[Hemodynamics in patent ductus arteriosus with pulmonary hypertension--with special reference to a case without heart murmurs due to patent ductus arteriosus].
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The vasoactivity of the fetal lamb ductus arteriosus studied in utero.
The ductus arteriosus of the undisturbed fetal lamb was studied chronically by techniques that allowed direct serial measurements of the calibre of the fetal channel. When the direct actions were studied of vasoactive agents on the ductus arteriosus, prostaglandins did not dilate the vessel beyond its resting dimensions. The cyclooxygenase inhibitor, indomethacin, was a potent vasoconstrictor with a plateau of the dose-effect relationship occurring at 0.2 mg/kg. Fetuses of 95--98 days gestational age were equally sensitive to indomethacin when compared to animals near term. Although the prostaglandins, PGE1, PGE2 PGF2 alpha, PGH2, PGI2 and PGG2, had no direct effect on the ductus arteriosus, PGE1, PGE2, PGH2 and PGI2 reversed the vasoconstrictor action of indomethacin. Autonomic nervous system mediators and blockers, i.e., acetylcholine, atropine, norepinephrine, propranolol, phentolamine and methoxamine, had neither direct effects on the ductus arteriosus nor any influence of indomethacin-induced vasoconstriction. The same was true of angiotensin 1, angiotensin 2, blockade of conversion of angiotensin 1 to 2, serotonin, methysergide, aminophylline, adenosine, and dibutyryl cyclic AMP. Imidazole, a blocker of thromboxane synthase, had no direct effect on the ductus arteriosus, but reduced significantly the magnitude of the indomethacin constrictor action. The major finding of this investigation was the exquisite sensitivity of the ductus arteriosus to manipulations of the prostaglandin environment. The results suggest that both locally generated prostaglandins, as well as prostanoids in the circulation, may be involved in ductal patency and closure. A high degree of control is likely of the circulation of the ductus arteriosus and constriction of the fetal channel is probably the result of an active process.
Adenosine↗
Role of the vagus nerve and its recurrent laryngeal branch in the development of the human ductus arteriosus.
The reason that the normal ductus arteriosus has a muscular media, contrasting with the elastic lamellar structure of the adjacent great arteries, is unknown. We examined the hypothesis that the anatomic relationship of the ductus arteriosus to the vagus and recurrent laryngeal nerves during early development might be of importance in influencing ductal morphology. Normal human embryos from the Carnegie Embryological Collection and embryos and fetuses from the Hopkins Pathology Collection were studied microscopically, by reconstructions made from serial histologic sections, or by gross dissection. At Carnegie stage 16 the recurrent laryngeal nerves pass medially from the vagus nerve to the laryngeal area and are caudal to the bilaterally symmetric sixth aortic arches. By stage 18 the right sixth aortic arch has disappeared and the left sixth aortic arch is in a more caudal position relative to the larynx. The left vagus nerve and its recurrent laryngeal branch form a sling supporting the distal (or ductus arteriosus component) of the left sixth aortic arch. In subsequent development there is greater relative separation of the larynx and ductus arteriosus. The media of the ductus arteriosus beneath the supporting nerves is thinner and has less elastic fiber formation than the elastic lamellar media of the adjacent aortic arches. The study shows that the vagus and recurrent laryngeal nerves are in a position to provide mechanical support to the ductus arteriosus during its development and that the morphology of the media of the supported ductus arteriosus differs from that of the adjacent unsupported aortic arches. It is suggested that this local mechanical support may be the reason that the normal ductus arteriosus differentiates as a muscular artery and is therefore able to obliterate its lumen in postnatal life. Without such support the ductal media could develop the abundant elastic fibers characteristic of the normal unsupported aorta and pulmonary trunk and become an abnormal, persistently patent ductus arteriosus.
Ductus Arteriosus↗
Fetal and transient neonatal right heart dilatation with severe tricuspid valve insufficiency in association with abnormally S-shaped kinking of the ductus arteriosus.
Alterations of the ductus arteriosus, e.g. occlusion, constriction or aneurysm, can influence the fetal and neonatal circulation. A case of fetal right atrial and ventricular dilatation, severe tricuspid valve insufficiency and transient pulmonary valve regurgitation at 32 weeks of gestation is reported. Structural heart defects and extracardiac diseases (e.g. high output cardiac failure in arteriovenous shunts and anemia) were excluded by Doppler echocardiography and fetal blood sampling. An abnormally S-shaped kinking of the ductus arteriosus with increased systolic and diastolic flow velocities in the distal part was demonstrated. At 35 weeks' gestation, Cesarean section was performed, because of increased tricuspid valve insufficiency, and a healthy boy was born. After birth, right heart dilatation and tricuspid valve insufficiency decreased. The cardiac changes in relation to the anatomical abnormality of the ductus arteriosus are discussed.
