
Research Interests: Cardiology, Cell Biology, Developmental Biology, Neonatology, Neonatal Cardiology Summary: The ductus arteriosus is a vital fetal blood vessel that diverts blood away from the fetus's lungs and towards the placenta during life inside the uterus. After birth it is essential that the ductus arteriosus constricts and obliterates itself so that the normal postnatal pattern of blood flow can be established. Essentially all full term infants will have closed their ductus by the third day after birth. Preterm infants of less than 30 weeks gestation have a high chance of having a persistently open or patent ductus arteriosus (PDA). If the ductus arteriosus remains open it contributes to the development of several neonatal morbidities: prolonged ventilator dependency, pulmonary hemorrhage, pulmonary edema, chronic lung disease and necrotizing enterocolitis. Our laboratory has been studying the factors that regulate normal closure of the ductus arteriosus in full term infants and abnormal persistent ductal patency in preterm infants. Approaches used to study this problem are: controlled clinical trials, integrated whole animal physiology, in vitro organ culture, and cell biology.
Publications
Early Treatment of the Presymptomatic Patent Ductus Arteriosus.
Urinary Acetaminophen Metabolites and Clinical Outcomes in Extremely Premature Infants.
Betamethasone treatment-to-delivery interval, retreatment, and severe intraventricular hemorrhage in infants <28 weeks' gestation.
Prophylactic indomethacin and the risk of serious pulmonary hemorrhages in preterm infants less than 28 weeks' gestation.
Prophylactic Indomethacin in Infants Born Extremely Preterm: Risks and Benefits Revisited.
Patent Ductus Arteriosus in Premature Infants: Clinical Trials and Equipoise.
Prophylactic indomethacin, antenatal betamethasone, and the risk of intestinal perforation in infants <28 weeks' gestation.
Patent ductus arteriosus (PDA) and pulmonary morbidity: can early targeted pharmacologic PDA treatment decrease the risk of bronchopulmonary dysplasia?
Patent ductus arteriosus and the risk of bronchopulmonary dysplasia-associated pulmonary hypertension.
Effects of prophylactic indomethacin on morbidity and mortality in infants <25 weeks' gestation: a protocol driven intention to treat analysis.
An Update on Patent Ductus Arteriosus and What is Coming Next.
Management of persistent ductus arteriosus in very premature neonates. Results of the French TRIOCAPI trial, perspectives for clinicians, and subsequent studies on this topic.
Corrigendum: Platelet Counts and Patent Ductus Arteriosus in Preterm Infants: An Updated Systematic Review and Meta-Analysis.
Interactions between PDA-associated polymorphisms and genetic ancestry alter ductus arteriosus gene expression.
Patent ductus arteriosus, tracheal ventilation, and the risk of bronchopulmonary dysplasia.
Reply.
Platelet Counts and Patent Ductus Arteriosus in Preterm Infants: An Updated Systematic Review and Meta-Analysis.
Effect of Early Targeted Treatment of Ductus Arteriosus with Ibuprofen on Survival Without Cerebral Palsy at 2 Years in Infants with Extreme Prematurity: A Randomized Clinical Trial.
Prolonged Tracheal Intubation and the Association Between Patent Ductus Arteriosus and Bronchopulmonary Dysplasia: A Secondary Analysis of the PDA-TOLERATE trial.
The effect of prolonged tracheal intubation on the association between patent ductus arteriosus and bronchopulmonary dysplasia (grades 2 and 3).
A role for neonatal bacteremia in deaths due to intestinal perforation: spontaneous intestinal perforation compared with perforated necrotizing enterocolitis.
Paracetamol (Acetaminophen) for Patent Ductus Arteriosus: Where Do We Stand?
Relationship between Duration of Infant Exposure to a Moderate-to-Large Patent Ductus Arteriosus Shunt and the Risk of Developing Bronchopulmonary Dysplasia or Death Before 36 Weeks.
Transcatheter patent ductus arteriosus closure-will history repeat itself?
CYP2C9*2 is associated with indomethacin treatment failure for patent ductus arteriosus.
