In vivo persistence of expanded clones specific for bacterial antigens within the human T cell receptor alpha/beta CD4-8- subset.

We analyzed the T cell receptor (TCR) rearrangements of 100 TCR-alpha/beta CD4-CD8- (double negative [DN]) T cell clones from normal individuals. We found that in four out of six donors this subset contains expanded clones that often account for 0.5% and, in one individual, even 7% of all peripheral blood lymphocytes. By combining limiting dilution analysis and N region oligotyping of polymerase chain reaction amplified TCR cDNA, we could measure the clonal size and show that two of these expanded clones remain stable in size for up to 4 yr in peripheral blood. The expanded clones analyzed ex vivo are not cycling and CD45 RAhi ROlo, but express high levels of alpha 4/beta 1 integrins, suggesting that they may have reverted to resting cells after activation. One of these expanded DN clones proliferates in vitro in response to Escherichia coli presented by monocytes cultured in GM-CSF plus IL-4 and kills CD1a+ Molt-4 cells. In contrast to what was found in the alpha/beta DN subset, alpha/beta CD4+ T cell clones specific for a tetanus toxin epitope showed a very small clonal size (< 1 in 10(7)) and could not be reisolated after 2 yr. Taken together, these results indicate that large clonal size and persistence are distinctive features of alpha/beta DN cells specific for bacterial antigens. These cells may use antigen-presenting cells, restriction molecules, and selection routes different from those used by antigen-specific CD4+ T cells.

Inhaled nitric oxide versus aerosolized iloprost in secondary pulmonary hypertension in children with congenital heart disease: vasodilator capacity and cellular mechanisms.

BACKGROUND: Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each. METHODS AND RESULTS: A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng. kg(-1). min(-1) for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48+/-0.38 to 0.27+/-0.16 (P:<0.001). Similarly, iloprost decreased the ratio from 0.49+/-0.38 to 0.26+/-0.11 (P:<0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6+/-11.9 to 34.7+/-21.4 nmol/L during iNO (P:<0.01), and plasma cAMP increased from 55.7+/-22.9 to 65.1+/-21.2 nmol/L during iloprost inhalation (P:<0.05). CONCLUSIONS: In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.

Conduction disturbances after correction of tetralogy of Fallot: are electrophysiologic studies of prognostic value?

Late complete heart block may occur after correction of tetralogy of Fallot. Whether postoperative electrophysiologic studies can identify patients at risk of developing this conduction disturbance is unknown. In this study, 57 children who underwent electrophysiologic investigation after correction of tetralogy of Fallot were followed up for 1 to 13 (mean 6.5) years after the investigation. One late death and two cases of late complete heart block occurred. The late death was due to ventricular arrhythmia and not to a conduction disturbance. The cases of late heart block occurred 2 and 5 years, respectively, after electrophysiologic study, and in both cases the patient had a prolonged HV interval; in one patient progressive lengthening of the HV interval could be demonstrated at two subsequent studies 1 year apart. Another five patients with a prolonged HV interval had normally conducted sinus rhythm up to 11 years after study. Atrial pacing at increasing rates (up to the occurrence of second degree atrioventricular block) during electrophysiologic study was the best means of predicting late heart block: of three patients with block below the bundle of His occurring at pacing rates less than 180/min, two developed late complete heart block. Thus, electrophysiologic testing of the conduction system after correction of tetralogy of Fallot is useful in predicting late complete heart block and should be performed in patients with a history of transient heart block after surgery and in those with a prolonged PR interval.

Atrial natriuretic factor in patients with congenital heart disease: correlation with hemodynamic variables.

