刺激反应的影响。
异丙肾上腺素使新生假兔的 I 增加了 50%，但对子宫内暴露于尼古丁的新生兔没有影响。我们的数据还表明，尼古丁增加了晚期钠离子电流，这一效应可能会导致 QT 延长。
我们首次提供了将胎儿暴露于尼古丁与 I 对异丙肾上腺素反应的长期改变联系起来的证据。这些变化可能会损害 I 对交感神经张力的适应能力，并防止从睡眠呼吸暂停中醒来，从而导致心律失常，这可能与 SIDS 有关。我们的数据还引起了对孕妇使用尼古丁替代疗法的关注。
