Patent Ductus Arteriosus　– A Complex Problem in Need of a Solid Conceptual Foundation –

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp contrast, among premature infants, premature birth interrupts the normal maturation of ductal contractile mechanisms, leaving the ductus more susceptible to vasodilatory factors. 7 Although prostaglandins (PGs) are considered the dominant vasodilators opposing ductal constriction in the later part of gestation, 6 Kajimura et al suggest an even greater complexity in the mechanisms regulating ductus arteriosus, wherein • NO also plays an critical role in ductal patency, particularly in the setting of maternal chorioamnionitis. Another important finding in the present study by Kajimura et al is that use of a NOS inhibitor precursor, L-N G -nitroarginine methyl ester hydrochloride (L-NAME, which undergoes hydrolysis in vivo to produce L-N G -nitroarginine, the functional NOS inhibitor) prevented delayed closure of the ductus after birth in pups from LPS-injected rats. 5 These observations suggest that maternal risk factors, such as chorioamnionitis, can influence the mechanisms of DA regulation, wherein the use of treatments interfering with • NO synthesis or function could be useful adjuncts to achieve PDA closure in this subpopulation of infants, and provide a basis for more targeted interventions on the PDA. 5 To that end, Seidner et al showed, among preterm newborn baboons, that the combined use of indomethacin and L-NAME produces a much greater degree of ductus constriction than does indomethacin alone, corresponding to the synergistic interaction of • NO and PG in ductal regulation. 10 However, • NO blockade may not be therapeutically beneficial, because of the nonspecific nature of currently available treatments. 7 Although a phase I and II study by Keller et al showed higher rates of ductal closure with combined L-N G -monomethyl Arginine citrate (L-NMMA, a he ductus arteriosus (DA) is an essential component of the fetal circulation, shunting blood away from the high-resistance pulmonary vascular bed toward the placenta. At birth, the placental circulation is removed, and the lungs become the source of oxygenated blood; thus, shunting through the ductus becomes potentially harmful. Although closure of the ductus occurs within hours after birth in the majority of term infants, a persistent patent DA (PDA), defined as a ductus that fails to close within 72 h postnatal age, is seen in the majority of infants born extremely premature (<28 weeks of gestation). 1 A PDA is often a precursor to heart failure, prolonged ventilator dependency, necrotizing enterocolitis, and bronchopulmonary dysplasia. Moreover, recent evidence shows higher mortality in infants with a PDA than in agematched infants with closed ductus. 2 However, the extent to which these adverse consequences are attributable to the PDA remains unknown. Despite nearly 6 decades of basic and clinical research, fundamental questions on the evaluation and treatment of PDA in preterm infants remain unanswered. Article p 703Rather than approaching the PDA as an ...

Early prediction of spontaneous Patent Ductus Arteriosus (PDA) closure and PDA-associated outcomes: a prospective cohort investigation

“…Vocal-cord paralysis and post-operative hemodynamic instability are also potential risks [38–40]. PDA closure via heart catheterization is potentially less-invasive [41–44]; however, it remains understudied and carries potential complications including arterial injury [41–43]. Since all forms of PDA closure are expensive and associated with adverse effects [38, 41–43, 45, 46], treatment harms may outweigh benefits, especially for the majority of infants destined for early, spontaneous PDA closure.…”

Altered plasma proteins released from platelets and endothelial cells are associated with human patent ductus arteriosus

“…The ductus arteriosus (DA) is a normal and essential structure in fetal circulation. It is highly patent and shunts more than half of the deoxygenated cardiac output into the descending aorta (Backes & Smith, ; Leonhardt et al, ; Matsushita, Endo, & Fujita, ). Fetal patency of the DA is controlled by many factors, including low fetal oxygen tension (Heymann & Rudolf, ), nitric oxide (NO; Echtler et al, ; Kajino et al, ), and cyclooxygenase‐mediated products of arachidonic acid metabolism, particularly prostaglandin E 2 (PGE 2 ; Coggins et al, ).…”