bluuebunny/crossref_metadata_2025 huggingface dataset:
The prenatal diagnosis of, and short-term outcome for, patients with congenitally corrected transposition
Authors: Chiappa Enrico , Micheletti Angelo , Sciarrone Andrea , Botta Gianni , Abbruzzese Piero
Published: January 2005

Congenitally corrected transposition is a rare congenital anomaly, with only a few cases diagnosed and reported prenatally even in the largest fetal series. To determine the morphologic features and outcome for the lesion as recognized during fetal life, we reviewed the fetal and postnatal echocardiograms and medical records of 11 consecutive cases of congenitally corrected transposition. These were identified among 230 (4.7%) consecutive cases of structural cardiac disease referred to our fetal cardiology unit over a period of 4 years. The mean gestational age at diagnosis was 24.7 weeks. Reasons for referral were suspected complete transposition, abnormal position of the heart, and bradyarrhythmias. Associated cardiac lesions included an abnormal cardiac position in 6 cases, ventricular septal defect in 8, obstruction of the subpulmonary outflow tract in 6, tricuspid valvar displacement in 5, and complete atrioventricular block in 2. Only 3 of the cases had mild tricuspid regurgitation prior to birth. Termination was chosen in 4 cases with severe obstruction to pulmonary flow. Of the remaining cases, 2 patients died at 3 and 12 months after birth, respectively. Both developed significant tricuspid regurgitation associated with unexpected major arrhythmias. The remaining 5 patients are alive and relatively well at a mean follow-up of 25.4 months. An epicardial pacemaker was inserted in 1 because of complete atrioventricular block. We conclude that prenatal counseling must be guarded following the diagnosis of congenitally corrected transposition, even in fetuses with an apparently favorable state at initial examination. Some of these cases may undergo major and unexpected changes, particularly with regard to cardiac rhythm and tricuspid valvar function, with concomitant significant changes in prognosis.
Doppler echocardiographic predictors of outcome in newborns with persistent pulmonary hypertension
Authors: Fraisse Alain , Geva Tal , Gaudart Jean , Wessel David L.
Published: January 2005

Patients:We studied retrospectively the echocardiographic features of newborns with persistent pulmonary hypertension who had been randomised to receive inhaled nitric oxide or conventional therapy. We sought to identify the predictors of extracorporeal membrane oxygenation therapy, death, and response to inhaled nitric oxide.Results:Among 85 neonates studied, an extrapulmonary right-to-left shunt through either an oval foramen and/or an arterial duct was present in 80 (94%) cases. In the 64 patients (75%) with adequate images for measurements, left ventricular ejection fraction was normal or mildly depressed in 87%, but there was a decreased index of left ventricular output, inferior to 2 l/min/m2, in 61% of the cases. Using multivariate analysis, an exclusive right-to-left ductal shunt was found to be an independent predictor of death, with odds ratio of 7.8, and 95% confidence intervals from 1.2 to 52.8, with a p value of 0.04. There was also a non-significant trend toward greater use of extracorporeal membrane oxygenation in patients with a predominant left-to-right ductal shunt, the odds ratio being 0.13, with 95% confidence intervals from 0.01 to 1.22, and a p value of 0.07. In the 40 patients randomised to receive inhaled nitric oxide, 28 had a positive response as defined by a 20% reduction in the index of oxygenation as measured from the post-ductal arterial blood gas sample. A left-to-right atrial shunt increased the risk of failing to respond to inhaled nitric oxide, with an odds ratio of 7.46, 95% confidence intervals from 1.23 to 45.1, and a p value of 0.028.Conclusion:Detailed Doppler echocardiographic screening of patients with suspected persistent pulmonary hypertension of the newborn may refine the selection of groups for specific treatment, and identify risk factors.
Long-term outcomes after the atrial switch for surgical correction of transposition: a meta-analysis comparing the Mustard and Senning procedures
Authors: Khairy Paul , Landzberg Michael J. , Lambert Jean , O'Donnell Clare P.
Published: January 2005

Most adults with regular transposition (the combinations of concordant atrioventricular and discordant ventriculo-arterial connections) have undergone either the Mustard or Senning procedure in childhood. It is unclear whether adverse events differ according to the surgery performed. With this in mind, we conducted a systematic review and meta-analysis to compare long-term outcomes. We searched systematically entries to MEDLINE and EMBASE databases from January 1966 through August 2003, supplementing the search by secondary sources. Comparative studies were required to include at least 10 patients in each cohort of Mustard or Senning procedure, and to report overall survival. Data were extracted by two independent reviewers. We used a component approach to assess quality. On the basis of assessment of heterogeneity, we then used a random-effects model for pooled analyses. In all, we included seven studies, incorporating 885 patients. We found a trend towards lower mortality for the 369 patients undergoing a Mustard procedure when compared to 474 submitted to the Senning operation, with a hazard ratio of 0.63 and 95% confidence intervals between 0.35 and 1.14 (p = 0.13). This trend increased with the size of the sample (p = 0.004). Obstruction in the systemic venous pathway was more common in those having the Mustard procedure, with a risk ratio of 3.5 and 95% confidence intervals from 1.8 to 7.0 (p < 0.001), with a trend towards greater obstruction of the pulmonary venous pathway in those undergoing the Senning procedure, 7.6% vs. 3.8% (p = 0.27). A trend towards fewer residual shunts was observed for those with Mustard baffles, 7.0% vs. 14.1% (p = 0.10). Sinus nodal dysfunction, however, was more common after the Mustard procedure. Data regarding atrial tachydysrhythmias was inconclusive. Systemic cardiac failure and functional capacity, was similar. We conclude that outcomes are not uniform among patients submitted to the Mustard and Senning procedures. Knowledge of such differences may facilitate stratification of risk and follow-up.
Effect of peritoneal dialysis on intra-abdominal pressure and cardio-respiratory function in infants following cardiac surgery
Authors: Morris Kevin P. , Butt Warwick W. , Karl Tom R.
Published: January 2005

