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). 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 electrophysiological 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. 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, resulting in blood carboxyhaemoglobin levels comparable to those found in human smokers. Methods: Action potential and ionic currents were measured in patch-clamped myocytes isolated at different ages after birth (1, 2, 4 and 8 weeks). Cells were superfused with a normal Tyrode's solution (to measure action potential, AP) or appropriately modified Tyrode's solutions (to measure transient outward current, TO and the L-type calcium current, CaL). Results: Postnatal increase in cell size was similar in both groups; however, differences were observed in the electrophysiological parameters during growth. APD measured at -50 mV (APD50) progressively decreased in CTR from 131±24 ms at 1 week (n=14) to 78±8 ms at 4 weeks (n=14) and 67±7 ms at 8 weeks (n=10). This process was delayed in CO: at 4 weeks, APD50 remained significantly prolonged (148±24 ms, n=13) versus 4-week old CTR (p<0.02) and progressively shortened up to 92±12 ms (n=10) at 8 weeks. The ionic basis of APD shortening involved both calcium and potassium currents abnormalities. At 4 weeks, the density of CaL was significantly (p<0.02) higher in CO than in CTR (21±2 pA/pF, n=17, vs. 16±2 pA/pF, n=22) and normalized thereafter (at 8 weeks: 15±1 pA/pF, n=28 in CTR and 14±1 pA/pF, n=18 in CO). TO density progressively increased in CTR (in pA/pF, from 4±1 at 1 week to 13±2 at 4 weeks and 14±2 at 8 weeks, p<0.01), but it remained lower in CO at 4 and 8 weeks (respectively, 7±1 pA/pF, n=22, p<0.01 vs. 4-week old CTR; 8.5 pA/pF, n=13, p<0.01 vs. 8-week old CTR). Conclusions: Prenatal CO exposure affects the physiological shortening of APD, thus favoring QT prolongation and related arrhythmias and possibly contributing to SIDS occurrence.
|Titolo:||Prenatal exposure to carbon monoxide delays post-natal electrophysiologic maturation of rat ventricular myocytes|
|Anno di registrazione:||2002|
|Autori di Ateneo:|
|Autori:||L Sartiani; G. Lonardo; P. De Paoli; R. Cagiano; V. Cuomo ; E. Cerbai; A. Mugelli|
|Appare nelle tipologie:||1c - Abstract su rivista|
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