**2.1. Embryology, anatomy, and physiology**

The RV and LV have different embryological origins and diverge early in development. The RV derives from the anterior (secondary) heart field, while the LV derives from the early heart tube (primary heart field) [9]. This early divergence is transcriptionally regulated, and several transcription factors have been identified which are responsible for the chamber-specific development including Hand2 and Tbx20 [10]. During gestation, the RV functions as the systemic pump. After birth, the RV becomes coupled to the low-pressure pulmonary circulation. As the ductus arteriosus and foramen ovale close, peripheral vascular resistance (PVR) decreases, leading to an increase in RV compliance, regression of muscle mass, and shifting of the interventricular septum toward the RV, resulting in a concave shape of the ventricle in adulthood. Consequently, right sided pressures are significantly lower than the systemically-coupled left sided pressures. Due to its coupling to a low-pressure circuit, the RV is approximately 1/3 the thickness of the LV. As a result of lower pressures and wall stress, the RV has a lower O<sup>2</sup> requirement both at rest and during exercise. Consistent with a lower workload, coronary blood flow and O<sup>2</sup> delivery to the RV are comparatively lower than the LV [11]. At rest, the LV extracts 75% of O<sup>2</sup> and the RV ~50% of the available coronary O<sup>2</sup> . These basal differences in oxygen uptake are important under periods of physiological or pathological stress, particularly those in which oxygen availability changes. Further, the ventricles can adapt to changes in oxygen availability through different mechanisms, with the RV meeting O<sup>2</sup> demands by either increasing coronary flow or by increased O<sup>2</sup> extraction [12], whereas the LV primarily increases coronary flow to match demand [13]. These data are consistent with the response of the ventricles to pathological insult, which will be discussed in greater detail below.