Lack of Equipoise in the PDA-TOLERATE Trial: A Comparison of Eligible Infants Enrolled in the Trial and Those Treated Outside the Trial.
Comparative effectiveness of drugs used to constrict the patent ductus arteriosus: a secondary analysis of the PDA-TOLERATE trial (NCT01958320).
Intrauterine Growth Restriction and Patent Ductus Arteriosus in Very and Extremely Preterm Infants: A Systematic Review and Meta-Analysis.
PDA-TOLERATE Trial: An Exploratory Randomized Controlled Trial of Treatment of Moderate-to-Large Patent Ductus Arteriosus at 1 Week of Age.
Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data.
Patent ductus arteriosus, its treatments, and the risks of pulmonary morbidity.
Transcriptional profiling of the ductus arteriosus: Comparison of rodent microarrays and human RNA sequencing.
Bronchopulmonary Dysplasia: Executive Summary of a Workshop.
Treatment and Nontreatment of the Patent Ductus Arteriosus: Identifying Their Roles in Neonatal Morbidity.
Response to Coceani et al.
Prophylactic Indomethacin Compared with Delayed Conservative Management of the Patent Ductus Arteriosus in Extremely Preterm Infants: Effects on Neonatal Outcomes.
Effects of Prophylactic Indomethacin on Vasopressor-Dependent Hypotension in Extremely Preterm Infants.
Antenatal Betamethasone: A Prolonged Time Interval from Administration to Delivery Is Associated with an Increased Incidence of Severe Intraventricular Hemorrhage in Infants Born before 28 Weeks Gestation.
Microarray gene expression analysis in ovine ductus arteriosus during fetal development and birth transition.
Clamp late and maintain perfusion (CLAMP) policy: delayed cord clamping in preterm infants.
Effects of Advancing Gestation and Non-Caucasian Race on Ductus Arteriosus Gene Expression.
Platelet Counts and Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis.
Predicting the Need for Home Oxygen Therapy in Preterm Infants Born Before 28 Weeks' Gestation.
Catecholamine-resistant hypotension and myocardial performance following patent ductus arteriosus ligation.
Managing the patent ductus arteriosus: current treatment options.
Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones.
Obstetricians' attitudes and beliefs regarding umbilical cord clamping.
Superior mesenteric artery blood flow velocities following medical treatment of a patent ductus arteriosus.
The role of patent ductus arteriosus and its treatments in the development of bronchopulmonary dysplasia.
Enteral feeding during indomethacin and ibuprofen treatment of a patent ductus arteriosus.
Dopamine-resistant hypotension and severe retinopathy of prematurity.
Neurodevelopmental outcomes following two different treatment approaches (early ligation and selective ligation) for patent ductus arteriosus.
Surgical ligation of the patent ductus arteriosus: treatment or morbidity?
Patent ductus arteriosus: are current neonatal treatment options better or worse than no treatment at all?
Effects of ibuprofen treatment on the developing preterm baboon kidney.
Anatomic closure of the premature patent ductus arteriosus: The role of CD14+/CD163+ mononuclear cells and VEGF in neointimal mound formation.
Patent ductus arteriosus ligation alters pulmonary gene expression in preterm baboons.
Relationship between circulating platelet counts and ductus arteriosus patency after indomethacin treatment.
Ibuprofen treatment for closure of patent ductus arteriosus is not associated with increased risk of neuropathology.
Patterns of gene expression in the ductus arteriosus are related to environmental and genetic risk factors for persistent ductus patency.
Early surgical ligation versus a conservative approach for management of patent ductus arteriosus that fails to close after indomethacin treatment.
How useful are B-type natriuretic peptide measurements for monitoring changes in patent ductus arteriosus shunt magnitude?
Feeding practices and patent ductus arteriosus ligation preferences-are they related?
Vessel remodeling in the newborn: platelets fill the gap.
Chronic in utero cyclooxygenase inhibition alters PGE2-regulated ductus arteriosus contractile pathways and prevents postnatal closure.
The role of patent ductus arteriosus ligation in bronchopulmonary dysplasia: reexamining a randomized controlled trial.
