Ethanol exposure alters early cardiac function in the looping heart: a mechanism for congenital heart defects?

Abstract

Alcohol-induced congenital heart defects are frequently among the most life threatening and require surgical correction in newborns. The etiology of these defects, collectively known as fetal alcohol syndrome, has been the focus of much study, particularly involving cellular and molecular mechanisms. Few studies have addressed the influential role of altered cardiac function in early embryogenesis because of a lack of tools with the capability to assay tiny beating hearts. To overcome this gap in our understanding, we used optical coherence tomography (OCT), a nondestructive imaging modality capable of micrometer-scale resolution imaging, to rapidly and accurately map cardiovascular structure and hemodynamics in real time under physiological conditions. In this study, we exposed avian embryos to a single dose of alcohol/ethanol at gastrulation when the embryo is sensitive to the induction of birth defects. Late-stage hearts were analyzed using standard histological analysis with a focus on the atrio-ventricular valves. Early cardiac function was assayed using Doppler OCT, and structural analysis of the cardiac cushions was performed using OCT imaging. Our results indicated that ethanol-exposed embryos developed late-stage valvuloseptal defects. At early stages, they exhibited increased regurgitant flow and developed smaller atrio-ventricular cardiac cushions, compared with controls (uninjected and saline-injected embryos). The embryos also exhibited abnormal flexion/torsion of the body. Our evidence suggests that ethanol-induced alterations in early cardiac function have the potential to contribute to late-stage valve and septal defects, thus demonstrating that functional parameters may serve as early and sensitive gauges of cardiac normalcy and abnormalities.

Effects of a Single Dose of Ethanol on Survival Rate and Angiogenesis of Chick Embryo

“…We have found that at 13% EtOH the severe inhibition of the heart is observed. Some other studies have also reported the inhibition of heart at later development of chick embryo (Karunamuni, Gu et al 2014). This confirms the role of EtOH in inhibition of heart development.…”

“…CAM is formed on day 7 of incubation. EtOH has been reported to affect the process of angiogenesis in CAM assay using chick embryo as model organism ( ) and yolk sac blood vessels system of early staged chick embryos (Karunamuni, Gu et al 2014). In an elegant study, it was reported that moderate dose of EtOH has positive effects on development of embryo particularly on vasculature of embryo (Gu, Elam et al 2001).…”

The impact of sensory integration therapy on gross motor function in children after prenatal exposure to alcohol

“…In children whose mothers drank alcohol there are functional difficulties that are difficult to diagnose and classify, and often sensory integration dysfunction. For these children SI therapy is necessary and effective [10][11][12][13][14][15][16][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. This work, because of the breadth of statistical analysis, only shows the effects of SI therapy on gross motor function.…”

Fetal Alcohol Spectrum Disorder: Risk for Diabetes and Congenital Heart Defects

“…Karunamuni et al on this issue purport that as high as 54% of live-born children with FAS present with cardiac anomalies e.g. valvuloseptal defects and pulmonary stenosis [26] that can lead to developmental challenges and on-going medical care.…”