Synthesis of extracellular matrix and adhesion through beta(1) integrins are critical for fetal ventricular myocyte proliferation.

Extracellular matrix (ECM) regulates vascular smooth muscle cell proliferation. The role of ECM in myocardial growth is unexplored. We sought to determine whether human fetal ventricular myocytes (HFVMs) produce ECM and whether synthesis and attachment to ECM are necessary for their epidermal growth factor (EGF)-dependent and -independent proliferation. Cultured HFVMs proliferate in the presence but not absence of serum and EGF, as determined by increase in cell number and [(3)H]thymidine and [(14)C]leucine incorporation (measures of DNA and protein synthesis, respectively). Using a cyanogen bromide digestion technique to measure collagen and elastin and using affinity chromatography for fibronectin, we found that HFVMs synthesized collagen and fibronectin but not elastin. HFVMs grown on exogenous ECM (including fibronectin and type I collagen and laminin) demonstrated no change in proliferation or DNA and protein synthesis with or without EGF. However, inhibition of collagen synthesis using cis-4-hydroxyproline resulted in a decrease in EGF-related HFVM proliferation and DNA and protein synthesis, which was reversed by exposure to L-proline but not by growth on type I collagen. Use of beta(1) but not beta(3) integrin antibody to inhibit cell interaction with ECM resulted in a decrease in HFVM proliferation and DNA and protein synthesis in response to EGF. Furthermore, EGF-dependent proliferation was enhanced by alpha(1)beta(1) and alpha(5)beta(1) antibodies that act as functional ligands, but not alpha(3)beta(1), the only beta(1) subtype expressed in adult myocytes. In conclusion, proliferating HFVMs synthesize collagen and fibronectin. The proliferative response of HFVMs to EGF requires the synthesis of collagen as well as attachment to specific alpha/beta(1) integrin heterodimers.

Prenatal diagnosis of right ventricular outflow tract obstruction with intact ventricular septum, and detection of ventriculocoronary connections.

OBJECTIVES: To determine the accuracy of prenatal diagnosis of pulmonary atresia and intact ventricular septum (PAIVS), and pulmonary stenosis, including prenatal detection of ventriculocoronary connections, to evaluate heart size during the prenatal period, and to evaluate the outcome. DESIGN AND PATIENTS: Medical records of 20 cases with prenatally diagnosed PAIVS and pulmonary stenosis were reviewed retrospectively. Prenatal and postnatal echocardiography were also reviewed and dimensions of the ventricles and vessels were measured retrespectively. RESULTS: Of 20 prenatal diagnoses (15 PAIVS and five pulmonary stenosis), 16 were confirmed as correct. One critical pulmonary stenosis case had been diagnosed as PAIVS prenatally; three had no confirmation. Eight pregnancies were terminated, three had no active treatment, and nine were treated; all survived. Of 13 assessed with ventriculocoronary connections prenatally, seven were diagnosed correctly (four with, three without ventriculocoronary connections), but one was falsely positive; five had no confirmation. The more prominent hypoplasia of the main pulmonary artery and the tricuspid valve annulus, and the sigmoid shape of the ductus arteriosus, seemed to be associated with the presence of ventriculocoronary connections. CONCLUSIONS: Current prenatal echocardiography can accurately diagnose right ventricular outflow tract obstruction and ventriculocoronary connections. Prenatal detection of this constellation of abnormalities aids in family counselling and decisions on postnatal management.

[Scimitar syndrome: series of 12 cases]. / Síndrome de la cimitarra: serie de 12 casos.

Our experience in 12 cases of pediatric patients with scimitar syndrome is reported. Except for one, all of them presented cardiac or respiratory manifestations. The symptomatology was related to associated defects (3 atrial septal defects and 1 multiple peripheric pulmonary stenosis), degree of pulmonary hypoplasia, size of the right to left shunt and pulmonary hypertension. 3 patients underwent surgical treatment. One of them died during operation and the other two have had a good evolution. Nine patients with later respiratory manifestations have improved their condition progressively without surgical intervention. Therapeutic approach for patients with scimitar syndrome, respiratory manifestations and onset beyond the neonatal period, should be conservative.

Hearts with concordant ventriculoarterial connections but parallel arterial trunks.

OBJECTIVES: To determine the characteristic morphological features of hearts with concordant ventriculoarterial connections and parallel arterial trunks, and to provide unequivocally a method to describe their anatomy. DESIGN, METHODS AND PATIENTS: The entire cardiac database and cardiac pathological archive at the Hospital for Sick Children, Toronto, Ontario, Canada, was interrogated to identify all patients with concordant ventriculoarterial connections and parallel arterial trunks. The clinical records, autopsy reports and actual cardiac specimens of those who underwent autopsy, were reviewed. RESULTS: 8 cases meeting our criteria were identified. The infundibular anatomy was variable, including four hearts with bilateral infundibulums, three with subpulmonary infundibulums and one with bilaterally absent infundibulums. Considerable variability was also found in the type of atrial arrangement, along with the morphology of the atrioventricular junctions. The most common findings were the usual atrial arrangement (n = 5), left juxtaposition of the right atrial appendages (n = 3), an atrial septal defect (n = 6), univentricular atrioventricular connection (n = 5), ventricular septal defect (n = 8) and pulmonary obstruction (n = 4). In addition, five specimens had either a single coronary artery or two coronary arteries arising from the anticipated right coronary aortic sinus. CONCLUSIONS: Concordant ventriculoarterial connections with parallel arterial trunks can be found in a variety of segmental combinations. An accurate diagnosis of these rare hearts can be achieved by detailed analysis of not only the ventriculoarterial connections but also the infundibular anatomy and the spatial relationship of the arterial trunks. Particular attention to the coronary arteries is warranted.