Objective:To investigate the relationship between dialysate volume, intra-abdominal pressure, and cardio-respiratory function in infants following cardiac surgery.Design:Prospective pilot study.Setting:Paediatric intensive care unit.Patients:Six infants undergoing peritoneal dialysis within 24 h of cardiopulmonary bypass.Interventions:Manipulation of the volume of dialysate at levels of 0, 10, 20, and 30 ml/kg in variable order.Measurements and main results:Intra-abdominal pressure was measured at each volume of dialysate via a pressure transducer connected to the dialysis catheter. Haemodynamic data was collected, including cardiac output, which was measured by thermodilution via a 3.5-French gauge catheter placed in the pulmonary arterial pathway. Respiratory data included PaO2, PaCO2, and dynamic compliance. Intra-abdominal pressure increased with increasing volume of dialysate (p < 0.001), though there was considerable variation between patients in the magnitude of increase. Intra-abdominal pressure remained low even with 30 ml/kg in the abdomen. In three infants, intra-abdominal pressure was re-measured in the absence of muscle relaxants, and was found to be higher in each case. No negative effects on cardiac output, markers of delivery of oxygen, or respiratory function were seen even at volumes of 30 ml/kg. Cardiac index was significantly higher with 10 ml/kg than when the abdomen was empty or contained a larger volume (p < 0.05).Conclusions:In this small group of infants, intra-abdominal pressure increased with increasing volumes of dialysate but remained low, even with 30 ml/kg in the abdomen, and was not associated with any deleterious effects on cardio-respiratory performance.
Outcomes after balloon dilation of congenital aortic stenosis in children and adolescents
Authors: Pedra Carlos A. C. , Sidhu Roger , McCrindle Brian W. , Nykanen David G. , Justo Robert N. , Freedom Robert M. , Benson Lee N.
Published: January 2005

Objectives:To determine the long-term outcomes and risk factors for, reintervention after balloon dilation of congenital aortic stenosis in children aged 6 months or older.Background:Although balloon dilation of congenital aortic stenosis has become a primary therapeutic strategy, few data are available regarding long-term outcomes.Methods:We carried out a retrospective review of 87 children who had undergone balloon dilation of the aortic valve at median age of 6.9 years.Results:The procedure was completed in 98% of the children, with an average reduction in the gradient across the valve of 64 ± 28%, and without mortality. Of the children, 76 had been followed for a mean of 6.3 ± 4.2 years. Reintervention on the aortic valve was required in 32 children, with 12 undergoing reintervention within 6 months, with 1 death. Another patient had died over the period of follow-up due to a non-cardiac event. Estimated freedom from reintervention was 86% at 1 year, 67% at 5 years, and 46% at 12 years. Parametric modeling of the hazard function showed a brief early phase of increased risk, superimposed on an ongoing constant risk. The only incremental risk factor for the early phase was a residual gradient immediately subsequent to the procedure greater than 30 mmHg. Incremental risk factors for the constant phase included the presence of symmetric valvar opening, and greater than moderate regurgitation immediately after dilation.Conclusion:Long-term survival was excellent, albeit that the need for further reintervention was high due to the palliative nature of the procedure.
Closure of a patent arterial duct in a septuagenarian with atrial fibrillation
Authors: Brockmeier Konrad , Hallscheidt Peter , Haller Christlieb
Published: January 2005

We occluded a large arterial duct in a patient with atrial fibrillation, using an Amplatzer duct occluder, with no residual shunt at the end of the procedure. Follow-up revealed recanalization, which was successfully treated with a 4 mm Amplatzer ASD occluder. It is speculated the reopening of the initially occluded duct was the consequence of anticoagulation needed because of the atrial fibrillation.
Pulmonary atresia with intact ventricular septum and antenatal left ventricular failure
Authors: Khoshhal Saad , Sandor George G. S. , Duncan Walter J.
Published: January 2005

Pulmonary atresia with intact ventricular septum has been described extensively, and it is recognized that associated abnormalities of the coronary arteries may cause ischemia. We describe a fetus, diagnosed antenatally as having pulmonary atresia with intact ventricular septum and severe hypoplasia of the right ventricle, who developed severe left ventricular dysfunction. We hypothesize that this is due to reduced coronary blood flow because of falling right ventricular volume in the presence of complete right ventricular coronary arterial dependence.
Intrapericardial giant left atrial appendage
Authors: Thomas Eapen , Salmon Anthony P. , Vettukattil Joseph J.
Published: January 2005

Contrary to what the name implies, the left atrial appendage is increasingly becoming an organ of clinical importance. Its role in the pathogenesis of thromboembolism is now well established. Enlargement of the appendage due to haemodynamic disturbances or anatomic weakness increases this risk, along with the potential for arrhythmia. We report a rare case of gross enlargement of the left atrial appendage within the pericardial cavity.
Review of an institutional experience of coronary arterial fistulas in childhood set in context of review of the literature
Authors: Holzer Ralf , Johnson Robert , Ciotti Giovanna , Pozzi Marco , Kitchiner Denise
Published: January 2005

