Prenatal exposure to carbon monoxide affects postnatal cellular electrophysiological maturation of the rat heart: a potential substrate for arrhythmogenesis in infancy.
BACKGROUND
Maternal smoking is an independent risk factor for sudden infant death syndrome (SIDS). Carbon monoxide (CO) is a major component of smoke. No information is available about the effect of CO and/or smoking on postnatal maturation of the heart. The aim of this study was to investigate the effect of prenatal exposure to CO on cellular electrophysiological maturation in male Wistar rats.


RESULTS
The patch-clamp technique was used to measure action potential (AP) and ionic currents (I(to) and I(Ca,L)) from rat ventricular myocytes. During growth, AP duration measured at -20 and -50 mV (APD(-)(20) and APD(-)(50)) decreased progressively in both groups; the process was significantly delayed in rats exposed prenatally to 150 ppm CO: At 4 weeks, APD(-)(20) and APD(-)(50) were 89.5+/-18.2 and 147.7+/-24.5 ms in CO (n=13) and 35.6+/-4.5 and 77.8+/-8.3 ms in control rats (Ctr; n=14; P<0.01 and P<0.05, respectively) and normalized at 8 weeks. At 4 weeks, the density of I(Ca,L) was significantly higher (21.3+/-1.6 pA/pF, n=17, versus 15.9+/-1.6 pA/pF, n=22; P<0.05) and the density of I(to) significantly lower (9.6+/-1.5, n=22, versus 15.2+/-2.2 pA/pF, n=19; P<0.01) in CO than in Ctr and normalized thereafter.


CONCLUSIONS
Prenatal CO exposure affects the physiological shortening of APD in neonatal rats. We speculate that a prolonged myocyte repolarization induced by prenatal exposure to smoke may establish a period of vulnerability for life-threatening arrhythmias in infancy.
Sartiani
Laura
L
Department of Preclinical and Clinical Pharmacology, Viale G. Pieraccini 6, 50139 Firenze, Italy. alessandro.mugelli@unifi.it
Cerbai
Elisabetta
E
Lonardo
Giuseppe
G
DePaoli
Petra
P
Tattoli
Maria
M
Cagiano
Raffaele
R
Carratù
Maria Rosaria
MR
Cuomo
Vincenzo
V
Mugelli
Alessandro
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001145:Arrhythmias, Cardiac / Q000209:etiology; D015220:Calcium Channels / Q000378:metabolism; D002248:Carbon Monoxide / Q000494:pharmacology*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004553:Electric Conductivity; D005260:Female; D006321:Heart / Q000254:growth & development*; D008431:Maternal-Fetal Exchange; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D015220:Calcium Channels; D015221:Potassium Channels; D002248:Carbon Monoxide