To investigate the alpha-atrial natriuretic factor in congenital cardiac malformations, three groups of children, aged 7 months to 16 years, with different hemodynamic situations were studied during routine cardiac catheterization. Twenty-one (group I) had tetralogy of Fallot, 24 (group II) had a left to right shunt with pulmonary hypertension and 12 (control group) had a minor cardiac lesion. Alpha-atrial natriuretic factor levels were determined by a radioimmunoassay on blood samples from the inferior vena cava, right atrium, pulmonary artery, left atrium and aorta. To evaluate the effect of an acute volume load, measurements of hormone and pressures were repeated after right ventriculography. Alpha-atrial natriuretic factor levels varied over a wide range in all groups and in all chambers investigated. Nevertheless, children with pulmonary hypertension had significantly higher levels of the hormone (p less than 0.01) and were well separated from the control group, but less well from those with tetralogy of Fallot. A 50% increase of alpha-atrial natriuretic factor from the inferior vena cava to the right atrium occurred in patients with shunt lesions with pulmonary hypertension and in patients with tetralogy of Fallot (p less than 0.001) and a further 30% increase from the right atrium to the pulmonary artery (p less than 0.05). After right ventriculography, a 100% to 200% increase of alpha-atrial natriuretic factor was observed in the total sample (p less than 0.001). A positive correlation was observed between right atrial mean pressure and right atrial alpha-atrial natriuretic factor (r = 0.63) and between pulmonary artery mean pressure and pulmonary artery alpha-atrial natriuretic factor (r = 0.61).(ABSTRACT TRUNCATED AT 250 WORDS)

Sinus node function and conduction system before and after surgery for secundum atrial septal defect: an electrophysiologic study.

Arrhythmias are common in the natural history as well as in the late postoperative course of patients with atrial septal defect (ASD); electrophysiologic disturbances may result from the ASD itself or from surgery. Electrophysiologic studies were performed in 18 children (mean age 10 years) both before and after surgical closure of the ASD. Sinus node (SN) function, conduction intervals and refractory periods (atrial and atrioventricular [AV] nodal) were determined. Before surgery, corrected SN recovery time was prolonged in 14 patients; the mean value for the group was 357 +/- 163 ms. The AH interval was slightly prolonged, as were AV nodal refractory periods. Postoperatively, SN recovery time decreased in all patients who remained in sinus rhythm (p less than 0.02), but 5 patients had atrial ectopic rhythm. The AH interval decreased significantly (p less than 0.02), as did the refractory periods, mainly for the AV node (p less than 0.01). The pacing rate at which second-degree AV block occurred increased. Thus, closure of ASD improves AV conduction, decreases AV nodal refractory periods and improves SN function, probably by suppressing rightsided heart volume overload. However, SN function may be lost, probably as a result of the operative procedure.

Electrophysiologic effects of intravenous verapamil in children after operations for congenital heart disease.

To assess the effect of verapamil in children with congenital heart disease after surgical correction, an electrophysiologic study was undertaken in 19 patients, 0.8 to 15 years old. Atrial pacing and programmed atrial extrastimulation were performed before and 5 mn after intravenous administration of verapamil. A significant increase in conduction time and refractory periods was observed at the atrioventricular node level. Dual or accessory atrioventricular pathways, present in 14 cases, appear to have been suppressed in 9. The effect on the sinus node was of particular interest: The corrected sinus node recovery time was strongly prolonged by verapamil in 6 patients, 5 of whom had undergone surgery with extensive atrial reconstruction (Senning 2, anomalous pulmonary venous return 3) and 1 of whom had undergone correction of tetralogy of Fallot. Additional effects of verapamil were the disappearance of a sinus node entrance block in 8 patients and emergence of an ectopic pacemaker in 6. Although verapamil has electrophysiologic properties that should make it a useful drug in the treatment of reentry tachycardia, caution is indicated after extensive atrial surgery because sinus node depression may occur.

Frequency of ventricular late potentials and fractionated right ventricular electrograms after operative repair of tetralogy of Fallot.

