The Neonatal Transition of the Right Ventricle

Abstract

The pulmonary circulation undergoes a dramatic transition at birth, which includes a marked fall in pulmonary vascular resistance (PVR) to accommodate an eight- to tenfold increase in pulmonary blood flow. Failure to achieve or sustain this normal drop in PVR leads to the syndrome of persistent pulmonary hypertension of the newborn (PPHN), which is characterized by profound hypoxemia due to extra-pulmonary shunt, poor cardiac output, and significant morbidity and mortality. The fetal myocardium must also adapt rapidly during the transition, and the right ventricle (RV) undergoes striking functional and structural changes after birth. The RV serves as the ``systemic ventricle'' in utero, as most of the RV output crosses the widely patent DA and provides 2/3 of combined ventricular output in the normal fetus. Increased systemic vascular resistance, the marked fall in PVR, and functional closure of the ``fetal channels'' account for the progressive decrease in RV wall thickness and increase in LV mass after birth. Unlike changes in the RV during the normal transition, RV hypertrophy persists in the setting of sustained elevations of PVR due to birth at altitude, PPHN, congenital heart disease, and other cardiopulmonary disorders. In addition to these striking physiologic changes, the neonatal transition of the RV is further characterized by remarkable cellular, molecular, and metabolic adaptations. The fetal heart grows and develops during normal intrauterine life at low oxygen tensions that would induce severe hypoxic stress during postnatal life, yet the fetus thrives and is well-prepared for the normal transition at birth. Insights into mechanisms underlying the normal metabolic and functional transition from fetal to neonatal life are not only important for better understanding of neonatal cardiopulmonary diseases, but will also provide insights into adaptive and maladaptive responses in the adult RV.