Fetal cardiovascular function during prolonged magnesium sulfate tocolysis.

The purpose of this study was to evaluate the fetal cardiovascular function during prolonged magnesium sulfate tocolysis. We performed a fetal ultrasonographic examination in 15 patients (Mg group) during magnesium sulfate tocolysis for the treatment of preterm labor. The maternal serum magnesium concentration was 5.7 +/- 0.5 mg/dl at the time of the examination. Sixteen fetuses in normal pregnancies at similar gestational ages were used as the control group. The fetal heart rate and the middle cerebral artery pulsatility index in the Mg group were lower than in the control group (p < 0.01). Fractional shortening (FS) of the right ventricle in the Mg group was lower (p < 0.01), while FS of the left ventricle was higher (p < 0.01) than in the controls. The calculated blood flow through the tricuspid orifice in the Mg group was lower than in the control group (p < 0.01). In contrast, the blood flow through the mitral orifice in the Mg group was higher than in the control group (p < 0.01). In conclusion, in spite of the fact that the right ventricular function is depressed, the fetus maintains its cardiac output during prolonged hypermagnesemia by increasing its left ventricular function. These results indicate the different fetal intracardiac and peripheral circulation, especially in the brain, from normal fetuses.

[Ventricular outflow tract obstruction by cardiac tumors during ACTH therapy of an infant with tuberous sclerosis].

In an infant with tuberous sclerosis and West syndrome, ACTH treatment was interrupted because of augmentation of the biventricular outflow tract obstruction. A 5-month-old boy, who had been diagnosed to have multiple cardiac tumors since in utero, manifested West syndrome with typical hypsarhythmia in EEG. Several days after starting low dose ACTH treatment, a systolic murmur due to biventricular outflow tract obstruction intensified with ventricular arrhythmia. A tumor in the left ventricular outflow tract was enlarged. Discontinuation of daily administration of ACTH and administration of a beta-blocking agent improved the cardiac problems. Acceleration of blood velocity in the outflow tracts disappeared two months later. Intracardiac morphology and hemodynamic performance should be monitored to avoid critical complications during ACTH treatment in patients with tuberous sclerosis.

Echocardiographic findings of pulmonary atresia or critical pulmonary stenosis and intact ventricular septum in utero.

BACKGROUND: Neonates with right ventricular outflow obstruction and intact ventricular septum show serious hemodynamic problems, such as severe hypoxemia, congestive heart failure due to massive tricuspid regurgitation, respiratory distress related to huge pulmonary hypoplasia or ventricular dysfunction due to right ventricle-coronary communication. Recent advances in fetal diagnosis include many cases of in utero diagnosis of pulmonary atresia or critical pulmonary stenosis and intact ventricular septum. METHOD: Among the fetuses examined from April 1994 to March 1998, five fetuses were found with pulmonary atresia (PA) or critical pulmonary stenosis (CPS). Fetal echocardiograms were reviewed to elucidate the accuracy of fetal information and the efficacy of fetal diagnosis in the perinatal management of patient with CPS or PA and intact ventricular septum. RESULTS: The five cases were divided into two groups: two with a very small right ventricle (group 1) and three with a tripartite right ventricle (group 2). Fetal cardiomegaly and right atrial dilatation were prominent in group 2, whereas cardiac sizes were normal in group 1. Serial fetal examination in one group 2 fetus revealed developing right ventricular hypertrophy in utero. All group 2 cases showed massive tricuspid regurgitation (TR). Estimated right ventricular pressures from TR always exceeded the systemic blood pressures of gestational age-matched neonates. Reversed flow through the ductus arteriosus was recorded in both groups and ductus-dependent pulmonary circulation after birth was anticipated. Patency of both tricuspid and pulmonary valves was difficult to recognize in utero, as was right ventricle-coronary artery communication. Four of the five cases were maternally transported and survived palliative and/or definitive intervention. One fetus with chromosomal abnormality was observed without intervention during infancy and received palliative surgery when she was two years old. CONCLUSION: Fetal hemodynamic information was useful for making decisions not only after birth, but also in utero, and may eventually result in improving the prognosis of babies with PA/CPS. Serial observation of the fetuses with PA/CPS may also suggest the possible pathogenesis of PA/CPS in utero.

Screening for QT prolongation using a new exponential formula.