This study was conducted to assess the incidence of abnormalities of ventricular depolarization in sinus rhythm after repair of tetralogy of Fallot and their relation to spontaneous ventricular arrhythmias. Forty-four patients were studied, 10 before surgery (mean age 6.9 years) and 34 after repair (mean age 8.1 years, mean age at surgery 6.5 years, mean interval between surgery and evaluation 11 months). Evaluation was performed by means of body surface and intracavitary signal-averaging techniques, by recording local right ventricular (RV) electrograms at several sites and by 24-hour Holter monitoring (n = 28). No electrophysiologic abnormality was observed in children before surgery. Ventricular late potentials were detected in 18 patients (53%) after repair. Body surface detection of ventricular late potentials was frequently masked by the postoperative right bundle branch block pattern. Local RV electrograms were fractionated in 11 cases (32%) (mean duration 103 +/- 33 ms), most often in the RV outflow tract (n = 9), but no relation was found between fragmentation of RV electrograms and the presence of ventricular late potentials. Spontaneous ventricular arrhythmias occurred in 12 children after repair (43%), but were complex in only 4 patients (14%). There was no correlation between spontaneous ventricular arrhythmias and the presence of ventricular late potentials, presence of fractionated RV electrograms, presence of a proximal right bundle branch block or postoperative hemodynamic status.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular late potentials and induced ventricular arrhythmias after surgical repair of tetralogy of Fallot.

Ventricular tachycardia (VT) and sudden death are rare but recognized complications after surgical repair of tetralogy of Fallot. We prospectively studied 31 patients (19 boys and 12 girls, mean age +/- standard deviation 7 +/- 4 years) with postoperative tetralogy of Fallot, by means of right-sided cardiac catheterization, 24-hour Holter monitoring, body-surface and intracavitary signal-averaging (gain 10(5) to 10(6), filters of 100 and 300 Hz) and programmed ventricular stimulation (1 and 2 extrastimuli, 3 basic cycle lengths, right ventricular apex and outflow tract). All patients were asymptomatic and none had documented or suspected ventricular arrhythmias. Ventricular late potentials were detected in 10 of 31 patients (32%) and spontaneous ventricular arrhythmias in 12 of 31 patients (39%). No sustained VT was induced by programmed ventricular stimulation but nonsustained VT was induced in 3 patients (10%). Patients with inducible VT more often had late potentials (3 of 3 vs 7 of 28, p less than 0.01), and spontaneous ventricular premature complexes (VPCs) during Holter monitoring (3 of 3 vs 9 of 28, p less than 0.05). To predict VT inducibility, late potentials had a sensitivity of 100%, a specificity of 75%, a positive predictive value of 30% and a negative predictive value of 100%. For spontaneous VPCs, the figures were 100, 68, 25 and 100%, respectively. It is concluded that shortly after repair of tetralogy of Fallot, the presence of both spontaneous VPCs and ventricular late potentials are associated with an increased incidence of inducible VT. Conversely, the absence of VPCs and ventricular late potentials may identify patients at low risk of subsequent ventricular arrhythmias.

Inhaled nitric oxide to test the vasodilator capacity of the pulmonary vascular bed in children with long-standing pulmonary hypertension and congenital heart disease.

Nitric oxide-induced vasodilator capacity greatly varies among children with pulmonary hypertension and elevated vascular resistance. The decline of this selective response seems to parallel the progression of established vascular disease and thus may be helpful for the selection of patients for operation.

Transcatheter closure of atrial septal defect and patent foramen ovale with ASDOS device (a multi-institutional European trial).

A clinical trial was conducted to assess the feasibility, safety, and efficacy of the atrial septal defect (ASD) occlusion system for transcatheter closure of secundum ASD and patent foramen ovale (PFO) after episodes of cerebral embolism. Occlusion was attempted in 200 patients aged 1 to 74 years (mean 32). The procedure failed in 26 patients (13%); the device was retrieved through a catheter in 20 and through surgery in 6 patients. Procedure-related complications necessitating surgical removal of the device included device embolization in 2, device entrapment within the Chiari network in 1, frame fracture in 1, and perforation of atrial wall in 2. All 6 patients experienced an uneventful postoperative course. An additional 11 patients (6%) underwent surgical removal of the device during follow-up. There were 163 patients (81%) with an implanted ASD occlusion system at follow-up of from 6 to 36 months (mean 17). Thrombus formation around the device was detected by transesophageal echocardiography in 9 patients 1 to 4 weeks after implantation. One of these patients (who had a coagulation factor XII deficiency) suffered a cerebral thromboembolism. Late atrial wall perforation (5, 6, and 8 months after implantation) occurred in 3 adult patients. Infectious endocarditis developed in 2 adult patients (1%). No late device embolization and no atrioventricular valve injury occurred. An asymptomatic device frame fracture was found in 14% and frame deformity in 4% of all patients during the follow-up period of >230 patient-years. Immediately after closure, a moderate/large residual shunt remained in 8% and a small shunt in 29% of patients. After 1 year, a moderate/large shunt was present in 2% and a small one in 26% of patients. During a total follow-up of 49 patient-years, only 1 of 46 patients with PFO had a transient neurologic event after the closure. The study indicates that patients with centrally situated secundum ASD and those with PFO after cerebral embolism can be treated with this system with a high success rate and an acceptable morbidity.

