Patent ductus arteriosus in neonates

Patency of the ductus arteriosus is one of the more common problems of the neonate. Although the ductus arteriosus usually closes within the first days of life, persistent patency can complicate the clinical status of a newborn. The ductus arteriosus also may play a role in the pathophysiology of persistent pulmonary hypertension of the newborn and in some forms of congenital heart disease. Diagnosis of patent ductus arteriosus can be suspected clinically but should be verified by echocardiography before treatment. Accurate diagnosis, early intervention and proper treatment are necessary to decrease the immediate risks and minimize the potential for long-term complications.     

Physiologic changes associated with ligation of the ductus arteriosus in preterm infants

Cardiorespiratory and transcutaneous oxygen monitors were used on 13 preterm neonates to examine physiologic changes during ductus arteriosus ligation. Transcutaneous oxygen decreased 30 seconds after left lung deflation; all infants required increases in inspired oxygen and ventilation to correct abnormal values after the left lung was compressed. Transcutaneous oxygen decreased 30 seconds after ductus arteriosus ligation (mean delta tcPO2 = -17 mm Hg +/- 11.4) but increased 150 seconds after left lung inflation (mean delta tcPO2 = 46.9 mm Hg +/- 28.8). Arterial blood pressure increased (mean delta systolic BP = 17.9 mm Hg +/- 9.5) and heart rate decreased 10 seconds after ductus arteriosus ligation. In five neonates, gradual closure of the ductus arteriosus over 40 to 75 seconds resulted in a more gradual increase in blood pressure. Intraventricular hemorrhage was confirmed in two patients after surgery. Ligation of the ductus arteriosus results in an abrupt increase in blood pressure, which may be related to the pathogenesis of intraventricular hemorrhage. We suggest that the ductus arteriosus be closed gradually to allow a more gradual increase in blood pressure.     

Ductus arteriosus dilatation by prostaglandin E1 in infants with pulmonary atresia

Infants with pulmonary atresia depend on patency of the ductus arteriosus for survival in the immediate postnatal period. Despite continuing hypoxemia after birth the ductus arteriosus usually constricts, thus reducing pulmonary blood flow. This often occurs while awaiting surgical palliation or correction, leading either to marked deterioration in the infant's condition, or death. In ten infants with pulmonary atresia, we infused prostaglandin E1 (PGE1) at a rate of 0.1 mug/kg/min in six and 0.05 mug/kg/min in four into the descending aorta at the orifice of the ductus arteriosus. The ductus arteriosus was effectively dilated; at the narrowest point the diameter, measured in eight infants, almost doubled. In all ten infants arterial blood PO2 increased, averaging 24.6 mm Hg before and 43.7 mm Hg after the infusion was started. Infusion of PGE1 directly into the aorta adjacent to the ductus arteriosus avoided the complications of pyrexia, muscular twitching, and excitability which may be related to the effects of prostaglandins on the central nervous system.     

Mechanisms of oxygen-induced contraction of ductus arteriosus isolated from the fetal rabbit

The present study was designed to investigate the effect of O2 on intracellular Ca concentration ([Ca]i) in the ductus arteriosus and the mechanisms for O2-induced ductal contraction. The force of isometric contraction of the ring of the ductus arteriosus isolated from fetal rabbits at 30 days of gestation (term, 31 days) was measured. The ductus arteriosus was loaded with fura 2, a calcium-sensitive dye, and [Ca]i was determined from the ratio of fluorescence intensity at 340 and 380 nm excitation wavelengths. The ductus arteriosus was initially superfused with hypoxic control solutions and contraction was induced by application of oxygenated solutions. The O2-induced contraction of the ductus arteriosus was associated with increases in [Ca]i and was eliminated in the absence of extracellular calcium. An increase in [K]o from 5 to 50 mM, which causes membrane depolarization, induced ductal contraction. The calcium channel blockers verapamil, diltiazem, and nickel caused a similar inhibition of O2-induced contraction as well as KCl-induced contraction. The role of intracellular calcium stores in O2-induced ductal contraction was examined using ryanodine, an inhibitor of calcium uptake and release from the sarcoplasmic reticulum. The inhibition of O2-induced contraction by ryanodine was minimal. Infusion of glibenclamide, an inhibitor for opening the ATP-sensitive potassium channel, caused contraction of the ductus arteriosus in the hypoxic solution. Cromakalim, an opener of ATP-sensitive potassium channels, completely relaxed the contraction induced by O2. These data suggest that O2 increases [Ca]i and causes contraction in the ductus arteriosus. Application of O2 may change from anaerobic to aerobic metabolism and depolarize membrane potential by closing the ATP-sensitive potassium channel, which in turn increases calcium influx via the voltage-dependent calcium channel. Mechanisms other than the ATP-sensitive potassium channel may also be involved in the O2-induced contraction and remain to be studied.     