We prospectively screened 14,227 school-aged children for evidence of QT prolongation using a exponential formula (eQTc = (QT interval)/(RR interval)0.31) and criteria (ie: abnormal eQTc was defined as being equal to or greater than 0.430 and 0.435 for male and female first-graders, respectively, and 0.440 and 0.445 for male and female seventh-graders, respectively). We previously reported that this new exponential correction of the QT interval may be useful for eliminating the effect of heart rate in school-aged children. Computer analyses detected 13 children with abnormally prolonged eQTc. All of the children who had abnormal QTc values by conventional QTc criteria also had abnormal eQTc values using the new criteria. Nine of these 13 children were ultimately confirmed to have a prolonged QT interval. Six cases of QT prolongation were detected that would not have been found if conventional screening criteria were used, since these cases had heart rates greater than 75 beats/min. One child had parents who were deaf. This case would not have been detected if only conventional screening were used. These results suggest that exponential correction of the QT interval (eQTc) is useful for prospectively screening large populations for evidence of QT prolongation.

Confirmation that the conotruncal anomaly face syndrome is associated with a deletion within 22q11.2.

The so-called "conotruncal anomaly face syndrome" (CTAFS) is characterized by a peculiar facial appearance associated with congenital heart disease (CHD), especially cardiac outflow tract defects such as tetralogy of Fallot (TOF), double outlet right ventricle (DORV), and truncus arteriosus (TAC). CTAFS and the DiGeorge anomaly (DGA) have many similar phenotypic characteristics, suggesting that they share a common cause. In many cases DGA is known to be associated with monosomy for a region of chromosome 22q11.2. Fifty CTAFS patients and 10 DGA patients, 11 parents couples and 10 mothers of CTAFS patients, and 3 parents couples and 2 mothers of DGA patients were examined by fluorescent in situ hybridization (FISH) using the N25 (D22S75) DGCR probe (Oncor). Monosomy for a region of 22q11.2 was found in 42 CTAFS, 9 DGA, 4 mothers, and 1 father who had CTAF without CHD. The remaining 8 CTAFS patients 1 DGA patient and 1 mother who had questionable CTAF without CHD, showed no such chromosome abnormality. For the control, 60 patients who had CHD without CTAF or other known malformation syndromes were examined and had no deletion of 22q11.2. Therefore, we conclude that CTAFS is a part of the CATCH 22 syndrome; cardiac defects, abnormal faces, thymic hypoplasia, cleft palate, and hypocalcemia (CATCH) resulting from 22q11.2 deletions.

Antenatal diagnosis of tetralogy of Fallot with absent pulmonary valve accompanied by hydrops fetalis and polyhydramnios.

The case presented is an antenatal diagnosis of tetralogy of Fallot with absent pulmonary valve which was accompanied by hydrops fetalis and polyhydramnios with an absent stomach echo. Absent pulmonary valve was diagnosed by a cystic, pulsatile, aneurysmal dilatation of pulmonary arteries and a relatively small pulmonary valve annulus without a definite valve echo, in which a typical to-and-fro flow pattern was detected by the Doppler flow analysis. We will discuss some plausible roles of the grossly enlarged pulmonary arteries on hydrops fetalis and polyhydramnios.

Right aortic arch with aberrant retroesophageal innominate artery: a report of 2 cases and review of the literature.

We describe two patients of right aortic arch associated with aberrant retroesophageal innominate artery. One case was associated with tetralogy of Fallot and a tortuous left common carotid artery originating from the retroesophageal innominate artery. Tetralogy of Fallot associated with this kind of aortic arch anomaly has never before been reported. The other case was associated with a perimembranous ventricular septal defect. Symptoms such as dyspnea, dysphagia and recurrent respiratory infection due to the compression by the vascular anomaly were not noted in these two cases. The morphological findings are indicative of a double aortic arch with an interruption of the left arch proximal to the common carotid artery.

Abnormal development of fourth aortic arch derivatives in the pathogenesis of tetralogy of Fallot.

Aortic arch (AoA) anomalies were studied in 233 patients with tetralogy of Fallot (TOF) of whom some had coexisting pulmonary atresia (PA). There was a 23% incidence of a right AoA in patients without PA, 21% in those with both PA and persistent ductus arteriosus (PDA), and 50% in those with PA and major aortopulmonary collateral arteries (MAPCAs). There was a 5% incidence of an aberrant subclavian artery in patients without PA and a 16% incidence in those with PA and MAPCAs. In this cohort an elongated ascending aorta was observed both with and without high aortic arch. These aortic arch anomalies were frequently associated with PA and MAPCAs.

