Indomethacin and renal function in premature infants with persistent patent ductus arteriosus

Cifuentes, Raul F.; Olley, Peter M.; Balfe, J. Williamson; Radde, Ingeborg C.; Soldin, S J

doi:10.1016/s0022-3476(79)80775-1

Cited by 143 publications

(49 citation statements)

References 23 publications

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“…A greater contribution of prostanoids to perinatal hemodynamics than to hemodynamics of adult animals is suggested by several lines of evidence, including: (1) the elevated concentration of the prostacydin hydrolysis product, 6-keto-PGFi a , in fetal and neonatal arterial plasma when compared to the adult (Kaapa et al, 1982;Leffler et al, 1982); (2) the ability of cydooxygenase inhibitors to dose the ductus arteriosus in the fetus or neonate (Friedman et al, 1976;, suggesting that prostanoids are important in the maintenance of patency of the ductus arteriosus in the fetus; (3) data supporting the hypothesis that pulmonary prostacyclin production contributes to the decline in pulmonary vascular resistance at the onset of ventilation at birth (Leffler et al, 1978;Leffler and Hessler, 1979;Leffler et al, 1980;Leffler and Hessler, 1981;Leffler et al, 1984); and (4) the transient decline in renal function that typically accompanies treatment of neonates with cydooxygenase inhibitors (Cifuentes et al, 1979;Friedman and Kirkpatrick, 1980), in contrast to the negligible effects of cydooxygenase inhibition upon renal function in adults. However, since the effect of indomethacin upon pial arterial diameter or cerebral blood flow in adult pigs has not been examined, it is not known whether the response of the newborn pig pial vessels to indomethacin treatment is greater than that of the adult pigs.…”

Section: Discussionmentioning

confidence: 99%

Prostanoids in cortical subarachnoid cerebrospinal fluid and pial arterial diameter in newborn pigs.

Leffler¹,

Busija²

1985

Circulation Research

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SUMMARY. These studies were designed to investigate the relationship between ceTebral prostanoid synthesis and pial arterial caliber in chloralose-anesthetized newborn pigs with normal blood gases and pH and during combined arterial hypoxia and hypercapnia. Piglets less than 5 days old were equipped with closed cranial windows to allow direct observation of pial vessels, application of prostaglandin E^ and sampling of cortical subarachnoid cerebrospinal fluid. We found that prostanoids accumulate in cerebrospinal fluid on the cortical surface. The only prostanoid detected in arterial blood was 6-keto-prostaglandin Fi o [442 ± 74 pg/ml (radioimmunoassay)]. Only small quantities of 6-keto-prostaglandin F la (214 ± 53 pg/ml) and thromboxane B? (122 ± 18 pg/ml) were found in cerebrospinal fluid from the cisterna magna. Higher concentrations of 6-keto-prostaglandin Fi o (1056 ± 159 pg/ml), thromboxane B 2 (229 ± 64 pg/ml), and prostaglandin E 2 (4235 ± 269 pg/ml) were found in cortical subarachnoid fluid. In contrast to arterial and asternal concentrations, the concentrations of 6-keto-prostaglandin F ]

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Section: Discussionmentioning

confidence: 99%

Prostanoids in cortical subarachnoid cerebrospinal fluid and pial arterial diameter in newborn pigs.

Leffler¹,

Busija²

1985

Circulation Research

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“…The use of indomethacin treatment to suppress prostaglandin production in infants with patent ductus arteriosus often leads to water retention (40,41). In the presence of drugs that suppress endogenous prostaglandin production, AQP2 will remain in the plasma membrane (19).…”

Section: Kidney Aqpsmentioning

confidence: 99%

Water Channels (Aquaporins) and Their Role for Postnatal Adaptation

2005

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Birth is a transition from an underwater life in the uterus to a terrestrial life in a milieu where supply of water is limited. Rapid adaptation to the new environment is crucial for survival and health of infants. The discovery of a family of moleculesaquaporin (AQP) water channels-that are responsible for regulated water transport across cell membranes has made it possible to identify the molecular mechanisms behind the postnatal homeostatic adaptation and to better understand water imbalance-related disorders in infancy and childhood. Water is a prerequisite for life. Water molecules are polar, which allows them to easily form hydrogen bonds with each other and with other molecules. They serve as excellent solvents for a variety of polar substances in the cells. Water provides solvent shells around charged groups of biopolymers. These shells are essential for the biologic activity of proteins (1).It took hundreds of millions years for ancient vertebrate organisms to adapt from a life with unrestricted water supply to a terrestrial life. This adaptation has involved the development of numerous intricate mechanisms and regulatory systems that allow animals to exist in air environment, where supply of water is more or less limited. Now it takes mammals a few minutes to make the transition from an underwater existence in the uterus to a postnatal terrestrial life. The first immediate task a newborn infant has to deal with is rapid removal of water out of lung air spaces. Maturation of kidney concentrating capacity occurs in humans during the first year of life. The capacity to maintain a proper water balance in the brain and to protect from brain edema may take even longer time.Water comprises about 60% of our body weight. In newborn full-term infants, total body water fraction is approximately 75%, and in preterm babies approximately 80 -85% of their body mass (2). The ratio between extracellular and intracellular water content changes dramatically in the postnatal period (Fig. 1). Shortly after birth, the body water mass rapidly decreases. This decrease is mainly due to a reduction of extracellular water fraction, which decreases from about 45% to 30% of total body mass during the first 3 mo of life.As late as in 1990, little was known about the molecular mechanism regulating total body water content and the distribution of water between the extracellular and intracellular space. The discovery of integral membrane proteins that function as water channels (3), resulted in a paradigm shift for the understanding of the mechanisms behind transmembrane water transport, water redistribution processes after birth, and many pathologic conditions related to disturbances in water homeostasis.More than 10 isoforms of water channels, now named AQPs, have been identified in humans to date. Most of them have a common molecular structure, with six transmembrane domains and intracellular NH 2 -and COOH-termini. Functionally, AQPs can be divided into two subfamilies-aquaporins, specialized on transport of water, and aquaglycero...