Cerebral blood flow and EEG changes in preterm infants with patent ductus arteriosus

It is unknown whether the decreased cerebral blood flow seen in infants with a large patent ductus arteriosus is associated with cerebral dysfunction. Decreased cerebral blood flow in adult human and animal models has been associated with altered electroencephalography (EEG), spectral-analyzed EEG, and EEG response to photic stimulation. Cerebral blood flow velocity, EEG, spectral analysis of EEG, and photic alteration of EEG spectra were evaluated in 8 infants before and after closure of a significant patent ductus arteriosus and in 10 control infants without a patent ductus arteriosus. All infants with patent ductus arteriosus had moderate or large shunts associated with a 25% mean reduction in cerebral blood flow velocity. There were no differences, however, in EEG, spectral analysis of EEG, or photic alteration of the spectral analysis for these infants before and after patent ductus arteriosus closure as compared to controls. It is concluded that the degree of decreased cerebral blood flow in infants with a significant patent ductus arteriosus is not sufficient to cause measurable alteration in electrocortical activity.     

Transcatheter closure of patent ductus arteriosus in children and adults

AIM: To describe the initial New Zealand experience of transcatheter patent ductus arteriosus closure in adults and children. METHODS: Twenty-three children beyond infancy and four adults with isolated patent ductus arteriosus were selected for transcatheter umbrella closure. Rashkind umbrellas were placed across the patent ductus arteriosus through a percutaneously inserted long venous sheath using the Mullins technique. RESULTS: In 25 of the 27 patients a Rashkind umbrella was placed accurately. In two patients the umbrella could not be placed accurately: in one the procedure was abandoned uneventfully and in one the umbrella embolised to the right pulmonary artery necessitating surgical removal of the device and patent ductus arteriosus closure. There were no other significant complications. A second umbrella insertion is planned in two children for a significant residual leak at 1-year follow up. CONCLUSIONS: Transcatheter patent ductus arteriosus closure is a low risk and usually effective alternative to surgical closure for the majority of patients beyond infancy.     

A rare case of patent ductus arteriosus in a dog with glomerular mesangiolysis

Rare case of patent ductus arteriosus (PDA) was observed in a 2-year and 9 month-old Miniature Dachshund which had been diagnosed as severe cardiac failure. Pulmonary artery from the right ventricle connected to dilated ductus arteriosus, and pulmonary artery-ductus arteriosus-descending aorta formed a continuous duct, which seemed to be the main route of bloodstream. Ascending aorta from the left ventricle was hypoplastic, and connected to the dilated ductus arteriosus. Glomerular mesangiolysis due to heart failure was also observed in the kidney.     

Truncus arteriosus with patent ductus arteriosus and normal aortic arch

In hearts with a common arterial trunk (truncus arteriosus), there is almost always an inverse development of the aortic arch and the ductus arteriosus. Truncus with a normal aortic arch and a patent ductus is a rare echocardiographic and surgical finding. In this report, we describe 2 neonates in whom truncus arteriosus with a normal aortic arch and a medium or large patent ductus was diagnosed by preoperative echocardiography (without catheterization) and confirmed intraoperatively.     

Actions of growth hormone-release inhibiting hormone (somatostatin) on the renin aldosterone system

Contractile responses of rings of ductus arteriosus from fetal and neonatal guinea pigs were studied in buffered Krebs-Henseleit solutions of various oxygen tensions. Oxygen-induced contraction of ductus arteriosus increased with gestational age, peaking at term and attenuating within 24 h after birth. Contractions of ductus in response to potassium were not different in term and preterm fetuses. Maximal contractile response of pre- and postductal aortic rings to oxygen was 8.3% of the maximal oxygen-induced contraction of ductal rings from the same fetuses. Pulmonary artery was quite insensitive to oxygen. Of 12 ductus exposed to bradykinin in the absence of oxygen seven contracted (maximal response was obtained with 15.0 ng/ml). Exposure of ductus to bradykinin in the absence of oxygen enhanced subsequent contractions of ductal smooth muscle rings to air. Atropine failed to inhibit the oxygen-induced contraction of ductus. These data suggest that acetylcholine is not essential for oxygen-induced contraction of the guinea pig ductus arteriosus.     