Adult↗
Current therapy of the patent ductus arteriosus.
The patent ductus arteriosus (PDA) was the first congenital heart lesion to be treated surgically and also the first to be treated with nonsurgical catheter intervention. Surgical ligation and division of the ductus remains the gold standard for consistently achieving complete occlusion. Transaxillary muscle-sparing thoracotomy and video-assisted thoracoscopic ligation, however, have evolved as surgical alternatives with reduced trauma, shorter hospitalization, and excellent cosmetic result but are associated with a significant rate of residual or recurrent duct patency. With aggressive application of critical pathway methods, significant reduction in cost has been achieved for surgical PDA closure. Nonsurgical transcatheter closure nevertheless has gained widespread acceptance, mostly employing detachable or nondetachable stainless steel coils. Coils have superseded the previously popular Rashkind PDA occluder (USCI/Bard, Tewksbury, MA) because of significantly lower cost, less cumbersome handling, smaller delivery catheters, and superior occlusion rates. Various coil implantation techniques and detachment mechanisms have been devised. Large PDAs with smallest diameter greater than 5 mm, however, still are better treated surgically until appropriate devices become available.
Age Factors↗
Transfemoral plug closure of patent ductus arteriosus.
A patent ductus arteriosus should be closed because of its hemodynamic significance and/or the risk of infective endocarditis. Mortality of surgery is low. In adults, however, technical problems can arise due to calcification of the ductus walls. Using the transfemoral plug technique, developed by Porstmann, we attempted a ductus closure without surgery on 35 patients. The youngest was an 11-year-old girl, the oldest a 63-year-old woman (mean age of all patients: 37 years). The pressure in the pulmonary artery ranged from 15/5 to 70/27 mmHg, the diameter of the ductus from 2 to 9 mm (mean: 4.4 mm). According to the size and shape of the ductus, a plug of polyvinyl alcohol (Ivalon) with an inner steel wire frame was prepared. Threaded over a long arterio-transductal venous track wire, the plug was introduced into the femoral artery and advanced into the ductus by a pushing catheter. After removal of the track wire the plug remained wedged in the ductus. In all 35 patients, transfemoral ductus closure was possible. Patients with complaints improved remarkably within some days. Heart size and pulmonary congestion decreased considerably. All patients were followed for a period of 1-46 months. In two of them, the ivalon plug embolized into a side branch of the left pulmonary artery 7 and 2 weeks after the procedure, but without serious consequences.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Redox control of oxygen sensing in the rabbit ductus arteriosus.
How the ductus arteriosus (DA) closes at birth remains unclear. Inhibition of O2-sensitive K+ channels may initiate the closure but the sensor mechanism is unknown. We hypothesized that changes in endogenous H2O2 could act as this sensor. Using chemiluminescence measurements with luminol (50 [mu]M) or lucigenin (5 [mu]M) we showed significantly higher levels of reactive O2 species in normoxic, compared to hypoxic DA. This increase in chemiluminescence was completely reversed by catalase (1200 U ml-1). Prolonged normoxia caused a significant decrease in K+ current density and depolarization of membrane potential in single fetal DA smooth muscle cells. Removal of endogenous H2O2 with intracellular catalase (200 U ml-1) increased normoxic whole-cell K+ currents (IK) and hyperpolarized membrane potential while intracellular H2O2 (100 nM) and extracellular t-butyl H2O2 (100 [mu]M) decreased IK and depolarized membrane potential. More rapid metabolism of O2- with superoxide dismutase (100 U ml-1) had no significant effect on normoxic K+ currents. N-Mercaptopropionylglycine (NMPG), duroquinone and dithiothreitol all dilated normoxic-constricted DA rings, while the oxidizing agent 5,5'-dithiobis-(2-nitrobenzoic acid) constricted hypoxia-dilated rings. NMPG also increased IK. We conclude that increased H2O2 levels, associated with a cytosolic redox shift at birth, signal K+ channel inhibition and DA constriction.
Animals↗
Skin reflectance changes in preterm infants with patent ductus arteriosus.
