Prenatal exposure to carbon monoxide alters the electrophysiologic maturation of neonatal rat ventricular myocytes: a link to sudden infant death syndrome?

Maternal smoking during pregnancy and prolongation of the QT interval on the electrocardiogram in the first weeks of life are considered as risk factors for Sudden Infant Death Syndrome (SIDS) (1). In animal models, prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, affects postnatal development of several organs; no data are available concerning cardiac development. In neonatal rat myocytes, the physiological cell growth is accompanied by a significant reduction of the action potential duration (APD), the cellular determinant of QT interval, due to an increased expression of the transient outward current, Ito (2). The aim of this study was to compare cell electrophysiological maturation in male Wistar rats born from mothers exposed to 0 (CTR) or 150 ppm CO during pregnancy. Action potential and ionic currents were measured in patch-clamped myocytes isolated at different ages after birth (1-5, 8-15, 20-30 days) (3). Postnatal increase in cell size was similar in both groups; however, differences were observed in the electrophysiologic parameters during growth. APD progressively decreased in CTR from 131±24 ms (n=14) to 76±13 ms (n=9) but not in CO, where it remained significantly prolonged (157±28 ms at 28 days, n=11, p<0.05 vs CTR). Ito density, which increased in CTR from 4.1±0.7 to 11.8±3.4 pA/pF (p<0.01), remained low in CO (5.8±0.9 pA/pF at 28 days, p<0.01 vs CTR). Thus, prenatal CO exposure affects the normal process of cardiac electrophysiological maturation, which may predispose to QT prolongation and related arrhythmias, thus contributing to SIDS occurrence.