Patch testing in children

Indomethacin is a very effective tocolytic agent. However, concern about its possible constrictive effect on fetal ductus arteriosus has limited the use of this medication in pregnancy. A 29-year-old woman was treated with indomethacin at 27 weeks of gestation for preterm labor and polyhydramnios. She received a dose of 75 mg/day for 5 weeks. At 35 weeks of gestation, she had a cesarean delivery due to fetal distress, and a hydropic baby was delivered. The infant died shortly after. Nonimmune hydrops fetalis and closed ductus arteriosus were the only pathological findings at autopsy. In utero, irreversible, complete closure of the ductus arteriosus is very rare. In the case presented, prolonged use of indomethacin during pregnancy was associated with complete closure of the ductus arteriosus that developed most probably after discontinuation of therapy. This case emphasizes the need for frequent fetal echocardiography examinations during as well as after maternal indomethacin treatment.     

Effectiveness of five-loop coils to occlude patent ductus arteriosus

Coil occlusion of patent ductus arteriosus with 5-loop coils was undertaken in 10 patients without coil embolizations, and with 90% immediate occlusion and 100% occlusion at follow-up. We conclude that 5-loop coil occlusion of patent ductus arteriosus is safe and effective.     

Aneurysm of the nonpatent ductus arteriosus in the adult--a report of the case and review of the literature

Aneurysm of the ductus arterious in adult in rare. 28 cases have been previously reported in the Japanese literature. A new 73-year-old male case, preoperatively diagnosed and successfully repaired, are presented. The patient with hoarseness was admitted to our hospital. Contrast-enhanced CT scans and aortograms made a diagnosis for the aneurysm of the ductus arteriosus. Operation was done through left thoracotomy with the aid of partial cardiopulmonary bypass. The pulmonary arterial end of the ductus arteriosus was closed and a Ligamentum arteriosus was identified. A 3 by 2.7 cm saccular aneurysm was resected and segmental replacement of the aorta with woven dacron graft was performed. Because of it's critical location and the high incidence of complications, aneurysm of the ductus arteriosus in the adult should be surgically corrected when diagnosed.     

Debt and career choices of underrepresented minorities

We report a case of right aortic arch with mirror-image branching and coarctation of the aorta and left ductus arteriosus in a 6-year-old boy. He was referred to Chang Gung Children's Hospital with suspected left ventricular failure. Physical examination revealed hypertension and a pulse discrepancy between the upper and lower extremities. Echocardiography and magnetic resonance imaging revealed a right aortic arch, a long segmental aortic coarctation, and a patent ductus arteriosus. In addition, mirror-image branching of the brachiocephalic vessels was found. The coarctation was resected and the ductus arteriosus was ligated. The postoperative recovery was uneventful and the blood pressure returned to normal. He remained normotensive and had no symptoms of heart failure within the 2 years of follow-up.     

Coil on the loop and selectively enhanced stiffness for improved control: feasibility study in the neonatal ovine model of the large patent ductus arteriosus

RATIONALE AND OBJECTIVES: Several devices have been suggested and tested for interventional closure of the persistent ductus arteriosus. Coils were found effective only in small ducts due to their lack of maneuverability and physical limitation of grip forces leading to risk of embolization. The authors evaluated the feasibility to place single coils with selectively enhanced stiffness into high shunting ductus arteriosus, the coils being deployed and controlled through a veno-arterial loop in a bovine model. METHODS: "Double-cone" shaped, stainless steel coils with enhanced stiffness of the outer rings were mounted on either end on a nitinol core wire. A snap-in mechanism attaches the coil to this delivery wire and is freed by a pusher system of coiled steel wire that is advanced over the core wire. Forming a veno-arterial loop across the patent ductus allows for repositioning into the pulmonary artery or aortic catheter. A chronic lamb model of large patent ductus arteriosus (PDAs) (> or = 9 mm) was used in which ductus patency was secured by a protocol of repetitive angioplasties. Different systems (n = 10) were placed having retrieved the previous coil by a snare after definitive release. RESULTS: Placement of coils was possible in all 10 attempts. The coils were pulled back into the catheters between five and eight times before definitive release. CONCLUSIONS: The device allows controlled placement of single coils in our model of large PDAs and may lead the way to overcome previous limitations of coils. Clinical trials are warranted.     

Gene transfer in utero biologically engineers a patent ductus arteriosus in lambs by arresting fibronectin-dependent neointimal formation

Closure of the ductus arteriosus requires prenatal formation of intimal cushions, which occlude the vessel lumen at birth. Survival of newborns with severe congenital heart defects, however, depends on ductal patency. We used a gene transfer approach to create a patent ductus arteriosus by targeting the fibronectin-dependent smooth muscle cell migration required for intimal cushion formation. Fetal lamb ductus arteriosus was transfected in utero with hemagglutinating virus of Japan liposomes containing plasmid encoding 'decoy' RNA to sequester the fibronectin mRNA binding protein. Fibronectin translation was inhibited and intimal cushion formation was prevented. We thus established the essential role of fibronectin-dependent smooth muscle cell migration in intimal cushion formation in the intact animal and the feasibility of incorporating biological engineering in the management of congenital heart disease.     