Aneurysm of the left sinus of Valsalva draining into the right atrium.

We report the case of an arteriovenous fistula connecting the aorta to the right atrium, due to a ruptured aneurysm of the left sinus of Valsalva. Clinical, echocardiographic, and angiographic aspects of this unusual lesion are discussed and correlated. Emphasis is put on the diagnostic value of the echocardiogram; a characteristic dense echo parallel to the posterior aortic wall is seen, along with signs of right ventricular volume overload. Combined with the case history and auscultatory finding (a continuous murmur on the right sternal edge), this may lead to the correct diagnosis by noninvasive means.

Systemic-to-pulmonary artery fistula following actinomycosis.

We report a case of pleuropulmonary actinomycosis in a child followed by a most unusual complication: the appearance of a systemic-to-pulmonary artery fistula in the area where the abscess was drained. Fifteen months after successful treatment with penicillin and surgical drainage, a continuous murmur was heard over the scar. Aortic angiography showed multiple connections between the intercostal arteries and the left pulmonary artery through an angiomatous lesion in the left lower lobe. This resulted in a considerable left-to-right shunt. Possible pathogenic mechanisms are discussed.

Congenital intrathoracic left ventricular diverticulum in an adult.

A 53-year-old woman without any risk factors for coronary artery disease was found to have a congenital intrathoracic left ventricular diverticulum with a narrow long connection to the left ventricular cavity. Coronary angiography revealed normal coronary arteries. The diverticulum was resected and showed three normal cardiac layers. This is an extremely rare finding in the adult population.

Chronotropic and inotropic supports are both required to increase cardiac output early after corrective operations for tetralogy of Fallot.

To assess the respective roles of chonotropism, inotropism, and afterload reduction in increasing cardiac index early after corrective operations for tetralogy of Fallot, we measured vascular pressures and cardiac output and evaluated left ventricular dimension changes before and after a 35% rise in heart rate over baseline. This rise was induced by atrial pacing with intact atrioventricular conduction, isoproterenol, or atrial pacing together with dobutamine. With atrial pacing, left ventricular end-diastolic diameter decreased (38.7 +/- 4.3 to 34.2 +/- 5.6 mm, p less than 0.05), the shortening fraction (ratio of the difference between left ventricular end-diastolic and end-systolic diameters to left ventricular end-diastolic diameter) remained constant, and stroke volume index was reduced (28.8 +/- 4.5 to 19.7 +/- 4.6 ml/m2, p less than 0.05). As a result, cardiac index was left unchanged. When dobutamine was added as supplemental inotropic support, left ventricular end-diastolic diameter remained constant, shortening fraction increased (30% +/- 5.4% to 36% +/- 3.3%, p less than 0.05), and cardiac index rose significantly (3.04 +/- 0.61 to 4.18 +/- 0.85 L/min/m2, p less than 0.05). Heart rate acceleration with isoproterenol, combining chronotropism, positive inotropic support, and afterload reduction, slightly increased left ventricular end-diastolic diameter, significantly raised shortening fraction, and markedly enhanced cardiac index (3.03 +/- 0.55 to 4.9 +/- 1.09 L/min/m2). Atrial pacing with intact atrioventricular conduction, as an isolated chronotropic stimulus, is not suited to increase cardiac index early after operations for tetralogy of Fallot unless additional inotropic support is simultaneously provided.