Oxygen-induced tension in the sheep ductus arteriosus: effects of gestation on potassium and calcium channel regulation.
Developmental and neuropathological consequences of ductal ligation in the preterm baboon.
Postnatal estradiol up-regulates lung nitric oxide synthases and improves lung function in bronchopulmonary dysplasia.
A randomized, double-blind, placebo-controlled trial on intravenous ibuprofen L-lysine for the early closure of nonsymptomatic patent ductus arteriosus within 72 hours of birth in extremely low-birth-weight infants.
Effects of a patent ductus arteriosus on postprandial mesenteric perfusion in premature baboons.
Expression, activity, and function of phosphodiesterases in the mature and immature ductus arteriosus.
Transcriptional regulation during development of the ductus arteriosus.
Increased indomethacin dosing for persistent patent ductus arteriosus in preterm infants: a multicenter, randomized, controlled trial.
Ductus arteriosus ligation and alveolar growth in preterm baboons with a patent ductus arteriosus.
Risk factors for persistent ductus arteriosus patency during indomethacin treatment.
The effects of caffeine on the preterm sheep ductus arteriosus.
Calcium-dependent and calcium-sensitizing pathways in the mature and immature ductus arteriosus.
Patent ductus arteriosus: evidence for and against treatment.
Indomethacin prophylaxis for preterm infants: the impact of 2 multicentered randomized controlled trials on clinical practice.
Inhibition of cyclooxygenase isoforms in late- but not midgestation decreases contractility of the ductus arteriosus and prevents postnatal closure in mice.
Improved lung growth and function through hypoxia-inducible factor in primate chronic lung disease of prematurity.
Mechanisms regulating the ductus arteriosus.
Enhancement of angiogenic effectors through hypoxia-inducible factor in preterm primate lung in vivo.
Patent ductus arteriosus: pathophysiology and management.
Combined treatment with a nonselective nitric oxide synthase inhibitor (l-NMMA) and indomethacin increases ductus constriction in extremely premature newborns.
Postnatal constriction, ATP depletion, and cell death in the mature and immature ductus arteriosus.
Effect of ductus ligation on cardiopulmonary function in premature baboons.
Activation of hypoxia-inducible factors in hyperoxia through prolyl 4-hydroxylase blockade in cells and explants of primate lung.
ATP depletion and cell death in the neonatal lamb ductus arteriosus.
The role of monocyte-derived cells and inflammation in baboon ductus arteriosus remodeling.
Intracellular-specific colocalization of prostaglandin E2 synthases and cyclooxygenases in the brain.
Oxygen-saturation targets and outcomes in extremely preterm infants.
Developmental regulation of prostaglandin E2 synthase in porcine ductus arteriosus.
Effects of hypoxia, hypoglycemia, and muscle shortening on cell death in the sheep ductus arteriosus.
Vasa vasorum hypoperfusion is responsible for medial hypoxia and anatomic remodeling in the newborn lamb ductus arteriosus.
In utero indomethacin alters O2 delivery to the fetal ductus arteriosus: implications for postnatal patency.
Renal effects of cyclooxygenase-2 inhibition in fetal lambs.
VEGF regulates remodeling during permanent anatomic closure of the ductus arteriosus.
Prostanoid receptors: ontogeny and implications in vascular physiology.
Combined prostaglandin and nitric oxide inhibition produces anatomic remodeling and closure of the ductus arteriosus in the premature newborn baboon.
Factors that increase the contractile tone of the ductus arteriosus also regulate its anatomic remodeling.
Characterization of PGE2 receptors in fetal and newborn lamb ductus arteriosus.
Characterization of PGE2 receptors in fetal and newborn ductus arteriosus in the pig.
Ibuprofen and patent ductus arteriosus.
Tissue hypoxia inhibits prostaglandin and nitric oxide production and prevents ductus arteriosus reopening.
Cyclooxygenase-2 inhibitors constrict the fetal lamb ductus arteriosus both in vitro and in vivo.
Parental attitudes regarding interviews about injuries to their children.
