Magnetic nanocarriers for the specific delivery of siRNA: Contribution of breast cancer cells active targeting for down-regulation efficiency.

The association between superparamagnetic iron oxide nanoparticles (SPION), carrying small interfering RNA (siRNA) as therapeutic agents and humanized anti- human epidermal growth factor receptor-2 (HER2) single-chain antibody fragments (scFv) for the active delivery into HER2-overexpressing cells appears as an interesting approach for patients with HER2-overexpressing advanced breast cancer. The obtained Targeted Stealth Magnetic siRNA Nanovectors (TS-MSN) are formulated by combining: (i) the synthesis protocol of Targeted Stealth Fluorescent Particles (T-SFP) which form the core of TS-MSN and (ii) the formulation protocol allowing the loading of T-SFP with polyplexes (siRNA and cationic polymers). TS-MSN have suitable physico-chemical characteristics for intravenous administration and protect siRNA against enzymatic degradation up to 24 h. The presence of HER2-targeting scFv on TS-MSN allowed an improved internalization (3-4 times more compared to untargeted S-MSN) in HER2-overexpressing breast cancer cells (BT-474). Furthermore, anti-survivin siRNA delivered by TS-MSN in HER2-negative breast-cancer control cells (MDA-MB-231) allowed significant down-regulation of the targeted anti-apoptotic protein of about 70%. This protein down-regulation increased in HER2+ cells to about 90% (compared to 70% with S-MSN in both cell lines) indicating the contribution of the HER2-active targeting. In conclusion, TS-MSN are promising nanocarriers for the specific and efficient delivery of siRNA to HER2-overexpressing breast cancer cells.

Stealth magnetic nanocarriers of siRNA as platform for breast cancer theranostics.

The endogenous mechanism of RNA interference is more and more used in research to obtain specific down-regulation of gene expression in diseases such as breast cancer. Currently, despite the new fields of study open up by RNA interference, the rapid degradation of siRNA by nucleases and their negative charges prevent them from crossing cell membranes. To overcome these limitations, superparamagnetic iron oxide nanoparticles (SPIONs) represent a promising alternative for nucleic acid delivery. Previously, we reported the magnetic siRNA nanovectors (MSN) formulation using electrostatic assembly of (1) SPIONs, also able to act as contrast agents for magnetic resonance imaging (MRI), (2) siRNA and (3) chitosan aiming at their protection and enhancing their transfection efficacy. However, these nanoparticles displayed low stability in biological suspensions and inefficient transfection of active siRNA. This work aimed at upgrading MSN to Stealth MSN (S-MSN) by adding a polyethylene glycol coating to ensure colloidal stability and stealth properties. Furthermore, another polymer (poly-L-arginine) was added for efficient siRNA transfection and the quantitative composition of the formulation was adapted for biological purposes. Results showed that S-MSN provide high siRNA complexation and protection against enzymatic degradation. Green fluorescent protein (GFP) specific down-regulation on MDA-MB231/GFP cells was comparable to that of commercially available reagents, without observable cytotoxicity. According to our works, S-MSN appears as an effective formulation for in vitro siRNA specific delivery.

[Neonatal cardiac transplantation. Long-term results]. / Transplantation cardiaque néonatale. Résultats à long terme.

The pioneering work of Bailey since 1985 has made cardiac transplantation an effective treatment of left heart hypoplasia in the neonatal period. At the Marie-Lannelongue surgical centre, 5 neonates with hypoplastic left hearts or an equivalent cardiac malformation, underwent cardiac transplantation between 1993 and 1998. There were no operative deaths. At the end of the follow-up, all children were treated with cyclosporine, without steroids. One child died of a secondary acute rejection resistant to treatment 7 years after the transplantation, 1 has a severe coronary problem 13 years after the transplantation, and three children (including the diseased child) have psychomotor development abnormalities. These results and those of the literature together with the psychological problems encountered by the children and their families, do not incite in the pursuit of the neonatal transplantation program until the introduction of new drugs for the treatment of chronic rejection which should prevent the programmed death of these children.

Biventricular repair of transposition of the great arteries and unbalanced ventricles.