Hemodynamic effect of isoprenaline and dobutamine immediately after correction of tetralogy of Fallot. Relative importance of inotropic and chronotropic action in supporting cardiac output.

In order to compare the effect of isoprenaline and dobutamine immediately after correction of tetralogy of Fallot, 12 randomly selected patients were studied postoperatively. Left ventricular end-diastolic volume, measured preoperatively by means of left ventricular angiograms in eight patients, was decreased to a mean value of 58.6 +/- 5.5 ml/m2 (mean +/- standard error of the mean). Postoperatively, cardiac output was measured by thermodilution before, during, and after infusion of increasing doses of isoprenaline (0.05, 0.1, and 0.2 micrograms/kg/min) and dobutamine (2.5, 5, and 10 micrograms/kg/min) successively given in each patient. Simultaneously, central venous, left atrial, pulmonary arterial, and systemic arterial pressures were recorded. Cardiac index increased significantly in response to all three doses of isoprenaline. Dobutamine produced only a small increase which was not statistically significant. Stroke volume index did not vary significantly with either drug. Consequently, cardiac index was directly related to heart rate. Preload of the left ventricle as well as afterload was significantly reduced (p less than 0.01 and p less than 0.05, respectively) by isoprenaline but not by dobutamine. An increase in left ventricular work index per minute was found with both drugs; however, only with isoprenaline was the increased work accompanied by a significant increase in cardiac index. We conclude that patients with tetralogy of Fallot usually have a small left ventricle which, immediately after correction, reacts to catecholamines by only an insignificant increase in stroke volume index. Consequently, isoprenaline is more effective than dobutamine in raising cardiac index due to the increase in heart rate. Moreover, it decreases systemic vascular resistances and obviates the need for administration of a vasodilator.

Prosthetic heart valve replacement in children. Results and follow-up of 273 patients.

We report the results and long-term follow up in 273 children (aged 2 to 16 years) who underwent prosthetic valve replacement. Mechanical valves (mostly Starr-Edwards) were used in almost all, and in 62 children more than one valve was replaced. Operative mortality was 4.7%. Actuarial survival curves (including hospital mortality) indicate a 86% survival rate at 5 years and 75% at 10 years. For isolated mitral valve prostheses (the largest subgroup), the figures are 87% at 5 years and 82% at 10 and 15 years. The main complication was thromboembolism, which occurred at a linearized rate of 2.7 per 100 patient-years. Actuarial curves indicate that 88% of patients are embolus free at 5 years, and 77% at 10 years. No patient with aortic valve replacement only had an embolism. Five of eight tricuspid prostheses thrombosed. Patients given aspirin and dipyridamole only did not have a higher rate of thromboembolic events than those given warfarin. There were five cases of endocarditis (two fatal) and four of dehiscence. No patient so far has needed replacement of a prosthesis because of somatic growth. Thus valve replacement can be performed with low mortality in children, and with satisfactory long-term survival. Thromboembolism remains a significant problem, although it appears to be less common than in adults. In this study, treatment with antiplatelet drugs only did not carry a higher rate of thromboembolic events than did treatment with warfarin.

Use of Gianturco Z stents in the treatment of vascular compression of the tracheobronchial tree in childhood. A feasible solution when surgery fails.

Severe tracheomalacia secondary to extrinsic vascular compression following a switch operation for transposition is reported. Two attempts at surgical correction failed but successful treatment has been achieved by implantation of two endobronchial Gianturco Z stents. Nonabsorbable stenting in children should be used only in severe obstruction as a last resource, but this technique proved to be feasible in a child weighing 6.2 kg.

Intrathoracic neuroblastoma presenting with neonatal cardiorespiratory distress.

We report an unusual presentation of congenital intrathoracic neuroblastoma. Severe respiratory distress was present at birth and several salient clinical signs were suggestive of neonatal myocarditis. Excessive catecholamine secretions may have caused the observed cardiac dysfunction. Peculiar previously unreported cutaneous lesions were also noted in this case.

