In utero exposure to carbon monoxide alters the electrophysiological maturation of neonatal rat ventricular cardiomyocytes.

In vivo carbon monoxide (CO) exposure is a well-documented model of tissue hypoxia. Prenatal chronic exposure to low CO concentrations (150-200 ppm) produces various developmental alterations in the rat, including neurobehavioral modifications (Carratù et al., 1993) and changes in the electrical properties of rat skeletal muscle fibres (De Luca et al., 1996). These modifications suggest that prenatal exposure to CO may hinder postnatal development in rat. In neonatal rat hearts, the physiological cell growth is accompanied by a significant increase in the density of the transient outward current Ito, responsible for the reduction of the action potential duration (APD) (Guo et al., 1996), and a decrease of the pacemaker current (If) expression, likely associated with the disappearance of spontaneous activity (Cerbai et al., 1999). No data are available concerning the effects of prenatal CO exposure on cardiac development. The aim of this study was to evaluate and compare postnatal electrophysiological changes in ventricular myocytes isolated from male Wistar rats born from mothers exposed to 0 (CTR) or 150 ppm CO during pregnancy. Myocytes were isolated from rat hearts at different ages after birth (1 to 5, 8 to 15, 20 to 30 days) (Cerbai, et al., 1999). Patch-clamped cells were superfused with Tyrode's solutions pre-warmed to 35°C, appropriately modified to measure action potentials, Ito and If. Data are expressed as mean±s.e.m. Statistics was performed by means of ANOVA followed by the Student-Neuman-Keuls test. Probability of less than 0.05 was considered significant. Postnatal increase in membrane capacitance, an index of cell size, was similar in both groups: from 14±1 pF (n=38) to 60±5 pF (n=16) in CTR and from 15±1 pF (n=45) to 59±5 pF (n=26) in CO. While all measured values were not different in the two groups early after birth, differences were observed during growth. APD, measured at –50 mV, progressively decreased in CTR from 131±24 ms at 5 days (n=14) to 76±13 ms at 28 days (n=9) but not in CO rats, where it remained significantly prolonged (157±28 ms at 28 days, n=11, p<0.05 vs CTR). Similarly, Ito density, which significantly increased in CTR from 4.1±0.7 pA/pF (n=22) to 11.8±3.4 pA/pF (n=10) (p<0.01), remained low in CO rats (5.8±0.9 pA/pF at 28 days, n=17, p<0.01 vs CTR). The density of the pacemaker current If decreased by 75% from 1 to 28 days in CTR, but remained high in CO rats (at 28 days: 2.1 pS/pF (n=10) vs 0.7 pS/pF (n=7) in age-matched CTR, p<0.05). In conclusion, exposure to CO during the fetal life affects the normal process of electrophysiological maturation of the cardiac ventricular myocyte.