Coronary artery fistulas are uncommon in children. We conducted a retrospective review of the case notes of 17 children who presented to our institution with the diagnosis of a coronary fistula since 1970. Their median age was 2.3 years. In five patients, there were associated congenital cardiac anomalies, with four having these as part of the spectrum of tetralogy of Fallot. Surgical correction was performed in nine patients, while in five closure was achieved using percutaneous embolization with coils. No complications or deaths were encountered related to the treatments chosen. In two patients, further procedures were needed to close residual fistulas. The median follow-up was 16 years, and on echocardiography, all fistulas appeared to be successfully closed, albeit that we lost three patients to follow up. We also conducted a review of 426 cases of coronary fistulas reported in children in the English literature. We have compared these findings with our institutional experience.
The variable clinical presentation of, and outcome for, noncompaction of the ventricular myocardium in infants and children, an under-diagnosed cardiomyopathy
Authors: Ali Sulafa K. M. , Godman Michael J.
Published: January 2005

Noncompaction of the ventricular myocardium is increasingly recognized as an important cause of cardiomyopathy. Its echocardiographic definition, however, is not yet clearly refined, and differentiation from other conditions with hypertrabeculation can be difficult. We report a prospective short-term follow-up of 15 children with noncompaction, excluding those with associated complex congenital cardiac disease.

The clinical presentation and outcome were variable, with 2 patients being asymptomatic. For 5 patients, presentation was with cardiac failure due to depressed myocardial function. The function deteriorated in two, remained the same in two, and improved in the other patient. Cardiac failure due to mitral regurgitation was the mode of presentation in 2 patients with preserved myocardial function, one of whom needed replacement of the mitral valve. In 6 patients (40%), symptoms of cardiac failure were due to noncomplex congenital cardiac disease. All of them had ventricular septal defects. In addition, two had cleft mitral valves, and one had a large persistently patent arterial duct. The diagnosis of noncompaction was initially missed on more than one echocardiographic study in one-third of our patients. We conclude that noncompaction is under-diagnosed, and is not as rare as is thought. In children, it is often associated with other cardiac lesions that can cause cardiac failure in the presence of preserved myocardial function.
The biological “scrabble” of pulmonary arteriovenous malformations: considerations in the setting of cavopulmonary surgery
Authors: Freedom Robert M. , Yoo Shi-Joon , Perrin Donald
Published: January 2005

Pulmonary arteriovenous fistulas are vascular malformations, which, by virtue of producing abnormal vascular connections proximal to the units of gas exchange, result in intrapulmonary right-to-left shunting. These malformations or fistulas reflect at least in part disordered angiogenesis, and less commonly recruitment and dilation of pre-existing vascular channels.1Pulmonary arteriovenous fistulas occur in a number of diverse clinical settings. Such fistulas are a well-established feature of the Weber–Osler–Rendu complex, or hereditary haemorrhagic telangiectasia, an autosomal dominant vascular dysplasia characterized by mucocutaneous telangiectasis, epistaxis, gastrointestinal haemorrhage, and arteriovenous malformations in the lung, brain, liver and elsewhere.2,3They are also seen in the patient with acute or chronic liver disease, disease that is usually but not invariably severe, or those with non-cirrhotic portal hypertension. They may occur as congenital malformations, single or diffuse, large or small in isolation, and when large or extensive enough may result in hypoxaemia, clinical cyanosis, and heart failure.3Cerebral vascular accidents are also a well-known complication of this disorder.3An extensive literature has accumulated with regard to the pulmonary arteriovenous fistulas seen in the setting of the Weber–Osler–Rendu complex, and there is considerable information on the genetics, basic biology, clinical findings, complications and therapeutic interventions of these malformations in the setting of this syndrome.4These issues, however, are not the primary considerations of this review, although some aspects of this fascinating disorder will be discussed later. Rather the focus will be on pulmonary arteriovenous malformations that develop in the setting of cavopulmonary surgery, and their relationship to the pulmonary arteriovenous fistulas occurring in the hepatopulmonary syndrome. The complex tapestry of these overlapping and intersecting clinical observations will be unfolded in the light of their chronology.
Solitary trunk from the right ventricle with a cleft mitral valve simulating the trifoliate left valve of an atrioventricular septal defect with common atrioventricular junction
Authors: Sharratt Geoffrey P. , Anderson Robert H.
Published: January 2005

We report a case of a true cleft in the anterior leaflet of the mitral valve. The cleft, however, is directed toward the ventricular septum, and the left ventricular papillary muscles have the same arrangement as seen in the setting of a common atrioventricular orifice. The atrioventricular septum is intact. This appearance reflects the presence, in this patient, of right ventricular origin of a solitary arterial trunk, so that there was no outflow tract within the left ventricle to interpose between the mitral valve and the septum.
Left cervical aortic arch with proximal obstruction
Authors: Öztunç Funda , Babaoĝlu Kadir , Türkoĝlu Halil
Published: January 2005

