This Article Full Text Full Text (PDF) All Versions of this Article: 109/3/419    most recent 01.CIR.0000109497.73223.4Dv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sartiani, L. Articles by Mugelli, A. Search for Related Content PubMed PubMed Citation Articles by Sartiani, L. Articles by Mugelli, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CARBON MONOXIDE Related Collections Electrophysiology Ion channels/membrane transport Cardiac development

(Circulation. 2004;109:419-423.)
© 2004 American Heart Association, Inc.

Basic Science Reports

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; 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.

Correspondence to Alessandro Mugelli, MD, Department of Preclinical and Clinical Pharmacology, Viale G. Pieraccini 6, 50139 Firenze, Italy. E-mail alessandro.mugelli{at}unifi.it

Received April 8, 2003; de novo received August 12, 2003; accepted September 22, 2003.

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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