Effect of antenatal administration of thyrotrophin releasing hormone on fetal flow velocity waveforms

AIM: To determine whether antenatal administration of thyrotrophin releasing hormone (TRH), to promote lung maturation, alters blood flow through the fetal middle cerebral, umbilical artery, or ductus arteriosus and through the maternal uterine arteries. METHODS: The effect of transplacentally administered TRH on the fetal circulation was prospectively evaluated in 30 patients between 24 and 34 weeks' gestation. TRH (400 micrograms) was given to the mother intravenously either as a bolus or an infusion. Fetal effects were determined by measuring the maximum velocity and pulsatility index (PI) in middle cerebral artery, ductus arteriosus, uterine artery and umbilical artery Doppler waveforms. Measurements were made immediately before, and 10 and 60 minutes after maternal TRH administration. RESULTS: Intravenous injection of TRH had no significant effect on PI in the uterine, umbilical, or middle cerebral artery and the ductus arteriosus within 60 minutes of administration in either group. CONCLUSION: The antenatal use of TRH in conjunction with steroids for fetal lung maturity does not affect utero-placental or fetal haemodynamic variables, as measured by Doppler. These findings, therefore, do not support the suggestion that antenatal intravenous administration of TRH either as bolus or infusion may have immediate adverse vascular effects in the fetus.     

Personal constitution and health status among Chinese elderly in Taipei and Los Angeles

Ligation of the ductus arteriosus in utero produces fetal and neonatal pulmonary hypertension and alterations in the hemodynamic responses to nitric oxide and endothelin-1 in fetal and newborn lambs. To determine whether fetal pulmonary hypertension alters the expression of the genes of the nitric oxide and endothelin-1 pathways, seven fetal lambs (123-126-d gestation) underwent ligation of the ductus arteriosus. Near-term (138-139-d gestation), total lung RNA, and protein were prepared from control and ductal ligation fetal lambs for RNase protection assays and Western blotting. Ligation of the ductus arteriosus was associated with decreased expression of endothelial nitric oxide synthase mRNA and protein, and the alpha1 and the beta1 subunits of soluble guanylate cyclase protein; and with increased expression of phosphodiesterase V mRNA. Ligation of the ductus arteriosus was also associated with increased expression of preproendothelin-1 mRNA and with decreased expression of endothelin B receptor (ET(B)) mRNA. These results suggest that there is coordinated regulation of genes of the nitric oxide pathway, which would decrease nitric oxide and cGMP concentration, thereby decreasing pulmonary vasodilator activity. There is also coordinated regulation of genes of the endothelin-1 pathway, which would increase endothelin-1 concentration and limit ET(B) receptor activation, thereby increasing pulmonary vasoconstrictor activity. These alterations in gene expression would increase fetal pulmonary vascular resistance, contributing to the development of pulmonary hypertension after birth.     

Controllable graded cerebral ischaemia in the gerbil: studies of cerebral blood flow and energy metabolism by hydrogen clearance and 31P NMR spectroscopy

Patent ductus arteriosus is an uncommon anomaly in adult patients. Surgical closure of patent ductus arteriosus in this age group presents difficult problems to the surgeon. We report our experience of 21 adult patients (19-62 years of age, mean 40 years) who underwent closure of the ductus by transfemoral implantation of a Rashkind double umbrella device. The patients came to light because of atrial fibrillation, congestive heart failure, residual flow after surgical ligation of the duct or because of incidental diagnosis made during physical examination or chest X-ray. In ten patients the pulmonary arterial pressure was normal (systolic pressure < 30 mmHg), in eleven it was elevated (systolic pressure from 30 to 100 mmHg, mean 50 mmHg). In seven patients the duct was clearly calcified and the size of the duct varied from 3 to 9 mm (mean 4.3 mm). In 16 patients the ductus resulted perfectly closed after implantation of the first double umbrella device, two patients had minimal residual aortopulmonary flow, whereas in three patients the residual shunt was significant; two of these also developed haemolysis and went to surgery, in the latter the shunt was completely abolished after implantation of a second 17-mm device 16 months later. In conclusion transcatheter closure of patent ductus arteriosus in adults is feasible, even in the presence of calcifications and/or pulmonary hypertension; taking into account the significant surgical risk, PDA umbrella closure should be considered the first choice procedure in this group of patients.     

The large window ductus: a surgical trap

A rare window type of patent ductus arteriosus is reported that was large (15 mm in maximal transverse dimension) but had virtually no length and hence was externally invisible. The smaller aortic isthmus (4 mm in diameter), which was intrapericardial, was mistaken for the ductus and was inadvertently clip-occluded, leading to death. After a specific diagnosis is made, the large window ductus should be patched on cardiopulmonary bypass with a transpulmonary approach.