Cervical aortic arch is a rare congenital anomaly. We present a case of left-sided cervical aortic arch, found in a patient with mitral regurgitation, mitral stenosis, and a regurgitant bicuspid aortic valve. There was atypical obstruction proximally within the arch. The obstructive segment was resected, and corrected by performing an end-to-side anostomosis. Mitral valvoplasty was performed in the same surgical procedure. To the best of our knowledge, a cervical arch has not previously been described with such atypical obstruction, and in association with multiple lesions involving the left heart.
The distance from the Amplatzer septal occluder to the mitral valve in patients undergoing interventional closure of defects in the oval fossa increases with growth of the patient
Authors: English Robert F. , Ettedgui Jose A.
Published: January 2005

The Amplatzer septal occluder is an alternative to operative closure of atrial septal defects within the oval fossa. An issue when deploying the device is its distance from the mitral valve. The purpose of this study is to determine how this distance changes with growth of the patient. We identified, through a review of charts, all patients undergoing closure of defects within the oval fossa by insertion of an Amplatzer septal occluder. Data were obtained from the echocardiogram 24 hours after closure, and at most recent follow-up, including left ventricular end-diastolic diameter, left atrial diameter, degree of mitral valvar regurgitation, body surface area, and distance from the device to the mitral valve. We divided the patients into 2 groups based upon change in body surface area. The first group had an increase in body surface area of at least 10%. All others were in the second group.

We inserted 55 Amplatzer septal occluders in 54 patients. Of these we excluded 17 patients, 1 because quality of images was inadequate, 1 who underwent placement of 2 devices, 1 in whom the device embolised to the left ventricle the day after deployment, and 14 who have not yet had a follow-up echocardiogram.

The group which exhibited an increase in body surface area of greater than 10% demonstrated an increase in distance from the device to the mitral valve, left ventricular end-diastolic, and left atrial diameters. Those who did not undergo significant growth had no increase in distance from the device to the mitral valve, but did have an increase in left atrial and left ventricular end-diastolic diameters. No patient developed mitral regurgitation. We conclude that, when deploying an Amplatzer septal occluder close to the mitral valve in children, the distance from the device to the mitral valve can be expected to increase with growth of the patient.
Molecular characterisation of neonatal cardiac hypertrophy and its regression
Authors: Gopinath Bamini , Trent Ronald J. , Yu Bing
Published: January 2005

Neonatal cardiac hypertrophy associated with diabetic pregnancy is transient and regresses naturally, but is associated with increased morbidity and mortality.

This study was undertaken to analyse the changes in expression of 5 cardiac genes, including atrial natriuretic peptide, α- and β-myosin heavy chain, and cardiac and skeletal α-actin genes, using a rat neonatal model, in which cardiac hypertrophy was induced via maternal diabetes.

In the hypertrophied left ventricle of neonates from diabetic mothers, the levels of mRNA from all the above genes except skeletal α-actin were increased by between 1.8- and 12-fold compared with the controls at birth (p < 0.05). In the first 28 days, the level of mRNA for α-myosin heavy chain increased slightly, while that for atrial natriuretic peptide and β-myosin heavy chain decreased continuously similar to the controls, but at a significantly faster rate. No significant difference between the two groups of neonates was observed in all 5 genes after 1 month, indicating complete regression.

Expression of 5 cardiac genes in the neonatal cardiac hypertrophy was characterised in both hypertrophic and regressive phases. Hypertrophic regression provides a unique model for the testing of new drugs or genetic modifying factors in cardiac hypertrophy.
Diagnosis, management, and results of treatment for aortopulmonary window
Authors: Mert Murat , Paker Tufan , Akcevin Atif , Cetin Gurkan , Ozkara Ahmet , Saltik Levent , Bakir Ihsan , Yildiz Cenk Eray
Published: January 2005

The aortopulmonary window is a communication between the ascending aorta and the pulmonary trunk in the presence of two separate arterial valves. This uncommon congenital anomaly is reported rarely in the literature. We present here our experience with 16 patients, emphasizing the importance of early closure of the defect by a transaortic approach.

We performed surgery on 16 patients over a period of 13 years using a transaortic approach under cardiopulmonary bypass. The median age of the patients at the time of operation was 6.5 months, with a range from 1 month to 11 years. Preoperative pulmonary arterial systolic pressure ranged from 30 to 100 mmHg. Associated cardiac anomalies were present in 7 of the patients, and were repaired at the same stage. The defect was between the ascending aorta and the proximal pulmonary trunk in 13 patients, and between the ascending aorta and the distal pulmonary trunk, with overriding of the orifice of the right pulmonary artery, in 3 patients. For closure, we used a patch of 0.4 mm Gore-Tex in 11, and gluteraldehyde-treated autologous pericardium in 5 of the patients.

One patient died during surgery. The mean follow-up period for the surviving 15 patients was 52.2 months, with a range from 12 to 130 months. All the patients were in good condition during the follow-up, and no residual defects have been detected.