Prophylactic indomethacin: factors determining permanent ductus arteriosus closure.
Incidence and outcome of a 10-fold indomethacin overdose in premature infants.
Cyclooxygenase-2 plays a significant role in regulating the tone of the fetal lamb ductus arteriosus.
Permanent anatomic closure of the ductus arteriosus in newborn baboons: the roles of postnatal constriction, hypoxia, and gestation.
Expression of cyclooxygenases in ductus arteriosus of fetal and newborn pigs.
Endothelin-receptor blockade does not alter closure of the ductus arteriosus.
Regulation of ductus arteriosus patency by nitric oxide in fetal lambs: the role of gestation, oxygen tension, and vasa vasorum.
Risk factors associated with infant death among very low birth weight infants after discharge from an intensive care nursery.
Imaging hypoxia and blood flow in normal tissues.
Recommendations for the postnatal use of indomethacin: an analysis of four separate treatment strategies.
Transforming growth factor-beta protein and messenger RNA expression is increased in the closing ductus arteriosus.
Factors determining reopening of the ductus arteriosus after successful clinical closure with indomethacin.
Transforming growth factor beta 1 inhibits fetal lamb ductus arteriosus smooth muscle cell migration.
Indomethacin as a tocolytic agent: the controversy continues.
Ductus arteriosus smooth muscle cell migration on collagen: dependence on laminin and its receptors.
Phospholipase C gamma activation, phosphotidylinositol hydrolysis, and calcium mobilization are not required for FGF receptor-mediated chemotaxis.
Neonatal complications after the administration of indomethacin for preterm labor.
Beta 1 and beta 3 integrins have different roles in the adhesion and migration of vascular smooth muscle cells on extracellular matrix.
Patent ductus arteriosus increases lung fluid filtration in preterm lambs.
Patent ductus arteriosus, indomethacin, and intestinal distension: effects on intestinal blood flow and oxygen consumption.
The integrin complex alpha v beta 3 participates in the adhesion of microvascular endothelial cells to fibronectin.
Persistent patent ductus arteriosus.
The effects of the patent ductus arteriosus on diaphragmatic blood flow and function.
Human microvascular endothelial cells use beta 1 and beta 3 integrin receptor complexes to attach to laminin.
Integrin receptors on aortic smooth muscle cells mediate adhesion to fibronectin, laminin, and collagen.
An alpha 1/beta 1-like integrin receptor on rat aortic smooth muscle cells mediates adhesion to laminin and collagen types I and IV.
Effect of medical and social risk factors on outcome of prematurity and very low birth weight.
The effect of methylprednisolone on hypoxic pulmonary vasoconstriction in the newborn late-gestation lamb.
Effect of patent ductus arteriosus on water accumulation and protein permeability in the lungs of mechanically ventilated premature lambs.
Bradykinin produces pulmonary vasodilation in fetal lambs: role of prostaglandin production.
Meclofenamate does not affect lung development in fetal sheep.
Influence of increased pulmonary vascular pressures on the closure of the ductus arteriosus in newborn lambs.
Meclofenamate increases ventilation in lambs.
Reactive oxygen metabolites relax the lamb ductus arteriosus by stimulating prostaglandin production.
Effects of prostaglandin D2 on pulmonary arterial pressure and oxygenation in newborn infants with persistent pulmonary hypertension.
Prostaglandin E2 causes hypoventilation and apnea in newborn lambs.
The role of beta-adrenoreceptor stimulation and contractile state in the preterm lamb's response to altered ductus arteriosus patency.
Effects of meclofenamate on breathing movements in fetal sheep before delivery.
Indomethacin and patent ductus arteriosus: effects on renal function in preterm lambs.
Lung vascular effects of lipid infusion in awake lambs.
Respiratory effects of a patent ductus arteriosus in premature newborn lambs.
How a patent ductus arteriosus effects the premature lamb's ability to handle additional volume loads.
Indomethacin therapy for patent ductus arteriosus: when is prophylaxis not prophylactic?
Cardiovascular effects of patent ductus arteriosus in preterm lambs with respiratory distress.