BACKGROUND: It is well established that the arterial switch operation is the surgical procedure of choice in patients with transposition of the great arteries and balanced ventricular anatomy. The surgical approach of choice in patients with transposition but unbalanced ventricular size is unknown. OBJECTIVES: Since the beginning of the arterial switch operation program, patients with transposition of the great arteries and unbalanced ventricles underwent biventricular repair by means of the arterial switch operation and repair of any associated lesions, either through a single or staged surgical procedure. The aim of this retrospective study is to analyze whether this approach can be proposed to such patients. METHODS: Forty-four patients with transposition of the great arteries and unbalanced ventricles underwent this surgical approach since 1984. Two groups were defined: group I had transposition with a dominant right ventricle (n = 28), and group II had transposition with a dominant left ventricle (n = 16). In group I the median age and weight at the arterial switch operation were 8.5 days (range, 5-70 days) and 3.1 kg (range, 1.5-3.7 kg), respectively. The median end-diastolic left ventricular volume, mass, and long-axis ratio were 15 mL/m2 (range, 11-16 mL/m2), 31.5 g/m2 (range, 20-66 g/m2), and 0.85 (range, 0.9-0.7), respectively. The mitral valve diameter was slightly hypoplastic, with a median z value of -1.22 (range, -0.3 to 3.7). In group 2 the median age and weight at the arterial switch operation were 42 days (range, 8 days-15 years) and 3.5 kg (range, 2.8-35 kg), respectively. Associated lesions in this group were coarctation in 9 and single (n = 12) or multiple (n = 4) ventricular septal defects. The median long-axis ratio and tricuspid z value were 0.6 (range, 0.3-0.8) and -0.9 (range, -0.5 to 3.3), respectively. In this group 9 patients had a single-stage procedure with fenestrated ventricular defect patches, atrial septal defect patches, or both; 7 patients underwent the staged approach. RESULTS: In group I there was 1 early death from sepsis after weaning from postoperative extracorporeal membrane oxygenation. Three patients had severe pulmonary hypertension, one of whom died 1 year later. All survivors demonstrated, at discharge from the hospital, equilibrated ventricular size, with a median left ventricular end-diastolic volume of 25 mL/m2 (range, 21-30 mL/m2). In group II there were 2 early and 1 late deaths. All early deaths occurred in patients without voluntary residual intracardiac shunts. Median early postoperative long-axis ratio and tricuspid z value were 0.8 (range, 0.7-1) and -0.2 (range, 0.74 to 1.2), respectively. CONCLUSION: This study demonstrates that the arterial switch operation in patients with transposition of the great arteries and unbalanced ventricles remains a good surgical option.

[Enlarging angioplasty of the aortic arch with an pulmonary artery autograft patch. Interest in a single-stage repair of the syndrome of coarctation and interruption of the aortic arch]. / Angioplastie d'agrandissement de la crosse aortique par un patch d'autogreffe pulmonaire. Intérêt dans la réparation en un temps des syndromes de coarctation et interruption de l'arche aortique.

Single stage repair of syndromes of coarctation and interruption of the aortic arch is a routine procedure in many surgical centres with good immediate results. The classical technique of aortic repair is based on the principles of Crafoord's extended resection anastomosis. Recoarctation is not an unusual long-term complication. A technique of enlarging angioplasty of the aorta using a patch of pulmonary artery has been developed and used in 22 neonates with obstruction of the aortic arch associated with ventricular septal defect with an average age and body weight of 15 days and 2.9 Kg respectively. The ventricular septal defect was closed surgically during the same procedure. Total circulatory arrest was not used in these children and all had aortic repairs with selective cerebral perfusion with moderate hypothermia (28-30 degrees C). This technique was used without any procedure-related early morbidity. No early or late deaths were observed in this series. Two patients were reoperated during the first year after the initial procedure: one for residual ventricular septal defect and the other for supraventricular pulmonary stenosis. Two patients, one of whom was reoperated, developed supraventricular pulmonary stenosis with a gradient of over 60 mmHg. These stenoses were observed in the first cases operated and were essentially due to the technique of pulmonary artery reconstruction. Over a median follow-up period of 10 months, no recoarctations were observed: the Doppler ultrasound study showed an isolated mean systolic gradient of 6 +/- 12 mmHg. The authors conclude that angioplasty of the aortic arch with an enlarging patch of pulmonary artery autograft during single stage surgery of syndromes of coarctation and interruption of the aortic arch provides a harmonious and durable repair of the aortic arch.

[Ross mitral procedure for massive congenital mitral insufficiency]. / Intervention de Ross mitral pour une insuffisance mitrale massive congénitale.