Aortopulmonary window is a rare congenital cardiac anomaly, which can be repaired with very good operative results if surgery is performed before the development of irreversible pulmonary hypertension. We advise early correction of the defect with a transaortic patch, repairing all associated cardiac anomalies at the time of diagnosis.
Thirty years of experience with epicardial pacing in children
Authors: Noiseux Nicolas , Khairy Paul , Fournier Anne , Vobecky Suzanne J.
Published: January 2005

Due to underlying cardiovascular anatomy and size, epicardial pacing may be the preferred method of pacing in small children. To assess long-term safety, we reviewed all epicardial pacemakers implanted in children between 1971 and 2001. We found that 122 patients, with a median age of 5.4 years, had a total of 181 pacemakers and 260 electrodes implanted over a total follow-up of 789 patient-years. Of the total, 12 patients died after the first implantation, with one death attributable to dysfunction of the pacemaker. Reintervention was required in 75 patients after 5.0 ± 3.2 years, due to depletion of the battery in 45 patients (60%), fracture or dysfunction of electrodes in 27 patients (36%), and infection in 3 patients (4%). In univariate analyses, risk factors for reintervention were an approach via a median sternotomy, with a relative risk of 2.3 (p = 0.0087), and an indication for pacing other than atrioventricular block, with a relative risk of 1.7 (p = 0.0314). In multivariate analyses, the approach via the median sternotomy independently predicted the need for reintervention, with a relative risk of 2.1, and 95% confidence intervals from 1.1 to 4.1 (p = 0.0256). The longevity of the second pacemaker and/or its electrode, assessed in 26 patients, was 3.7 ± 2.6 years, not shorter than the first implantation (p = 0.4037). We conclude that epicardial pacing is a reliable means of achieving permanent pacing in children, with low morbidity and mortality. A substantial proportion, nonetheless, requires reintervention within five years, warranting meticulous follow-up.
Problems with the right ventricular outflow tract: a review of morphologic features and current therapeutic options
Authors: Vricella Luca A. , Kanani Mazyar , Cook Andrew C. , Cameron Duke E. , Tsang Victor T.
Published: January 2005

Repair of complex malformations that necessitate restoration of continuity between the right ventricle and the pulmonary arteries can now safely be performed with low morbidity and mortality. Major concerns still remain on the long-term outlook for these patients, and about the durability of the different prostheses used to restore that continuity, whether during initial correction or at the time of reintervention for failure of the conduit or pulmonary regurgitation. In this review, we discuss the salient morphologic features of the right ventricular outflow tract, and then focus on the indications for early and late intervention, current therapeutic options, and outcomes.
Divided left atrium with obstruction of pulmonary venous return in the setting of hypoplasia of the left heart
Authors: Monaco Sara E. , Gersony Welton M. , Thaker Harshwardhan M.
Published: January 2005

We describe an infant with hypoplasia of the left heart diagnosed prenatally who, at birth, had signs of severe pulmonary venous obstruction. Echocardiography indicated normally connecting pulmonary veins, and showed a paradoxical right-to-left shunt across a patent oval foramen. Postmortem examination revealed that the obstruction was due to a divided left atrium, or cor triatriatum sinister, with an imperforate muscular diaphragm separating completely the two components of the divided atrium.
Ventricular preexcitation associated with dilated cardiomyopathy: a causal relationship?
Authors: Emmel Mathias , Balaji Seshadri , Sreeram Narayanswami
Published: January 2005

Over a six year period, we identified four children with dilated cardiomyopathy associated with ventricular preexcitation, three in the absence of any documented tachyarrhythmias, and one with but a solitary episode of tachyarrhythmia. None of them had another identifiable aetiology for the cardiomyopathy. Based on the 12 lead electrocardiogram, and/or invasive electrophysiologic studies, we localised the accessory pathways to the right atrioventricular groove in all patients. We commenced antifailure medications in two of the four patients, but did not produce any measurable improvement in ventricular function. Catheter ablation was performed in two patients, with resolution of the cardiomyopathy. The ventricular preexcitation disappeared spontaneously in one child during follow-up, again with resolution of cardiomyopathy. The youngest patient continues to receive antifailure medications, albeit without improvement. We suggest, therefore, that dilated cardiomyopathy of reversible nature is associated with manifest ventricular preexcitation, even in the absence of sustained arrhythmias.
Implanting telehealth network for paediatric cardiology: learning from the Quebec experience
Authors: Bellavance Marc , Béland Marie J. , van Doesburg Nicolaas H. , Paquet Marc , Ducharme Francine M. , Cloutier Alain
Published: January 2005

The implementation committee of the Quebec Child Telehealth Network was formed in 1997, with a mandate to build a network dedicated to the diagnosis of congenital cardiac disease via telemedicine. We devised criterions for selection to determine which peripheral centres would be linked by telemedicine to the university-based services for paediatric cardiology provided in the Canadian Province of Quebec. The criterions included: distance from a university centre, number of births per year, and presence of an already-established outreach clinic for paediatric cardiology. The Quebec Network became operational in 2000, and was composed of 32 peripheral centres and 4 university centres. A total of 363 transmissions of echocardiograms occurred over a 3-year period from January 2000 to December 2002. Peripheral centres located at a distance greater than 100 kilometres from a university centre were 8.5 times more likely to use the network. Criterions other than distance did not influence whether or not a peripheral centre used the network. Cardiac abnormalities were identified in almost two-thirds of the transmissions. The use of the Quebec Network resulted in the avoidance of transfers or clinic visits to university hospitals in seven-tenths of cases. We conclude that distance greater than 100 kilometres from a centre offering subspecialty services in paediatric cardiology is the most important criterion for choosing the peripheral centres that are most likely to use a telehealth network. In its first three years of operation, the telehealth network had a major impact on the delivery of paediatric cardiac care, improving access to subspecialty services across the province.
Quality of life in children with pulmonary atresia and intact ventricular septum
Authors: Ekman-Joelsson Britt-Marie , Berntsson Leeni , Sunnegårdh Jan
Published: January 2005

