Impact of Chronic Fetal Hypoxia and Inflammation on Cardiac Pacemaker Cell Development

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  Figure 1. Visual abstract. Adverse intrauterine conditions, such as infection, hypoxia, ischemia, and malnutrition, reprogram the autonomic nervous system (ANS). Together, these adversities impact the three key components of the cardiac pacemaker synchronization (CPS), which are shown in the center blue box (see below for details). The impact is proposed to alter physiology across three conceptual dimensions identified by blue-hued hexagons as follows: (1) direct alteration of the ion channels’ function; (2) change in the spatial organization of cardiac pacemaker cells, i.e., their channel microdomains and the isolating tissue; and (3) reduction in the energy availability in brown adipose tissue. In this review, we discuss known biomarkers that represent the ion channel activity, transcription factors, gap junction genes, and novel proteins, whose role is yet to be understood. These biomarkers can be engaged to quantify the compound effect of a greater vulnerability to future insults. This is identified in the left-hand side under sequelae.