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“…7 The prostanoid system could contribute to maintenance of cerebral blood flow at low arterial pressures in the newborn since the prostanoid system appears to be more prominent in the neonate than in the older individual. For example, the plasma levels of the hy-Treatment of newborn human infants with prostanoid cyclooxygenase inhibitors to close the patent ductus arteriosis frequently causes transient renal dysfunction, 10 " in contrast to negligible effects on adults. A role for prostanoids in perinatal pulmonary vascular transition has been established.…”

Section: Maintenance Of Cerebral Circulation During Hemorrhagic Hypotmentioning

confidence: 99%

Maintenance of cerebral circulation during hemorrhagic hypotension in newborn pigs: role of prostanoids.

Leffler¹,

Busija²,

Beasley³

et al. 1986

Circulation Research

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The possibility that the prostanoid system contributes to the capability of the newborn piglet to maintain cerebral blood flow and cerebral metabolic rate during hypotension was investigated. The effect of hemorrhage on net (arterial-to-venous) cerebral prostacyclin production and the effects of indomethacin on cerebral hemodynamic response to hemorrhage and on the cerebral oxygen utilization following hemorrhage were determined in chronically Instrumented, unanesthetized newborn pigs. Hemorrhage decreased arterial pressure about 35% but did not affect cerebral blood flow or cerebral O 2 consumption. Hemorrhage was accompanied by an increase in net cerebral 6-ket0-PGF lo production from 4.0 ±1.1 to 15.3 ± 4.9 ng/lOOgmin (mean ± SEM). Indomethacin treatment of piglets following hemorrhage inhibited the net cerebral production of 6-keto-PGF la and caused a decrease in blood flow (=40%) to all brain regions within 20 minutes. The decrease in cerebral blood flow was the result of an increase in cerebral vascular resistance of 57 and 180%, 20 and 40 minutes post treatment, respectively. Cerebral O 2 consumption was reduced from 2.5 ± 0.3 ml/100 g-min to 1.5 ± 0.3 ml/100 gmin 20 minutes following treatment of hemorrhaged piglets with indomethacin and to 1.1 ± 0.3 ml/100 g-min 40 minutes after treatment. Six of 8 piglets for whom the data were recorded that were administered indomethacin following hemorrhage became comatose with cerebral O 2 consumption of 0.4 ± 0.1 ml Oj/100 g-min by 40 minutes after treatment. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn. (Circulation Research 1986;59:562-567) A CHARACTERISTIC feature of the cerebral cir-/\ culation is that blood flow is maintained rela-A. X. tively constant over a wide range of perfusion pressure. In adults, autoregulatory mechanisms prevent cerebral blood flow from changing appreciably over the arterial pressure range of approximately 60-150 mm Hg.u Cerebral autoregulation in fetuses and newboms extends to lower arterial pressures than in adults, 3 " 5 and may reflect adaptations of the cerebral circulation of fetuses and neonates to lower resting arterial pressure.Various mechanisms have been suggested to account for cerebral autoregulation, including neural, myogenic and metabolic.6 However, intriguing evidence suggests a possible role of prostanoids in maintenance of cerebral blood flow following hemorrhage. 7The prostanoid system could contribute to maintenance of cerebral blood flow at low arterial pressures in the newborn since the prostanoid system appears to be more prominent in the neonate than in the older individual. For example, the plasma levels of the hy-

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Indomethacin and renal function in premature infants with persistent patent ductus arteriosus

Cited by 143 publications

References 23 publications

Prostanoids in cortical subarachnoid cerebrospinal fluid and pial arterial diameter in newborn pigs.

Prostanoids in cortical subarachnoid cerebrospinal fluid and pial arterial diameter in newborn pigs.

Water Channels (Aquaporins) and Their Role for Postnatal Adaptation

Maintenance of cerebral circulation during hemorrhagic hypotension in newborn pigs: role of prostanoids.

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