Objective: To measure quality of life in children with pulmonary atresia and intact ventricular septum, and make comparisons with a healthy group of children from the general Swedish population. An additional aim was to compare quality of life in two subgroups, children undergoing biventricular and univentricular repair, the latter by establishment of the Fontan circulation. Methods: Quality of life was measured using a mailed questionnaire, taking into consideration the three spheres of personal, interpersonal, and external living conditions. In all, 52 children received the questionnaire, and the answers were compared with those of a random sample of 1856 healthy Swedish children. Results: We received responses from 42 children and parents. The overall differences between groups were small, and no difference was found when comparing the children undergoing univentricular as opposed to biventricular surgical repair. In terms of personal quality of life, we found a higher level of psychosomatic complaints, and lower satisfaction with their own and parent–child activities, in those with the congenital anomaly than in their normal peers. In terms of the interpersonal sphere, more time was available for those with malformed hearts, but the experience of support from the relatives was significantly lower. Conclusions: Overall, quality of life was equal between children with pulmonary atresia and intact ventricular septum and the children in the reference group. The personal psychological conditions were less favourable for children with pulmonary atresia and intact ventricular septum. The perceived lack of support from relatives was also higher in these families. No difference was found when comparing the children undergoing univentricular and biventricular surgical repair.
Long on QT and low on calcium
Authors: Bradley Timothy J. , Metzger Daniel L. , Sanatani Shubhayan
Published: January 2005

Acquired lengthening of the QT interval due to hypocalcaemia is a rare cause of arrhythmia in childhood. Early recognition, rapid institution of appropriate cardiac monitoring, and replacement therapy are essential. An endocrinal work-up may be necessary to exclude primary disorders of calcium metabolism. We report four cases documenting the varied clinical spectrum in which hypocalcaemic-induced prolongation of the QT interval and arrhythmia can occur in childhood.
Time‐course of deactivation of rat stomach ECL cells following cholecystokininB/gastrin receptor blockade
Authors: Ding X.‐Q. , Lindström E. , Håkanson R.
Published: January 2005

The so‐called enterochromaffin‐like (ECL) cells constitute 65–75% of the endocrine cells in the acid‐producing part of the rat stomach. They produce and secrete histamine and pancreastatin, a chromogranin A (CGA)‐derived peptide, in response to gastrin. Cholecystokinin (CCK)B/gastrin receptor blockade is known to suppress their activity.

We have examined the time course of the deactivation of the ECL cells following treatment with the selective CCKB receptor antagonists RP73870 and YM022. The drugs were given by continuous subcutaneous infusion for a time span of 1 h to 3 weeks and the serum gastrin concentration and various ECL cell parameters were measured (oxyntic mucosal histidine decarboxylase (HDC) activity, histamine and pancreastatin concentrations, HDC mRNA and CGA mRNA levels, and circulating pancreastatin concentration).

The two antagonists caused a prompt and dramatic decline in the oxyntic mucosal HDC activity and HDC mRNA level. The HDC activity started to decline after 1–2 h, was reduced by 60–70% after 6 h and was maximally suppressed (80–90%) after 24–48 h. The HDC mRNA level was reduced after 12 h and was at about 20% of the pretreatment level after 2–4 days of infusion. The ECL cell histamine concentration was lowered by about 50% after 7–10 days.

RP73870 and YM022 lowered the serum pancreastatin concentration and the oxyntic mucosal CGA mRNA level. The serum pancreastatin concentration was reduced by 40% after 6 h and the reduction was maximal after 2–3 days. A decline in the oxyntic mucosal CGA mRNA level was noted after 12 h with a maximal reduction after 2–4 days of infusion. The ECL cell pancreastatin concentration was reduced by 30–40% after 3 weeks.

The infusion of RP73870 and YM022 induced hypergastrinaemia. The serum gastrin concentration started to rise after 2–4 h, there was a 2 fold increase after 6 h and maximal increase (3–4 fold) after 2–3 days of treatment.

In conclusion, CCKB/gastrin receptor blockade promptly deactivates the ECL cells. Deactivation, manifested in a greatly reduced HDC activity, was apparent after 1–2 h of the infusion. The serum pancreastatin concentration and the oxyntic mucosal HDC mRNA and CGA mRNA levels were greatly reduced after 1–2 days. The ECL cell concentrations of histamine and pancreastatin declined quite slowly by comparison.

British Journal of Pharmacology (1997) 122, 1–6; doi:10.1038/sj.bjp.0701316
Prominent role of intracellular Ca2+ release in hypoxic vasoconstriction of canine pulmonary artery
Authors: Jabr Rita I. , Toland Helen , Gelband Craig H. , Xia Wang Xiao , Hume Joseph R.
Published: January 2005

The possible role of sarcoplasmic reticulum (SR) Ca2+ stores in hypoxic pulmonary vasoconstriction (HPV) is not well understood. In order to assess the possible role of intracellular Ca2+ release from SR Ca2+ stores in HPV, we examined the effects of: (1) ryanodine (10 μM) depletion of intracellular Ca2+ stores, and (2) thapsigargin (THAPS, 2 μM) or cyclopiazonic acid (CPA, 10 μM) depletion of intracellular Ca2+ stores on HPV in canine pulmonary artery.