INTRODUCTION: Patent ductus arteriosus (PDA) is a common complication in preterm infants. While two-dimensional echocardiography is the method of choice for diagnosing a PDA, clinical signs are known to be of limited value. STUDY DESIGN: Haemodynamically significant PDA (hs-PDA) was defined as a ductal left-to-right shunt with elevated left atrial/aortic root ratio ( > 1.6:1), a ductal diameter > 2 mm, retrograde diastolic flow exceeding 30% of the anterograde flow and anterograde peak diastolic flow velocity in left pulmonary artery > 50 cm/s. A hs-PDA may affect the cerebral circulation and skin color is known to be related to local perfusion. In this study, we tested the value of a caudal-to-cephalic skin reflectance differential in detecting preterm infants with hs-PDA. The study was blinded and prospective. SUBJECTS: Fifteen infants with a hs-PDA (M: 8, F: 7; gestational age: 28.0 +/- 2.0 weeks, birth weight: 880 +/- 130 g) and 15 gender- and gestational age-matched infants without a haemodynamically significant PDA (M: 8, F: 7; gestational age: 28.2 +/- 2.3 weeks, birth weight: 885 +/- 135 g) participated to the study. OUTCOME MEASURE: Skin reflectance measurements were performed using a reflectance spectrophotometer (CM-2600d/2500d, Minolta, Osaka, Japan). Sole ("postductal" site) to forehead ("preductal" site) skin reflectance ratio (caudal-to-cephalic ratio). RESULTS: hs-PDA infants showed significantly lower forehead light reflectance values on for the whole visible spectrum (p < or = 0.043) with the exception of 580-590 nm (p = 0.058), whereas no statistically significant differences were observed for the sole skin reflectance between the two groups in the examined visible spectrum. Consequently, hs-PDA infants showed a significantly higher caudal to cephalic ratio in the 410-430 nm (p < or = 0.042), 460-530 nm (p < or = 0.027) and 590-700 nm (p < or = 0.011) wavelength ranges. CONCLUSIONS: These findings may provide a previously unrecognised clinical marker for haemodynamically significant PDA in preterm infants, thus predicting those preterm infants who may require intervention for PDA.
Blood Flow Velocity↗
A developmentally regulated program restricting insolubilization of elastin and formation of laminae in the fetal lamb ductus arteriosus.
BACKGROUND: The ductus arteriosus (DA) is a fetal vessel in which the elastic laminae fail to assemble normally in late gestation. This feature is associated with the development of intimal cushions, structures that partially occlude the DA lumen and assure that the vessel will close completely when it constricts postnatally. EXPERIMENTAL DESIGN: We studied the fetal lamb DA at two different gestational time-points, 100 days before, and 138 days coincident with intimal cushion formation (term = 145 days) to establish the ultrastructural basis for the 'disassembly' of elastic laminae apparent on light microscopy and to determine further whether the mechanism was due to increased elastolytic activity, decreased synthesis of tropoelastin, or impaired insolubilization of tropoelastin. RESULTS: Morphometric ultrastructural analyses of tissue from the 138-day gestation fetal lambs revealed that the volume density of elastin in the DA vessel wall was only 40% of that in the aorta (Ao) and 50% of that in the pulmonary artery (PA). Moreover, only 16% of the elastin present contributed to the formation of laminae when compared to 80% in the Ao and 50% in the PA. Despite the morphologic appearance of 'fragmented' elastin, there was no evidence of increased elastolytic activity in the DA at either gestational time-point as judged by solubilization of a [3H] elastin substrate. The reduced elastin apparent was morphologically accompanied by an increase in soluble (tropo) elastin in DA compared with Ao and PA, as measured by enzyme linked immunosorbent assay, in tissue from both 100- and 138-day gestation lambs. Lack of differences in tropoelastin mRNA levels when comparing the 3 vessels suggested that the enzyme linked immunosorbent assay measurements reflected increased DA tropoelastin accumulation owing to lack of insolubilization rather than an increase in synthesis. Reduced insolubilization of newly synthesized elastin was evident in the DA compared with the Ao at 100 days gestation and in the DA compared with both Ao and PA at 138 days gestation in association with reduced desmosine levels. CONCLUSIONS: The mechanism of the decrease in tropoelastin insolubilization was unrelated to lysyl oxidase activity in the tissue and represents a unique developmental program.
Animals↗
Magnetic resonance imaging of ductus arteriosus Botalli apertus in adulthood.