Piriprost: a putative leukotriene synthesis inhibitor increases pulmonary blood flow in fetal lambs.
Visual acuity development in normal and abnormal preterm human infants.
Ductus arteriosus: current theories of prenatal and postnatal regulation.
Effects of prostaglandins on fetal breathing do not involve peripheral chemoreceptors.
Regulation of breathing movements in fetal sheep by prostaglandin E2.
Thromboxane is not responsible for the high pulmonary vascular resistance in fetal lambs.
Effects of a protein-free, synthetic surfactant on survival and pulmonary function in preterm lambs.
Meclofenamate and prostaglandin E2 affect breathing movements independently of glucose concentrations in fetal sheep.
The role of the patent ductus arteriosus in respiratory distress syndrome.
Videophone use improves maternal interest in transported infants.
A comparison of continuous wave Doppler ultrasonography with microsphere measured left-to-right shunt through the patent ductus arteriosus.
Effect of gestational age on ductus arteriosus response to circulating prostaglandin E2.
Role of circulating prostaglandin E2 in regulation of the ductus arteriosus.
When to treat the patent ductus arteriosus with indomethacin in very-low-birth-weight infants.
Evaluation of alprostadil (prostaglandin E1) in the management of congenital heart disease in infancy.
Prophylactic indomethacin therapy for patent ductus arteriosus in very-low-birth-weight infants.
Ontogeny and regulation of corticosteroid binding globulin capacity in plasma of fetal and newborn lambs.
Increased shunt through the patent ductus arteriosus after surfactant replacement therapy.
Risk factor analysis of intraventricular hemorrhage in low-birth-weight infants.
Effects of antenatal glucocorticoid administration on ductus arteriosus of preterm lambs.
Pharmacology of the ductus arteriosus.
Glucocorticoids alter the sensitivity of the lamb ductus arteriosus to prostaglandin E2.
Prenatal administration of betamethasone for prevention of patient ductus arteriosus.
Circulating prostaglandin E2 concentrations and patent ductus arteriosus in fetal and neonatal lambs.
Does a belief in a 'just world' affect health care providers' reactions to perinatal illness?
Issues concerning parents after the death of their newborn.
Ontogeny of the ductus arteriosus response to prostaglandins and inhibitors of their synthesis.
Age-dependent sensitivity of the lamb ductus arteriosus to indomethacin and prostaglandins.
Ductus arteriosus: developmental response to endogenous prostaglandins, oxygen, and indomethacin.
Developmental response to indomethacin: a comparison of isometric tension with PGE2 formation in the lamb ductus arteriosus.
Formation of prostacyclin (PGI2) by the ductus arteriosus of fetal lambs at different stages of gestation.
Developmental responses to oxygen, arachidonic acid, and indomethacin in the fetal lamb ductus arteriosus in vitro.
PGE2 is a more potent vasodilator of the lamb ductus arteriosus than is either PGI2 or 6 keto PGF1alpha.
Agents that increase cyclic AMP inhibit accumulation of cGMP and depress human monocyte locomotion.
Patent ductus arteriosus: a new light on an old problem.
Responsiveness of the lamb ductus arteriosus to prostaglandins and their metabolites.
Regulation of Cyclic nucleotide metabolism in the human umbilical artery.
The developmental response of the ductus arteriosus to oxygen.
Oxygen tension and the response of the ductus arteriosus to PGE: searching high and low for a solution.
Ductus arteriosus responses to prostaglandin E1 at high and low oxygen concentrations.
Oxygen: influence on cyclic nucleotides and calcium sequestration in the human umbilical artery.
Calcium uptake by subcellular fractions of human umbilical artery.
Oxygen and cyclic nucleotides in human umbilical artery.
The role of calcium in regulation of cyclic nucleotide content in human umbilical artery.
Guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate content of human umbilical artery.
The effect of serotonin (5-hydroxytryptamine) and derivatives on guanosine 3',5'-monophosphate in human monocytes.
Nucleic acid deficiency in the prothanic homozygous mutant of creeper fowl.
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