Isometric tension was measured from arterial ring suspended in Krebs‐Henseliet solution (K‐H) bubbled with 95%O2/5%CO2. Hypoxia was induced by bubbling phenylephrine (PE, 1 μM) precontracted rings with 95%N2/5%CO2. HPV was observed in both intact and endothelial‐denuded arteries and expressed as % of maximal KCl contraction (%Tkmax)=21.3±3.2%; n=13 and 21.7±4%; n=4, respectively.

When SR caffeine sensitive Ca2+ stores were depleted by pretreatment with ryanodine and brief caffeine (15 mM) exposure, the hypoxic response was signifcantly reduced to 19.1±9.2% of the control hypoxic contraction (n=7; P<0.001) with little or no effect on PE or KCl contractions. On the other hand, in normoxic rings pretreated with THAPS or CPA, the PE responses were significantly reduced (%Tkmax=18.2±3.1% compared to 39.0±3.9% in control; n=16; P<0.001; %Tkmax=3.4±1.6% compared to 49.9±7.9% in control; n=6; P<0.001; respectively) with no significant effect on caffeine‐induced contractions, suggesting that both THAPS and CPA preferentially deplete InsP3‐sensitive Ca2+ stores, without affecting the caffeine‐sensitive Ca2+ store; consistent with the existence of separate and independent InsP3 and caffeine‐sensitive Ca2+ stores in this preparation.

When hypoxia was induced in the presence of THAPS or CPA, developed tension was significantly larger than control (%Tkmax=64.5±6.0%; n=16; P<0.05%; %Tkmax=78.2±15%; n=6; P<0.05; respectively), was partially blocked by nisoldipine (10 μM) and ryanodine (%Tkmax=20.3±3.7%; n=6), and nearly completely blocked by SK&F 96365 (50 μM). However, the actions of SK&F 96365 appeared to be nonselective since this compound also significantly reduced contractions elicited by KCl, PE and caffeine.

Finally, evidence was obtained suggesting: (a) that at least some of the Ca2+ released from the caffeine‐ and ryanodine‐sensitive Ca2+ stores by hypoxia may be taken up and buffered by the InsP3‐sensitive Ca2+ stores, and (b) the apparent dependence of HPV on extracellular Ca2+ entry pathways may be partially due to the dependence of the Ca2+ content of intracellular SR Ca2+ stores on sarcolemmal Ca2+ entry pathways.

These data suggest that caffeine‐ and ryanodine‐sensitive SR Ca2+ stores contribute significantly to HPV under normal conditions and, in the presence of THAPS or CPA, an additional nisoldipine‐ and ryanodine‐insensitive Ca2+ entry pathway is evoked by hypoxia.

British Journal of Pharmacology (1997) 122, 21–30; doi:10.1038/sj.bjp.0701326
Action of ryanodine on neurogenic responses in rat isolated mesenteric small arteries
Authors: Garcha Robinder S. , Hughes Alun D.
Published: January 2005

Rat mesenteric arteries (∼250 μm) were set up in a single‐channel isometric myograph designed to allow fluorescence measurements concurrent with field stimulation of intramural nerves. Vessels were loaded with 6 μM fura‐2AM for 2 h and simultaneous recordings of neurogenic contraction (force) and intracellular calcium [Ca2+]i were obtained. In other experiments, arteries were loaded with 1 μCi ml−1 [3H]‐noradrenaline (NA) for 30 min in order to measure release of [3H]‐NA in response to field stimulation to examine whether ryanodine directly inhibited neuronal release of NA.

Arteries were activated by single intermittent field stimulation or continuously to excite intrinsic sympathetic nerves, or by cumulative addition of noradrenaline (1 nM–10 μM) to the bathing solution.

Pre‐incubation with ryanodine markedly inhibited the contraction and [Ca2+]i release in response to single‐pulse nerve stimulation. Ryanodine also inhibited an early phasic component of the response to continuous field stimulation and reduced the rate of rise in force in response to continuous field stimulation. However, stable maximal contraction and [Ca2+]i in response to continuous field stimulation as well as maximal responses to exogenous NA were unaffected. Release of [3H]‐NA in response to single intermittent field stimulation was not affected by ryanodine when compared to vehicle.

Our results suggest that brief intermittent activation of intramural sympathetic nerves increases [Ca2+]i and contracts small arteries primarily by releasing Ca2+ from a ryanodine‐sensitive intracellular store. In contrast, the stable rise in tone and [Ca2+]i resulting from continuous nerve stimulation may largely depend on sources of Ca2+ other than the ryanodine‐sensitive intracellular store.

British Journal of Pharmacology (1997) 122, 142–148; doi:10.1038/sj.bjp.0701337
Inhibition by ATP of calcium oscillations in rat cultured hippocampal neurones
Authors: Koizumi Schuichi , Inoue Kazuhide
Published: January 2005

The effect of adenosine 5′‐triphosphate (ATP) on glutamatergic synaptic transmission in hippocampus was examined by an indicator of intracellular Ca2+ oscillations. These oscillations were postsynaptic responses by glutamate released from presynaptic sites. ATP completely inhibited the oscillations in a concentration‐dependent manner.

The ATP‐induced inhibition was mediated via P2‐purinoceptors since ATP exhibited the inhibitory action even in the presence of P1‐purinoceptor antagonists. Also non‐hydrolysable ATP analogues and uridine 5′‐triphosphate (UTP) inhibited the oscillation.