Hemodynamic characteristics in neural crest cell-excised chick embryo.

Damage to premigratory cranial neural crest cells results in cardiovascular anomalies of so-called conotruncal anomaly. In one report, it was suggested that hemodynamic alteration would precede abnormal cardiovascular morphogenesis. We repeated this hemodynamic study in neural crest cell-excised chick embryos and found that there was no difference in heart rate and blood pressure between the treated embryos (n = 11; 164 +/- 3 beats per min (BPM) and 0.75 +/- 0.03 mmHg, respectively) and control embryos (n = 7; 160 +/- 6 BPM and 0.72 +/- 0.07 mmHg, respectively). The response of heart rate to acetylcholine was less (P less than 0.05) in the treated embryos (-13% +/- 2%) than in the control (-20% +/- 2%). Thus, the present data do not support the hypothesis that alterations in blood pressure and heart rate are causally related to abnormal cardiovascular morphogenesis. The developmental significance of subtle functional changes in neural crest-extirpated embryos in response to cholinergic challenge is unclear.

Cardiovascular malformations induced by bromodeoxyuridine in the chick embryo.

For the study of morphogenesis and early embryonic development, 5-bromodeoxyuridine (BUdR), a halogenated analogue of thymidine, is incorporated into replicating DNA and serves as a valuable tool. To study the teratogenicity of BUdR on the developing chick cardiovascular system, we topically administered graded doses of BUdR (32.6-325.6 nmol) in ovo during Hamburger-Hamilton stages 15 to 16. We also administered to a parallel group of embryos corresponding nanomole doses of thymidine during identical stages of development. In the thymidine-treated group, survival rates and cardiovascular anomaly rates did not differ statistically from those in the chick Ringer's control group. Both survival rates and cardiovascular anomaly rates in the BudR-treated group were dose-responsive. Among 78 embryos with cardiovascular anomalies induced by BUdR, vascular malformations were found in 96%. These anomalies included interruption of the right fourth aortic arch, absence or hypoplasia of the right and/or left sixth aortic arch, and persistence of the left fourth aortic arch. Interruption of the right fourth aortic arch was always associated with intracardiac anomalies. Intracardiac anomalies were found in 54% of the embryos; these included ventricular septal defect, double outlet right ventricle, and persistent truncus arteriosus. Subclavian artery malformations were noted in 95% of the embryos. Possible mechanisms for BUdR-induced malformations in the cardiovascular system of the chick are discussed.

Pathogenesis of persistent truncus arteriosus and dextroposed aorta in the chick embryo after neural crest ablation.

To investigate the contribution of cranial neural crest cells to the developing cardiovascular system in the chick embryo, cauterization of various regions of cranial neural crest was performed. Five regions may be distinguished, each of which contributes mesenchyme to pharyngeal (branchial) arches 1 through 4 and 6. Ablation of arch 3, 4, and 6 regions resulted in a high incidence of persistent truncus arteriosus (PTA) associated with anomalies of the aortic arch. Dextroposed aorta (DPA) or anomalies of the inflow tract were found in all ablation groups. Although anomalies of the aortic arch arteries were induced in all ablation groups and were usually associated with intracardiac anomalies, those of the third and right fourth aortic arch were most frequent in the arch 4 and arch 4 + 6 groups. Anomalies of the sixth aortic arch were most frequent after extensive ablations that included the arch 6 region. We speculate that PTA is a direct result of the decreased population of mesenchymal cells derived from the arch 3 through 6 neural crest regions. DPA or anomalies of the inflow tract may be related to altered hemodynamics due to anomalies induced by neural crest ablation. Anomalies of the aortic arch arteries may be caused by either the direct or indirect process.

Total one-stage repair of interrupted aortic arch associated with aortic septal defect and patent ductus arteriosus.

Successful total repair in one stage was performed in a 3-year-old girl who had interrupted aortic arch associated with aortic septal defect and patent ductus arteriosus. Surface-induced deep hypothermia and interrupted perfusion were used. The results of postoperative catheterization and angiocardiographic studies are analyzed, and the literature and results of previous surgical attempts at correction are reviewed.