The authors report the case of a 4 month old North African baby with massive congenital mitral insufficiency associated with a coarctation of the aorta. The surgical treatment consisted in correction of the coarctation followed, several days later, by a Ross mitral procedure after failure of mitral reconstructive surgery. The postoperative course required circulatory assistance for 4 days and the child returned to his family two months after surgery. Control echocardiography before hospital discharge showed good function of the pulmonary autograft in the mitral position with no regurgitation but slight stenosis with a mean transvalvular pressure gradient of 4 mmHg. This procedure may be used in certain cases as an alternative to mitral valve replacement.

Surgical management of transposition of great arteries associated with multiple ventricular septal defects.

OBJECTIVE: The presence of associated multiple ventricular septal defects (VSDs) increases the risk of the anatomic repair for transposition of the great arteries (TGA). The aim of this study was to define the optimal management of this complex anomaly. METHODS: Between January 1988 and December 1998, 45 patients underwent anatomic repair of TGA associated with multiple VSDs. The median age was 50 days and the median weight 4 kg. Eighteen (40%) had undergone previous palliation including 17 pulmonary artery banding procedure (PAB), seven associated with coarctation repair and one isolated coarctation repair. The perimembraneous septum was involved in 24 patients, the trabecular in 43, the inlet in seven and the infundibular in two. Closure of the VSDs included Dacron or pericardial patchs and matress sutures. The initial approach was through right atriotomy which was sufficient in 15 patients. VSDs were closed through right ventriculotomy in 13 patients, through pulmonary artery in six, through the aorta in one and in the remaining (n = 10) combined approaches were used. Only one patient required left apical ventriculotomy. RESULTS: There were five hospital deaths (11%; 70% CL: 6-18%) including the one early reoperation for residual VSD closure. Five patients had successful early reoperation for secondary PAB for residual VSD. Three late deaths occurred (7%; 70% CL: 3-13%). At the last visit, 95% of survivors were asymptomatic and without any cardiac medication. CONCLUSION: Mid-term survival with good quality of life can be achieved following either one or two-stage repair of this complex anomaly. In the presence of VSD closure failure a secondary PAB may be the procedure of choice.

[Biventricular repair in neonates with hypoplasia of the left ventricle]. / Réparation biventriculaire chez les nouveau-nés ducto-dépendants avec hypoplasie relative des cavités gauches.

BACKGROUND: Whether to perform uni or biventricular repair in ducto dependent neonates with hypoplastic but morphologically normal left ventricle and multi level left ventricle obstructions (hypoplastic left heart syndrome class III) remains unanswered. Echocardiographic criteria have been proposed for surgical decision. HYPOTHESIS: Increased afterload and multi level left ventricle obstruction is constant. We assumed that restoration of normal loading conditions by relief of left ventricle obstructions promotes its growth, provided that part of the cardiac output was pre operatively supported by the left ventricle, whatever the echocardiographic indices. METHODS: Twenty one ducto dependent neonates presented with this anomaly. All had aortic coarctation associated to multi level left ventricle obstruction. Pre operative echocardiographic assessment showed: mean end diastolic left ventricular volume of 13.3 +/- 3.5 mL/m2 and mean Rhodes score of -1.43 +/- 0.9. Surgery consisted in relief of left ventricle outflow tract obstruction by coarctation repair in 21 associated to atrial septal defect closure in 2, aortic commissurotomy in 1 and ascending aorta enlargement in 1. RESULTS: There were 3 early and 3 late deaths. There was no predictive risk factor for failure. Growth of the left heart was demonstrated in most patients. At hospital discharge the end diastolic left ventricular volume was 19.4 +/- 3.12 mL/m2 (p = 0.0001) and the Rhodes score was -0.38 +/- 1.01 (p = 0.0003). Actuarial survival and freedom from reoperation rates at 5 years were: 68.5% and 40.75%, respectively. CONCLUSION: Biventricular repair can be proposed to ducto dependent neonates with hypoplastic but morphologically normal left ventricle provided that all anatomical causes of left ventricle obstruction can be relieved. Secondary growth of the left heart then occurs, however the reoperation rate is not low.

Biventricular repair approach in ducto-dependent neonates with hypoplastic but morphologically normal left ventricle.

