Principles of developmental cardiovascular physiology and pathophysiology

Fetal circulation

The fetal circulation is characterized by low systemic vascular resistance (SVR) with high systemic blood flow and high pulmonary vascular resistance with low pulmonary blood flow. Given the low oxygen tension of the fetus, the fetal circulation allows for preferential flow of the most oxygenated blood to the heart and brain, two of the three “vital organs”. ^,

With the placenta rather than the lungs being the organ of gas exchange, most of the right ventricular output is diverted through the patent ductus arteriosus (PDA) to the systemic circulation. In fact, the pulmonary blood flow only constitutes about 7–8% of the combined cardiac output in fetal lambs. However, Doppler and magnetic resonance imaging studies have shown that the proportion of combined cardiac output that supplies the lungs is higher in the human fetus (11–25%), with some studies reporting an increase in this proportion with advancing gestational age to a peak around 30 weeks’ gestation. In fetal life both ventricles contribute to the systemic blood flow, and the circulation therefore depends on the persistence of shunts via the foramen ovale and PDA between the systemic and pulmonary circuits, with the two circulations functioning in “parallel”. The right ventricle (RV) is the dominant pumping chamber, and its contribution to the combined cardiac output is about 60%. The combined cardiac output is in the range of 400–450 mL/kg/min in the fetus, which is much higher than the systemic flow after birth (about 200 mL/kg/min). Approximately one-third of the combined cardiac output (150 mL/kg/min) perfuses the placenta via the umbilical vessels. However, placental blood flow decreases to 21% of the combined cardiac output near term. The umbilical vein carries the oxygenated blood from the placenta though the portal veins and the ductus venosus to the inferior vena cava (IVC) and eventually to the heart. About 50% of oxygenated blood in the umbilical vein is shunted through the ductus venosus and IVC to the right atrium, where the oxygenated blood is preferentially directed to the left atrium through the patent foramen ovale. This percentage decreases as gestation advances. One of the unique characteristics of the fetal circulation is that arterial oxygen saturation (SaO ₂ ) is different between the upper and lower body. Having the most oxygenated blood in the left atrium ensures a supply of adequate oxygen to the heart and brain. Furthermore, in response to hypoxemia, most of the blood flow in the umbilical vein bypasses the portal circulation via the ductus venosus and again delivers the most oxygenated blood to the heart and brain.

Transitional physiology

Transition from the fetal to the postnatal type of circulation is a complex process. In the past decade research interest has again focused on cardiovascular and pulmonary adaptation at birth. Amongst others, animal and human studies have investigated the impact of the timing of cord clamping on cardiovascular and pulmonary transitional physiology. The findings of these studies have highlighted the importance of allowing for placental transfusion to take place and suggested that lung aeration should be established prior to umbilical cord clamping to ensure that the source of left ventricular (LV) preload gradually changes over from the placenta to the lungs. The maintenance of appropriate LV preload during the immediate hemodynamic transition from the fetal to the postnatal circulation has been shown to attenuate the abrupt decrease in preload and systemic blood flow seen with the practice of immediate cord clamping and is associated with improved postnatal hemodynamic stability and clinical outcomes ( Chapter 6 ). Among the clinical outcomes, improved postnatal transition, decreased need for blood transfusion, and lower incidence of intraventricular hemorrhage have been documented without significant untoward effects associated with delayed cord clamping in preterm infants. In addition, a decreased need for blood transfusion has been observed in term neonates, albeit with higher rates of jaundice and polycythemia reported. As discussed in Chapter 6 in detail, these findings have led to a departure from the traditional approach of immediate cord clamping and a move to delayed clamping of the cord for all newborns who are vigorous at birth in the absence of conditions preventing placental transfusion. Interestingly, cord milking seems to confer similar hemodynamic benefits to delayed cord clamping. ^, However, the finding of a higher rate of severe peri-/intraventricular hemorrhage (P/IVH) in the cord milking as compared to the delayed cord clamping group in preterm infants of <32 weeks’ gestation is concerning. The reason for the increased risk of P/IVH is unclear, although a rapid rise in cerebral blood flow (CBF) has been postulated as one of the possible etiological factors. In a subset of the patients in the trial by Katheria et al., cerebral oxygen saturation was also monitored in the delivery room and the findings were published in a separate paper. Interestingly, arterial oxygen saturation was higher in the cord milking group, without a difference in cerebral tissue oxygen saturation between the groups. Therefore, as a group, subjects who underwent cord milking might not have had excessive CBF. However, it is possible that in selected vulnerable individuals, a rapid increase in the preload and thus CBF plays a role. Therefore, while cord milking could reduce the risk of cerebral ischemia by rapidly increasing circulating blood volume and thus preload and therefore improving systemic blood flow, it may increase the risk of P/IVH through yet unidentified mechanism(s), and its use is currently not recommended.

After birth, the circulation changes from parallel to series, and thus the left and RV outputs must become equal. However, this process, especially in very preterm infants, is not complete for days or even weeks after birth due to the inability of the fetal channels to close in a timely manner. The persistence of the PDA alters the hemodynamics during transition and beyond and has been associated with severe and even refractory hypotension. ^, The impact of the PDA on pulmonary and systemic blood flow in the preterm infant is discussed in Chapter 16 . At birth, removal of the low-resistance placental circulation and the surge in catecholamines and other hormones increase the SVR. On the other hand, pulmonary vascular resistance (PVR) drops precipitously due to the act of breathing air and exposure of the pulmonary arteries to higher partial pressure of oxygen as compared to the very low level in utero. Organ blood flow also changes significantly. In the newborn lamb CBF drops in response to oxygen exposure. A drop in CBF in the first few minutes after birth in normal-term neonates has also been reported. This drop in CBF appears to be related, at least in part, to cerebral vasoconstriction in response to the increase in arterial blood oxygen content immediately after birth. In addition, the correlation between left-to-right PDA shunting and middle cerebral artery flow velocity (a surrogate for CBF) suggests a possible role of the ductus arteriosus in the observed reduction in CBF. Finally, especially in some very preterm neonates, the inability of the immature myocardium to pump against the suddenly increased SVR might lead to a transient decrease in systemic blood flow, which in turn could also contribute to the decrease in CBF ( Chapters 2 and 20 ).

Postnatal circulation