P0413 - Teratogenic Effects of Prenatal Alcohol Exposure on Cardiac Innervation

Alcohol exposure during embryonic development can damage neural crest cells, precursors of the autonomic nervous system. Abnormalities of cardiac innervation are known to result in heart disease, arrhythmias, and are implicated in sudden infant death syndrome (SIDS), the sudden and unexplained death of an infant usually during sleep. Children exposed to alcohol in utero have abnormal heart rate responses to tilt table testing, suggesting dysfunction in the autonomic control of the heart and increased rates of SIDS. We tested our hypothesis that prenatal alcohol exposure would result in changes in heart innervation that could explain this autonomic dysfunction.
Quail eggs were incubated at 38oC in a humidified incubator. Eggs were injected with 40 l PBS (control) or 40 l of 50% ethanol at 24 hours, then allowed to incubate until dissection at 8 days. This ethanol administration is equivalent to one bout of binge drinking during early first trimester and results in fetal alcohol spectrum disorder phenotypes.
Using fluorescently labeled TUJ1, an antibody that specifically binds neuronal cytoskeletal components, we immunostained intact hearts and captured images of the thoracic nerve, a cardiac branch of the vagus, which runs the length of the pulmonary artery (see Figure 1). A binary system was used to evaluate the presence or absence of a split in this nerve branch.
Cohorts included 13 control (PBS) hearts and 20 exposed to ethanol. The Fisher’s exact test demonstrated a statistically significant increase in splitting of the thoracic nerve after alcohol exposure (p= 0.038) (see table 1). Qualitative differences were noted in the pattern and area of the nerve plexus on the heart that will require a more complex quantitative analysis.

We demonstrated that prenatal alcohol exposure resulted in embryos exhibiting a split of the major nerve that innervates the heart, even in those with structurally normal hearts. Changes in structural innervation can have significant clinical effects including, changes in cardiac function, development of arrhythmias and changes in autonomic response. Inability to increase heart rate and respond to periods of stress has been associated with SIDS, potentially linking these findings to a clinically relevant event. This finding may change the management of those with structurally normal hearts exposed to alcohol in utero, requiring long term follow up, and further investigation of cardiac autonomic function.