Ductus arteriosus Botalli apertus is a congenital cardiovascular malformation usually diagnosed in childhood by echocardiography and/or cardiac catheterization. Reports about magnetic resonance imaging of ductus arteriosus Botalli apertus are rare. We report about three adult female patients and one adult male patient in whom magnetic resonance imaging was able to demonstrate the pathology. In all four patients quantitative data about right ventricular function were calculated. Pulmonary hypertension with Eisenmenger syndrome detected by cardiac catheterization had developed in three of the four patients excluding operative closure of the ductus. The patient in whom pulmonary hypertension had not developed underwent successful operative closure of the ductus. Magnetic resonance imaging is a non-invasive tool that can be used for diagnosis of ductus arteriosus Botalli apertus and it allows to quantify right ventricular function. Magnetic resonance imaging can be used repetitively in patients with Eisenmenger syndrome which may be helpful for better timing of combined heart-lung transplantation as ultimate therapeutic strategy because deterioration of right ventricular function can be monitored.
Adult↗
[Intravascular hemolysis following percutaneous occlusion of the ductus arteriosus].
Transcatheter occlusion of patent ductus arteriosus has become a safe and successful technique, but it's not free of complications. We present the case of a two-year-old boy who underwent routine transcatheter closure of his patent ductus arteriosus, using a "coil" device. Twenty hours later he developed severe persistent hemolysis in association with residual ductal flow. Patient's clinical situation became stable when the device was removed. Pulmonary embolization of the device and hemolysis are the main complications of percutaneous closure of the patent ductus arteriosus. Hemolysis occurs rarely (0.5%) and is always associated with the presence of residual ductal flow. Several approaches to this problem have been described. Mild cases may require no intervention; however, when severe hemolysis is present, removal of the device may be needed, proceeding with surgical repair of the patent ductus arteriosus.
Catheter Ablation↗
Gentamicin pharmacokinetics in neonates with patent ductus arteriosus.
OBJECTIVES: To determine the effect of patent ductus arteriosus on the pharmacokinetics of gentamicin in neonates and to examine whether any particular pharmacokinetic parameter is of value as a marker of patent ductus arteriosus. DESIGN: Cohort study of neonates treated with gentamicin, according to a standard dosing protocol. SETTING: A 24-bed, Level III, neonatal intensive care unit. PATIENTS: Neonates treated with gentamicin at the time of admission to the neonatal intensive care unit, using a standard protocol, and who were < 36 wks of gestational age. INTERVENTIONS: All patients received a gentamicin loading dose, and had gentamicin concentrations measured at 2 and 12 hrs after this dose, in order to determine pharmacokinetic parameters and calculate the optimum maintenance dose. Those neonates subsequently diagnosed to have patent ductus arteriosus, based on clinical suspicion and echocardiographic confirmation, were compared with those neonates without clinically suspected patent ductus arteriosus. Gentamicin pharmacokinetic parameters were calculated using a one-compartment model. MEASUREMENTS AND MAIN RESULTS: A total of 322 courses of gentamicin were administered (patent ductus arteriosus, n = 106; control, n = 216). Gentamicin clearance was decreased in the patent ductus arteriosus group vs. the control group (40.02 vs. 44.73 mL/kg/hr; p < .0108). Volume of distribution was greater for patent ductus arteriosus patients (0.61 L/kg) than for controls (0.54 L/kg) (p < .0002). Also, volume of distribution was a useful marker for presence of patent ductus arteriosus, with a 92% specificity for patent ductus arteriosus. CONCLUSIONS: Gentamicin dosing should be altered in neonates with patent ductus arteriosus to reflect the impact of higher volume of distribution and lower clearance. When the gentamicin volume of distribution exceeds 0.7 L/kg, it may be of predictive value for the presence of patent ductus arteriosus.
Anti-Bacterial Agents↗
Prevalence of additional cardiovascular anomalies in patients referred for transcatheter closure of patent ductus arteriosus.
Catheter closure of the patent ductus arteriosus is now a reality. The purpose of this study was to establish the prevalence of associated cardiovascular defects and the accuracy of echocardiography in patients referred for transvenous ductal closure. This study reviewed 146 patients seen from 1981 to 1988: 126 with only a patent ductus arteriosus (Group I) and 20 with additional cardiovascular anomalies (Group II). Groups I and II did not differ significantly in age, gender or physical examination except for the presence of a continuous murmur (Group I 100% versus Group II 80%, p less than 0.001). A left patent ductus arteriosus was visualized by two-dimensional echocardiography in 96% of patients and was evident by Doppler study in 100%. A patent ductus arteriosus was not seen in six patients including a patient who was found to have only a collateral network from the aorta to the main pulmonary artery. The 12 patients with noncardiovascular abnormalities such as Down's syndrome were more likely than the overall group to have additional cardiovascular anomalies (6 of 12, p = 0.001). The cardiovascular anomalies encountered were varied. Eight of the 20 patients with such anomalies had only a restrictive ventricular septal defect in addition to the patent ductus arteriosus. Significant anomalies found at catheterization included two thoracic arteriovenous malformations and an isolated right carotid artery draining into the right pulmonary artery by way of a right ductus arteriosus. This study indicates that echocardiography is an effective diagnostic technique in this patient group. A thorough cardiac catheterization with angiography should be performed before implantation of a ductal device.
