A tissue culture model for studying ethanol toxicity on embryonic heart cells

Abstract

A tissue system in which fibroblasts and myocytes from chick embryonic hearts were separately maintained was used to study the toxicity of ethanol. To reproduce the teratogenic effects of acute, high concentrations of ethanol typical of "binge" drinking, an open tissue culture system was employed. With open cultures, the cells were initially exposed to peak alcohol levels for approximately 6 hr and were exposed to decreasing concentrations of ethanol for the remainder of each 24 hr period. After the first day of ethanol exposure, there was substantial cell loss in both fibroblast and myocyte cultures. Alcohol-induced cell loss was dose-dependent. Despite decreased cell density after the first day of ethanol exposure, the surviving cells differentiated into monolayers of fibroblasts or beating cardiac muscle fibers. However, both ethanol-exposed fibroblasts and myocytes appeared atrophic, that is, smaller and shrunken. Electrophoretic analysis or these ethanol-exposed fibroblast and myocyte cultures revealed specific reduction in the cellular contents of alpha-actinin, myosin, and actin. These decreases in cytoskeletal proteins may be responsible for the morphological abnormalities noted in these cells.

Influence of Prenatal Alcohol Exposure on Myocardial Contractile Function in Adult Rat Hearts: Role of Intracellular Calcium and Apoptosis

“…This is consistent with a teratogenic effect of ethanol and may contribute to the altered myocardial contractility in the ethanol group. Another potential explanation of depressed cardiac contractility may be that ethanol reduces specific cellular contents of actin and myosin in cardiac myocytes (Ni et al, 1992). These decreases in cytoskeletal and contractile proteins may contribute directly to the morphological abnormalities and depressed ventricular function.…”

“…Studies have shown that cardiac myocytes exposed to ethanol during embryogenesis did not mature morphologically or functionally (Adickes et al, 1990). Depressed growth of cardiac myocytes, reduction and delay in the development of myosin and actin, alteration in Ca 2+ transport, mitochondrial function, sarcoplasmic reticulum (SR) Ca 2+ uptake/binding as well as intracellular Ca 2+ homeostasis have been reported in several animal models of FAS (Ni et al, 1992;Staley and Tobin, 1992;Fuseler, 1993;Syslak et al, 1994;Altura et al, 1996).…”

Chronic ethanol increases calcium/calmodulin-dependent protein kinaseIIδ gene expression and decreases monoamine oxidase amount in rat heart muscles: Rescue effect of Zingiber officinale (ginger) extract

“…In addition, reduced cardiac contractility, cardiac output, left ventricular ejection fraction, and abnormalities of the great vessels result from chronic ethanol exposure in animal and human models ( 5 - 7 ). Furthermore, alteration in Ca 2+ transport, mitochondrial function, sarcoplasmic reticulum Ca 2+ uptake/binding, and Ca 2+ homeostasis have been demonstrated by several previous studies ( 3 , 8 , 9 ). Although different aspects of functional and structural cardiac alterations have been identified by early and recent studies, the precise mediating steps between exposure of heart muscle to ethanol and initiation of the cascade of responses leading to cardiac abnormality have not yet been completely clarified.…”

“…Recent studies have demonstrated that chronic ethanol exposure leads to a wide range of functional and structural abnormities in the cardiovascular system ( 1 - 3 ). From the structural aspect, heart tissue fibrosis decreases the myocyte number, disrupts myofibrillar structure, and causes left ventricular hypertrophy and myocardial infarction.…”