Chapter 55

During fetal life, the ductus arteriosus diverts blood away from the fluid-filled lungs toward the descending aorta and placenta. In full-term infants, obliteration of the ductus arteriosus takes place after birth through a process of vasoconstriction and anatomic remodeling. Premature infants frequently fail to close their ductus arteriosus. The clinical consequences of a patent ductus arteriosus (PDA) are related to the degree of left-to-right shunt through the PDA with its associated change in blood flow to the lungs, kidneys, and intestine.

In the full-term infant, closure of the ductus arteriosus occurs in 2 phases: (1) functional closure of the lumen within the first hours after birth by smooth muscle constriction and (2) anatomic occlusion of the lumen over the next several days due to extensive neointimal thickening and loss of smooth muscle cells from the inner muscle media.

### Balance between Vasoconstriction and Vasorelaxation

Although the fetal ductus arteriosus was originally thought to be a relatively passive structure that constricted after birth, it is now clear that, even in utero, the ductus has an active tone. Ductus arteriosus patency, therefore, is determined by the balance between dilating and constricting forces. The factors known to play a prominent role in ductus arteriosus regulation involve those that promote constriction (oxygen, endothelin, calcium channels, catecholamines, and Rho kinase) and those that oppose it (intraluminal pressure, prostaglandins, nitric oxide, carbon monoxide, potassium channels, and cyclic adenosine monophosphate and cyclic guanosine monophosphate). The relative importance of each of these factors depends on the intrauterine and extrauterine environment, the degree of ductus maturation, and the genetic background and species being studied.

### In Utero Regulation

The fetal ductus normally has a high level of intrinsic tone.1 The intrinsic tone is due to mechanisms that both depend on and are independent of extracellular calcium.1 The contractile proteins (smooth muscle myosin, calponin, and caldesmon) are more differentiated in the ductus than they are in adjacent fetal arteries.2-4 In addition, the fetal ductus arteriosus is more sensitive to the contractile effects of calcium than are the aorta and the pulmonary artery. Other potential factors contributing to ductus tone in utero include an increased Rho kinase activity in the ductus,6 endothelin-1,7 and catecholamines that circulate in high concentrations following birth.8-10

The factors that oppose ductus arteriosus constriction in utero are better understood. The elevated vascular pressure within the ductus lumen (due to the constricted pulmonary vascular bed) plays an important role in opposing ductus constriction.11 The fetal ductus also produces several vasodilators that maintain ductus patency. Vasodilator prostaglandins appear to be the dominant vasodilators that oppose ductus constriction in the later part of gestation.12 Inhibitors of prostaglandin synthesis constrict the fetal ductus both in vitro and in vivo.

Prostaglandin E2 is the most potent prostaglandin produced by the ductus and placenta,13,14 and appears to ...

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