Published Online
on January 12, 2004

A more recent version of this article appeared on January 27, 2004

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Submitted on April 8, 2003
Revised on August 12, 2003
Accepted on September 22, 2003

Prenatal Exposure to Carbon Monoxide Affects Postnatal Cellular Electrophysiological Maturation of the Rat Heart. A Potential Substrate for Arrhythmogenesis in Infancy

Laura Sartiani PhD, Elisabetta Cerbai PhD, Giuseppe Lonardo BiolD, Petra DePaoli PharmD, Maria Tattoli MD, Raffaele Cagiano PhD, Maria Rosaria Carratù MD, Vincenzo Cuomo MD, and Alessandro Mugelli MD^*

From the Department of Preclinical and Clinical Pharmacology, University of Florence, Florence (L.S., E.C., G.L., P.D., A.M.); the Department of Pharmacology, University of Bari, Bari (M.T., R.C., M.R.C.); and the Department of Pharmacology and General Physiology, University La Sapienza, Rome (V.C.), Italy.

^* To whom correspondence should be addressed. E-mail: alessandro.mugelli{at}unifi.it.

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.

Methods and 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.

Key words: death, sudden, infant • electrophysiology • ion channels • smoking • carbon monoxide

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