OBJECTIVES: Increased afterload and multilevel LV obstruction is constant. We assumed that restoration of normal loading conditions by relief of LV obstructions promotes its growth, provided that part of the cardiac output was preoperatively supported by the LV, whatever the echocardiographic indexes. BACKGROUND: Whether to perform uni- or biventricular repair in ducto dependent neonates with hypoplastic but morphologically normal LV (hypoplastic left heart syndrome classes II & III) remains unanswered. Echocardiographic criteria have been proposed for surgical decision. METHODS: Twenty ducto dependent neonates presented with this anomaly. All had aortic coarctation associated to multilevel LV obstruction. Preoperative echocardiographic assessment showed: mean EDLW of 12.4 +/- 3.03 ml/m2 and mean Rhodes score of -1.73 +/-0.8. Surgery consisted in relief of LV outflow tract obstruction by coarctation repair in all associated to aortic commissurotomy in one and ASD closure in 2. RESULTS: There were 3 early and 2 late deaths. Failure of biventricular repair and LV growth was obvious in patients with severe anatomic mitral stenosis. The other demonstrated growth of the left heart. At hospital discharge the EDLVV was 19.4+/-3.12 ml/m2 (p = 0.0001) and the Rhodes score was -0.38+/-1.01 (p = 0.0003). Actuarial survival and freedom from reoperation rates at 5 years were 72.5% and 46%, respectively. CONCLUSIONS: Biventricular repair can be proposed to ducto dependent neonates with hypoplastic but morphologically normal LV provided that all anatomical causes of LV obstruction can be relieved. Secondary growth of the left heart then occurs; however, the reoperation rate is high.

Surgical management of progressive pulmonary venous obstruction after repair of total anomalous pulmonary venous connection.

BACKGROUND: The occurrence of a progressive pulmonary venous obstruction after the repair of the total anomalous pulmonary venous connection is a severe complication. OBJECTIVES: The objectives of this study were to retrospectively review the patients with this condition and to report our experience with a new surgical technique with a sutureless in situ pericardium repair. METHODS: Of 178 patients who underwent correction of total anomalous pulmonary venous connection, 16 patients (9%) experienced the development of a progressive pulmonary venous obstruction in a median interval of 4 months (5 weeks-12 years). Three patients had isolated anastomotic stenosis, 4 patients had isolated pulmonary venous ostial stenosis, and 9 patients had both. Pulmonary venous obstruction was bilateral in 7 patients. The surgical procedures used at reoperation included 8 patch enlargements, 5 ostial endarterectomies, 1 intraoperative stenting, and 7 sutureless in situ pericardium repairs. RESULTS: There were 4 deaths after reoperation (4 of 15 patients; 27%). The only significant mortality risk factor was the bilateral location of the pulmonary venous obstruction (P =.045). In patients with isolated anastomotic stenosis or with only 1 pulmonary venous ostial stenosis (n = 5), there was no death, except the patient presenting with a single ventricle. In patients with 2 or more pulmonary venous ostial stenoses (n = 10), there were 3 deaths; 5 of the 7 survivors were successfully treated with the in situ pericardial technique, with normalized pulmonary artery pressure at a mean follow-up of 26 months. CONCLUSION: Progressive pulmonary venous stenosis after repair of total anomalous pulmonary venous connection remains a severe complication when bilateral. The sutureless in situ pericardial repair offers a satisfactory solution, particularly on the right side.

Biventricular repair for double-outlet right ventricle. Results and long-term follow-up.

BACKGROUND: The purpose of the present study was to define the optimal management and to identify the risk factors for death and repeat operation in patients with double-outlet right ventricle. METHODS AND RESULTS: From 1985 through 1996, 154 consecutive patients underwent biventricular repair for double-outlet right ventricle. The presence of bilateral infundibular structures was the major inclusion criteria (142 patients). According to the relationship of the ventricular septal defect (VSD) to the great arteries, there were 86 patients with a subaortic VSD (56%), 45 patients with a subpulmonary VSD (29%), 18 patients with a noncommitted VSD (12%), and 5 patients with a doubly committed VSD (3%). Sixty-five patients (42%) had undergone previous palliative procedures. At repair, the median age was 10 months, and the median weight was 6.5 kg. Two main types of repair were used: intraventricular baffle repair (n = 115) and arterial switch operation with VSD-to-pulmonary artery baffle (n = 39). There were 14 hospital deaths (9%; 70% confidence limit [CL], 7% to 12%). The only significant risk factor for early death was the presence of congenital mitral valve anomalies (P = 0.02). Twenty-eight patients (18%) required 39 repeat operations. The repeat operation rate was higher in patients with associated VSD enlargement at baffle construction (n = 29; 19%) (P = 0.01). There were 6 late deaths (4%; 70% CL, 2% to 7%). Patients presenting with pulmonary stenosis constituted a low-risk group for global death (P = 0.008). The median follow-up was 52 months. Ten-year actuarial survival and survival with freedom from repeat operation rates were 86% and 62% (70% CL, 83% to 89% and 54% to 70%), respectively. CONCLUSIONS: Long-term survival with good quality of life can be achieved after either 1- or 2-stage repair of this complex anomaly.