The rank order of agonist potency of ATP analogues for inhibition of the Ca2+ oscillation was as follows: 2‐methyl‐thio‐adenosine 5′‐triphosphateATP>adenosine 5′‐O‐(3‐thiotriphosphate)>UTP>α,β‐methylene‐adenosine 5′‐triphosphate. These inhibitory effects were insensitive to suramin. Judging from this rank order of potency, the inhibitory P2‐purinoceptor could be assigned to a subclass of GTP‐binding protein coupled‐type receptors.

The site of action of ATP was thought to be presynaptic since ATP did not affect the postsynaptic Ca2+ responses by glutamate. These results suggest the existence of a presynaptic inhibitory P2‐receptor that inhibits glutamate release in the hippocampus.

British Journal of Pharmacology (1997) 122, 51–58; doi:10.1038/sj.bjp.0701344
Selective inhibition of adenylyl cyclase by octopamine via a human cloned α2A‐adrenoceptor
Authors: Airriess Chris N. , Rudling Jane E. , Midgley John M. , Evans Peter D.
Published: January 2005

In this study we have compared the abilities of the enantiomers of the structural isomers of the phenolamines, octopamine and synephrine, and the catecholamines, noradrenaline and adrenaline, to couple selectively a human cloned α2A‐adrenoceptor, stably expressed in a Chinese hamster ovary (CHO) cell line, to G‐protein linked second messenger pathways mediating an increase and a decrease in cyclic AMP production.

The catecholamines couple the α2A‐adrenoceptor to both an increase and a decrease in the rate of cyclic AMP production. In the absence of pertussis toxin pretreatment both catecholamines tested showed a dose‐dependent decrease with a maximum at 100 nM. After pertussis toxin pretreatment they both produced a dose‐dependent increase in cyclic AMP production with a maximum at 10 μM.

The phenolamines, octopamine and synephrine were only able to couple the α2A‐adrenoceptor to a dose‐dependent decrease in cyclic AMP production at concentrations up to 1 mM, with the synephrine isomers being more potent than the corresponding octopamine isomers. The meta‐isomers of both phenolamines were more potent than the corresponding para‐isomers and the (−)‐enantiomers were more potent than the (+)‐enantiomers. Thus, (−)‐meta‐synephrine [(−)‐phenylephrine] was the most effective isomer tested with an observable decrease occurring between 100 nM and 1 μM.

The effects of octopamine and the catecholamines on the decrease in cyclic AMP production were additive at submaximal concentrations, whilst octopamine reduced the stimulant effect of submaximal concentrations of noradrenaline on cyclic AMP production after pertussis toxin pretreatment.

The time courses of the inhibitory effects of both meta‐octopamine and noradrenaline were parallel and peaked after a 1 min exposure to the agonist. In contrast, the stimulant effects of noradrenaline after pertussis toxin pretreatment were of a much slower time course with a maximum effect occurring after a 5 min incubation period.

Since octopamine and synephrine occur naturally in, and are co‐released with catecholamines from, mammalian tissues, the results of the present study suggest that the human cloned α2A‐adrenoceptor can be coupled selectively by different endogenous agonists to G‐protein pathways mediating the regulation of adenylyl cyclase activity.

British Journal of Pharmacology (1997) 122, 191–198; doi:10.1038/sj.bjp.0701348
Anti‐thrombotic effects and bleeding risk of AJvW‐2, a monoclonal antibody against human von Willebrand factor
Authors: Kageyama Shunsuke , Yamamoto Hiroshi , Nagano Mitsuyo , Arisaka Harumi , Kayahara Takashi , Yoshimoto Ryota
Published: January 2005

A murine anti‐human vWF monoclonal antibody, AJvW‐2, was developed that inhibited the interaction between platelet glycoprotein Ib (GPIb) and von Willebrand factor (vWF) during the ristocetin‐ (IC50=0.7±0.1 μg ml−1) and botrocetin‐ (IC50=1.8±0.3 μg ml−1) induced aggregation of human platelets.

AJvW‐2 inhibited the high shear stress (10.8 N m−2) induced aggregation of human platelets dose‐dependently with an IC50=2.4±0.3 μg ml−1, but had no effect on low shear stress induced platelet aggregation (1.2 N m−2) up to 100 μg ml−1.

AJvW‐2 also inhibited the high shear stress (5.0 N m−2) induced adhesion of human platelets to collagen I with the same efficacy (IC50=2.4±0.3 μg ml−1), but had no effect at low shear conditions (1.5 N m−2).

AJvW‐2 inhibited the botrocetin‐induced aggregation of platelets from guinea‐pig, rat, rabbit, dog and pig at the same concentration range as human platelets; it likewise also inhibited the high shear stress induced aggregation and adhesion to collagen I of guinea‐pig platelets.

AJvW‐2 prevented arterial thrombus formation in guinea‐pigs at a dose of 100 μg kg−1 without prolonging the template bleeding time, whereas the GPIIb/IIIa antagonist lamifiban mediated inhibition of thrombosis at 1000 μg kg−1 was accompanied by a significant prolongation of the bleeding time.

These results suggest that AJvW‐2 is a potent inhibitor of the GPIb‐vWF interaction and a potential novel antithrombotic agent with lower bleeding risk than GPIIb/IIIa antagonists.

British Journal of Pharmacology (1997) 122, 165–171; doi:10.1038/sj.bjp.0701354