The ductus arteriosus in the preterm infant: Histologic and clinical observations

Abstract

In order to elucidate some of the unexplained phenomena in prolonged patency of the ductus arteriosus in preterm infants, the histology of the ductus was studied in 27 eases. Some PROLONGED PATENCY of the ductus arteriosus in preterm infants with a large left-to-right shunt often leads to cardiopulmonary distress. Its increased incidence over the last few years ~ is probably due to improved neonatal intensive care. A satisfactory explanation of the cause of delayed ductal closure in preterm infants has not been found. Sooner or later spontaneous closure is seen in most infants. Immediate closure of the ductus after birth in very immature infants may also occur. 1-~ In recent years pharmacologic closure with indomethacin has been attempted, >" and closure may be obtained in this way. However, both lack of response and reopening after initial contraction with indomethacin have been observed. ~-~ To contribute to a better understanding of the above mentioned problems, we did a histologic study of the ductus tissue of preterm human infants. SUBJECTS AND METHODStThe ducts of 27 preterm infants, with gestational ages ranging from 24 to 37 weeks and varying in age from 10 tTabulated clinical data available on special request. hours to 5F2 months, were studied. The ducts, with the adjacent parts of the aorta and pulmonary artery, were removed at autopsy. The material was fixed in alcohol/ glycerine and prepared routinely for histologic examination. All specimens were completely serially sectioned and the sections stained alternately with hematoxylin-eosin, azan, resorcin fuchsin, and van Gieson elastic tissue stain. See related article, p. 94.For comparison, we also studied 15 ducts from fetuses with a gestational age of 16 to 23 weeks, who either were born dead or did not live longer than one hour. Furthermore, 40 ducts from term infants ranging in age from 0 hours to several years, were investigated. Some of the results of this last group have been described previouslyY lo These latter studies indicated that in case of permanent patency of the ductus, also referred to as persistent patency, there is a primary anatomic defect of the ductus.The bistologic findings in the preterm infants were related to clinical data, birth weight, asphyxia at birth, incidence of respiratory distress, use of assisted ventilation, prolonged patency of the ductus, and cause of death. All infants had been admitted to a neonataI intensive care unit. The clinical recognition of patency of the ductus arteriosus during the first week of life was sometimes very difficult. It was often impossible to separate those infants

Recent Advances Concerning the Molecular Mechanism of Patent Ductus Arteriosus

“…These changes in DA structure have been well investigated both in rodents and in humans. Given that intimal thickening is poorly developed in patients with PDA and in animal models of PDA (Gittenberger-de Groot, 1980;Gittenberger-de Groot,1985;Tada,1985), this process must play a critical role in permanent closure of the DA after birth. Therefore, a common molecular mechanism must underlie the development of intimal thickening of the DA in humans and animals alike.…”

Regulation of vascular tone and remodeling of the ductus arteriosus

“…Intimal thickening is developed in mature rat DA on the 21 st day of gestation, while it is lacked in immature DA on the19 th day of gestation. Since intimal thickening is poorly developed in human patent DA patients and animal models of patent DA (Gittenberger-de Groot et al, 1980;Gittenberger-de Groot et al, 1985;Tada et al, 1985), this process plays an important role in permanent closure of the DA after birth.…”

Progerin Expression during Normal Closure of the Human Ductus Arteriosus: A Case of Premature Ageing?

“…After birth, the DA contracts, and this physiological closure is followed by definitive anatomical closure. Ultimately, the DA will be remodeled into a fibrous strand [1,2]. The physiological closure is regulated by many substances in which prostaglandins play an important role [3].…”

“…The physiological closure is regulated by many substances in which prostaglandins play an important role [3]. The onset of anatomical closure in the human fetus starts already in the second trimester of gestation with blebbing of the endothelium and formation of intimal thickening [2]. The degenerative changes in the media, in which cytolytic necrosis and apoptosis play an important role [4], start immediately after birth.…”

“…Usually, this resolves spontaneously within a few days to weeks after birth. The process might be enhanced by providing prostaglandin inhibitors like indomethacin [2]. Another reason for non-closure resulting in a persistent DA (PDA) may be structural abnormalities, in most cases based on an elastin deposition problem [3].…”