Atrial natriuretic factor after heart operations in children. Relation to hemodynamic and renal parameters.

The purpose of this study was to measure changes in serum atrial natriuretic factor concentrations immediately after heart operations in children under baseline conditions and in response to continuous infusion of dopamine (2.5 and 5.0 micrograms/kg/min). During control periods, levels of atrial natriuretic factor were elevated at 190 +/- 24 and 199 +/- 36 pg/ml. The cardiac index was 2.6 L/min/m2 and the renal plasma flow was decreased to 269 +/- 41 ml/min/1.73 m2, indicating a state of renal vasoconstriction (mean renal fraction of cardiac index of 10.0% +/- 1.0%). The mean sodium fractional reabsorption was 99.0% +/- 0.2%. During dopamine infusion, atrial natriuretic factor concentrations increased to 259 +/- 57 pg/ml and to 280 +/- 56 pg/ml, with dopamine 2.5 and 5.0 micrograms/kg/min, respectively (p = not significant), whereas left atrial pressure decreased from 11.7 +/- 0.9 mm Hg during the control period to 10.1 +/- 0.9 and to 9.9 +/- 1.0 mm Hg (p less than 0.05). No correlation was found between changes in left atrial pressure and atrial natriuretic factor levels. Dopamine at 5 micrograms/kg/min increased the cardiac index to 3.0 +/- 0.2 L/min/m2 (p less than 0.001) and the renal plasma flow to 406 +/- 61 ml/min 1.73 m2 (p less than 0.001), alleviating the renal vasoconstriction. The mean urinary sodium excretion increased to 0.33 +/- 0.08 mmol/kg/hr (p less than 0.01). The atrial natriuretic factor plasma concentrations were not related to the urinary sodium excretion, renal plasma flow, or glomerular filtration rate during the control period or during dopamine treatment. These data indicate that after heart operations in children, low urinary sodium excretion occurs despite high circulating atrial natriuretic factor levels. Atrial natriuretic factor concentrations were related neither to left atrial pressures nor to the renal changes induced by dopamine.

Aortic valve repair by cusp extension with the use of fresh autologous pericardium in children with rheumatic aortic insufficiency.

OBJECTIVES: Our goal was to evaluate the midterm results of aortic valve repair by a more sophisticated tailoring of cusp extension-taking into account the dimensions of the native aortic cusps-with the use of fresh autologous pericardium. PATIENTS AND METHODS: Forty-one children who had severe rheumatic aortic insufficiency (mean age 11.5 +/- 2.7 years) underwent aortic valve repair by means of this cusp extension technique over a 5-year period. Twenty-four of them underwent concomitant mitral valve repair for associated rheumatic mitral valve disease. All children were then followed up by transthoracic echocardiography before discharge, at 3 and 6 months after the operation, and at yearly intervals thereafter. RESULTS: Follow-up was complete in all patients and ranged from 3 months to 5 years (median 3 years). No operative and no early postoperative deaths occurred. Only 1 patient died, 9 months after the operation, of septicemia and multiple organ failure. Actuarial survival was 97% at 1 year and has remained unchanged at 3 years. On discharge, the degree of aortic insufficiency was grade 0 for 27 children and grade I for 14. Exacerbation of aortic insufficiency from grade I to grade II was observed in only 1 patient, and none of the children required reoperation for aortic insufficiency during the follow-up period. Mean peak systolic aortic valve gradients at discharge were lower than preoperative values (P =.04), and no significant increase in the peak systolic transvalvular gradient was detected thereafter during the follow-up period. Mean left ventricular dimensions were significantly reduced at discharge when compared with preoperative values (P <.0001). CONCLUSIONS: Functional results of aortic valve repair with cusp extension using fresh pericardium have been satisfactory at medium term, particularly in children with a small aortic anulus at the time of initial repair, because the expansion potential of fresh autologous pericardium is equivalent to that of the growing sinotubular junction and aortic anulus diameters.