Heart rate and cardiac output after atropine in anaesthetised infants and children.

PURPOSE: Heart rate is considered to be a major determinant of cardiac output in infants and small children but the relationships between age, heart rate and cardiac output in humans have never been clearly established. This study was designed to determine the change in cardiac output following atropine iv to anaesthetised infants and small children. METHODS: Following Institutional Ethics Committee approval and written-informed consent, 20 ASA I or II unpremedicated patients aged from 1 to 36 mo were studied. Anaesthesia was induced with 5 mg.kg-1 thiopentone, 2 micrograms.kg-1 fentanyl and maintained with halothane 0.5% in nitrous oxide 66% in oxygen. Vecuronium 0.1 mg.kg-1 was used to provide muscular relaxation. Cardiac output was measured by non-invasive transthoracic blind continuous-wave Doppler echocardiography before and after the administration of 0.02 mg.kg-1 atropine iv. RESULTS: Atropine increased both heart rate and cardiac index by 31.1 +/- 12.8% and 29.4 +/- 17.3% respectively (P < 0.05). The cardiac index before atropine was 5.1 +/- 1.2 L.min-1.m-2 and the increase after atropine varied widely from 1.4 to 52.1%. Although atropine did not alter the overall stroke index the recorded changes ranged from -20.8 to +18.0%. There was no association between age and either cardiac index or % change in cardiac index after atropine. However, there was a positive but weak correlation between percentage change in heart rate and cardiac output (r2 = 0.46). CONCLUSION: Atropine causes a variable increase in cardiac output in infants and children aged between 1 and 36 mo. The change in cardiac output, considering the limits of the transthoracic echocardiography methodology, suggests that this is related to the increase in heart rate but is not dependent of age.

Evolution of fetal ventricular aneurysms and diverticula of the heart: an echocardiographic study.

Due to the rarity of congenital ventricular diverticula and aneurysms, their natural history remains unclear. An excellent prognosis has been suggested for those cases diagnosed during fetal life: From October 1992 to January 1996 seven fetuses were diagnosed with ventricular diverticula or aneurysms. Gestational age ranged from 18 to 36 weeks. The indications for fetal echocardiogram were cardiomegaly, abnormal four-chamber view, a large pericardial effusion, and hydrothorax. Echocardiography revealed a moderate sized apical left ventricular aneurysm (2), a small subvalvular right ventricular diverticulum (1), small apical right ventricular diverticulum (2), a large submitral left ventricular aneurysm (1), and a large diverticulum arising from the lateral free wall of the left ventricle (1). Decreased left ventricular function was detected in three fetuses with left ventricular aneurysms. Two fetuses with large lesions, developed hydrops and died in utero. Postnatal echocardiograms confirmed prenatal findings in all survivors. All infants remained asymptomatic, with age on follow-up from 8 to 24 months. An accurate diagnosis of ventricular diverticula and aneurysms is feasible prenatally. Outcome depends on the size and progression of the lesion. The presence of a large pericardial effusion in three cases with a diverticula was noted.

Isolated ductal closure in utero diagnosed by fetal echocardiography.

In utero isolated ductal closure is uncommon and can lead to fetal hydrops and death if not recognized. Five fetuses were diagnosed prenatally by echocardiography. The reasons for referral were hydrops (2), cardiomegaly (1), polyhydramnios and choroid plexus cyst (1), and polyhydramnios and teratoma of the neck (1). Gestational age was median 32, range 18-41 weeks. Two mothers received indomethacin for polyhydramnios, with the echocardiogram performed 5 and 3 days after the last dose. Three had a negative history of drug ingestion. Fetal echocardiograms showed absent flow in the ductus arteriosus, dilated right ventricle with decreased function, and mild or moderate tricuspid and pulmonary insufficiency in all. The left ventricle was hypercontractile, with significantly increased left ventricular stroke output when compared to the right. Four fetuses were delivered by cesarean section and had an uneventful course. One fetus died shortly after birth due to airway obstruction from a large teratoma. Autopsy showed ductal constriction. Postnatal echocardiograms showed absent ductal flow and dilated right ventricle. On follow-up, survivors remained asymptomatic with cardiac size returning to normal. Premature closure of the ductus arteriosus should be considered in hydrops of unknown etiology, right ventricular dysfunction, and following indomethacin therapy. Urgent delivery results in an excellent prognosis.