Tracheoplasty in congenital tracheal stenosis.

Congenital tracheal stenosis is an uncommon but life-threatening condition whose management is still debated. The rarity of this disease explains the lack of a standard management. Between 1986 and 1996, eight children younger than 1 year were referred to our Institution with a tracheal stenosis. The median age at operation was 3.15 months and the median weight was 4.5 kg. The diagnosis was made after an episode of respiratory distress in all but one and was confirmed by fiberoptic bronchoscopy. The median length of tracheal stenosis was 24.5 mm (Ranges: 4-30 mm). Only one patient was free from associated cardiovascular defect. Tracheal repair was performed under cardiopulmonary bypass in all. In three it was achieved by pericardial augmentation of the stenosed area, in four by resection and end to end anastomosis and in one by sliding tracheoplasty. Concomitant cardiac repair was performed in six. Two patients died after pericardial patch augmentation. In both, death was related to profound hypoxemia due to patch collapse. Two patients developed restenosis after resection and end to end anastomosis. They both had stent placement and one required reoperation and underwent a sliding tracheoplasty. At a median follow-up of 21 months (Ranges: 6-120) all the survivors are doing well and are free from respiratory symptoms. Bronchoscopic evaluation revealed in all a widely patent anastomosis without restenosis. In conclusion, tracheal stenosis in children remains a challenging lesion. Surgical technique, whether resection and end to end anastomosis or sliding tracheoplasty offer better results and should be discussed according to the length of the stenosis. Pericardial plasty should be used with caution.

Two-stage correction of transposition of great arteries with complete atrioventricular canal.

We report a successful two-stage anatomic correction of D-transposition of the great arteries associated with complete atrioventricular canal without pulmonary obstruction, combining an arterial switch procedure and a two-patch repair for complete atrioventricular canal, after pulmonary artery banding in the neonatal period.

[Anatomical repair in transposition of great vessels]. / La réparation anatomique de la transposition des gros vaisseaux.

Transposition of the great arteries (TGA) covers a wide range of anatomic variants involving not only the origin of the great arteries, but the intracardiac structures and the aortic arch. TGA can now benefit from complete anatomic repair, namely switch operation, performed in simple forms during the neonatal period. Accurate pre and intraoperative assessment must take into account the main anatomic features: relationship between the aorta and the pulmonary artery and coronary arteries distribution. Over the last sixteen years, 1,063 patients with TGA underwent anatomic repair in our institution. Among 728 patients with simple TGA, 92% were operated on within the first 2 weeks of life. Among 335 patients with complex TGA, all had a large VSD and 154 had additional anomalies. Among these 335 patients, 264 had one-stage complete repair and 71 had two-stage repair, at the beginning of our experience. In complex forms the main associated anomalies involved the ventricles (right ventricle hypoplasia (11), malaligned VSD (90), restrictive VSD (3), multiple VSD (43), the atrioventricular valves (straddling of the mitral or tricuspid valve (15), mitral valve anomalies (cleft or tissue tag, 4) and the aortic arch (coarctation [88], interrupted aortic arch (8)). The hospital mortality was 6.9% for simple TGA, 14.6% for complex TGA. Main causes of early death were failure in coronary artery relocation and pulmonary hypertensive crisis. Mean follow-up (95.5% of patients) was 49 months. Overall 16-year survival was 87.9%, 91.5% for simple forms and 80.4% for complex forms. Anatomic repair is nowadays the treatment of choice for TGA. Long-term results will depend on the evolution of the relocated coronary arteries and of the neo-aortic valve.

Biventricular repair of conotruncal anomalies associated with aortic arch obstruction: 103 patients.