Child, Preschool↗
Patent ductus arteriosus in the preterm infant.
The ductus arteriosus is a communication between the main pulmonary trunk and the descending aorta. In utero, the ductus arteriosus allows blood flow to be diverted from the high-resistance pulmonary circulation to the descending aorta and the low-resistance placental bed. Functional closure of the ductus arteriosus occurs soon after birth but can be delayed in premature infants and in certain situations. Patency of the ductus arteriosus results in alterations in blood flow to many different organ systems. This article describes the physiologic effects, as well as symptoms, diagnosis, and management of a patent ductus arteriosus in the preterm infant.
Cyclooxygenase Inhibitors↗
Nitric oxide mediates LC-3-dependent regulation of fibronectin in ductus arteriosus intimal cushion formation.
Ductus arteriosus intimal cushion formation is characterized by fibronectin-dependent smooth muscle cell (SMC) migration. Enhanced fibronectin synthesis in ductus SMC is regulated by the interaction of LC-3, a microtubule-associated protein, with an AU-rich element (ARE) in the 3'-untranslated region of fibronectin mRNA, facilitating its recruitment to polyribosomes for translation. Since nitric oxide (NO) is implicated in posttranscriptional gene regulation and is produced in the ductus, we investigated its mechanistic role in LC-3-mediated fibronectin synthesis. NO production was sevenfold higher in ductus vs. aortic SMC (P<0.005) associated with increased neuronal NO synthase (nNOS) expression. The NOS inhibitor L-NMMA decreased fibronectin synthesis by approximately 45-50% (P<0.05), whereas the NO donor, SNAP, increased ductus fibronectin synthesis approximately onefold (P<0.05); neither agent altered fibronectin mRNA levels. Immunoblotting revealed that SNAP increased and L-NMMA reduced a membrane-associated phosphorylated form of LC-3. RNA gel mobility shift assays confirmed that NO enhanced LC-3 binding to the fibronectin mRNA ARE. Our studies indicate a tissue-specific program in the ductus arteriosus whereby elevated nNOS expression and NO production regulate the posttranscriptional increase in fibronectin synthesis required for SMC motility.
3' Untranslated Regions↗
Idiopathic constriction of the fetal ductus arteriosus.
Constriction of the ductus arteriosus in the fetus is well studied, but mostly secondary to maternal exposure to indomethacin or other non-steroidal anti-inflammatory medications, or structural cardiac lesions. We present a case of a fetus presenting with right ventricular hypertrophy secondary to an S-shaped ductus arteriosus with distal constriction diagnosed by pulsed Doppler imaging. A review of the recent English literature of similar cases is presented.
Adult↗
Etiology of patent ductus arteriosus in dogs.
Patent ductus arteriosus (PDA) is the most common congenital heart disease in dogs and usually causes heart failure and death unless corrected at a young age. Previous histologic studies in a line of dogs derived from Miniature Poodles with hereditary PDA identified varying degrees of hypoplasia and asymmetry of ductus-specific smooth muscle and the presence of aortalike elastic tissue in the ductus wall sufficient to cause patency. To determine if similar structural abnormalities cause PDA in other dogs, serial-section, 3-dimensional histology of ductal architecture was studied in 8 non-Poodle purebred dogs with PDA with no immediate family history of PDA. Morphologic abnormalities were observed in 7 of 8 dogs with PDA and essentially were the same as those in dogs known to have a hereditary form of PDA. These findings suggest that apparently sporadic PDA in these breeds is caused by a genetic defect in the structure of the ductus arteriosus that is similar or identical to that in the Poodle. The relatives of dogs with PDA, particularly parents, offspring, and siblings, should be screened for evidence of PDA. Dogs with PDA should not be used for breeding, regardless of breed.
Animals↗
Transfemoral closure of patent ductus arteriosus in adult patients.
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.
Adult↗