Prenatal ethanol exposure alters ventricular myocyte contractile function in the offspring of rats: Influence of maternal Mg²⁺ supplementation

Fetal alcohol syndrome (FAS) is often associated with cardiac hypertrophy and impaired ventricular function in a manner similar to postnatal chronic alcohol ingestion. Chronic alcoholism has been shown to lead to hypomagnesemia, and dietary Mg²⁺ supplementation was shown to ameliorate ethanol-induced cardiovascular dysfunction such as hypertension. However, the role of gestational Mg²⁺ supplementation on FAS-related cardiac dysfunction is unknown. This study was conducted to examine the influence of gestational dietary Mg²⁺ supplementation on prenatal ethanol exposure-induced cardiac contractile response at the ventricular myocyte level. Timed-pregnancy female rats were fed from gestation day 2 with liquid diets containing 0.13 g/L Mg²⁺ supplemented with ethanol (36%) or additional Mg²⁺ (0.52 g/L), or both. The pups were maintained on standard rat chow through adulthood, and ventricular myocytes were isolated and stimulated to contract at 0.5 Hz. Mechanical properties were evaluated using an IonOptix™ soft-edge system, and intracellular Ca²⁺ transients were measured as changes in fura-2 fluorescence intensity (ΔFFI). Offspring from all groups displayed similar growth curves. Myocytes from the ethanol group exhibited reduced cell length, enhanced peak shortening (PS), and shortened time to 90% relengthening (TR₉₀) associated with a normal ΔFFI and time to PS (TPS). Mg²⁺ reverted the prenatal ethanol-induced alteration in PS and maximal velocity of relengthening. However, it shortened TPS and TR₉₀, and altered the ΔFFI, as well as Ca²⁺ decay rate by itself. Additionally, myocytes from the ethanol group exhibited impaired responsiveness to increased extracellular Ca ²⁺ or stimulating frequency, which were restored by gestational Mg²⁺ supplementation. These data suggest that although gestational Mg²⁺ supplementation may be beneficial to certain cardiac contractile dysfunctions in offspring of alcoholic mothers, caution must be taken, as Mg²⁺ supplementation affects cell mechanics itself.