BACKGROUND: Biventricular repair of conotruncal anomalies associated with aortic arch obstruction is a complex surgical procedure that combines a cardiac repair and a aortic arch reconstruction. METHODS AND RESULTS: From January 1984 to April 1996, such a repair was performed in 103 patients. The conotruncal anomalies included: 15 transpositions of the great arteries (TGAs) with intact ventricular septum, 44 TGAs with ventricular septal defect, 32 double outlet right ventricle with subpulmonary ventricular septal defect, 10 truncus arteriosus, one double outlet left ventricle, and one tetralogy of Fallot. The arch obstruction included 88 coarctation and 15 interrupted aortic arch. One-stage repair has been the favored technique since 1990 and was performed in 58 neonates, including 38 TGAs or double outlet right ventricle and ventricular septal defect, 10 TGAs with intact ventricular septum, and all of the 10 truncus arteriosus. The cardiac repair included 89 arterial switch operations, 2 Kawashima rerouting, 10 truncus arteriosus repairs, and one double-outlet left ventricle repair and one tetralogy of Fallot repair. The aortic arch was reconstructed by direct anastomosis in 85 patients, with a Gore-Tex conduit in three patients and more recently by an ascending aortic patch augmentation in 15 patients. The hospital mortality was 12% (7 of 58) for the one-stage repair and 20% (9 of 45) for the two-stage repair. There were six late deaths. Reoperations or angioplasties were mandatory for 12 right ventricle outflow tract obstructions after arterial switch, involving 10 patients with double outlet right ventricle (P=.02), 10 recurrent arch obstruction, and six miscellaneous lesions. CONCLUSIONS: One-stage biventricular repair of conotruncal anomalies associated with aortic arch obstruction can be achieved in selected patients with an 83% survival rate at 7 years.

Prevention of unbalanced lung perfusion and atrial arrhythmias after the lateral tunnel operation.

BACKGROUND: The lateral tunnel operation has become increasingly popular with pediatric cardiac surgeons, as it is technically reproducible, is relatively easy to perform, and can be used in a variety of patients with single-ventricle physiology. The main drawbacks of the original operation are uneven blood flow distribution to the lungs and increasing incidence of supraventricular arrhythmias over time. METHODS: In 1988, we modified this technique by avoiding narrowing of the tunnel at the superior vena cava-atrial junction, avoiding incorporation of the crista terminalis in the baffle suture line, and minimizing damage to the sinoatrial node. Between 1988 and 1995, 19 patients underwent this operation at Marie-Lannelongue Hospital in Paris. RESULTS: There was one early death and no late deaths. At a mean follow-up of 5.2 years, all survivors are in New York Heart Association class I. Early atrial flutter, related to atrial scarring secondary to multiple previous surgical procedures, developed in 1 patient, and late atrial flutter developed in 1 patient who had a previous Blalock-Hanlon atrial septectomy. All patients are currently in sinus rhythm. Atrial flutter did not occur in 17 patients who had had no previous atrial wall surgical procedure. CONCLUSIONS: We believe that the good long-term clinical results are directly attributable to our modifications, which ensure optimal hemodynamics and absence of rhythm disturbances. All patients who had not previously undergone operation on the atrial wall were free from supraventricular tachyarrhythmias at a mean follow-up of 5.2 years. This is a consequence of protecting the sinus node, crista terminalis, and Bachmann's bundle.

Endogenous nitric oxide production and atrial natriuretic peptide biological activity in infants undergoing cardiac operations.

OBJECTIVES: To examine whether preoperative heart failure and cardiac surgery influence nitric oxide production and atrial natriuretic peptide (ANP) biological activity in infants and whether nitric oxide and ANP participate in the control of postoperative pulmonary vascular tone. DESIGN: Prospective, clinical study. SETTING: Tertiary pediatric cardiac intensive care unit in a referral cardiosurgical center. PATIENTS: Nineteen infants (median age 4 months) undergoing cardiac surgery: 13 infants with ventricular or atrioventricular septal defect associated with heart failure and pulmonary hypertension (group 1); and six infants with tetralogy of Fallot, without heart failure (group 2). INTERVENTIONS: Blood samples obtained from indwelling catheters or bypass circuit outlets. MEASUREMENTS AND MAIN RESULTS: Nitrite and nitrate blood concentrations (as a marker for nitric oxide synthesis) and the molar ratio of cyclic guanosine 3',5'-monophosphate (cGMP) to ANP (as a marker for ANP biological activity) were determined before, during, and up to 24 hrs after cardiopulmonary bypass (CPB). In group 1 patients, these biological parameters were related to postoperative pulmonary arterial pressure. Preoperative nitrite and nitrate concentrations were higher in group 1 patients than in group 2 patients (p < .02), and this difference persisted during CPB. Nitrite and nitrate concentrations 24 hrs postoperatively were lower than preoperative values in group 1 patients (p < .05) and were unchanged in group 2 patients. An inverse correlation was observed postoperatively between nitrite and nitrate concentrations and systolic pulmonary arterial pressure (r2 = 0.4, p < .05). Group 1 patients had a lower preoperative cGMP/ANP ratio than group 2 patients (p < .05), despite higher ANP levels (p < .005). The cGMP/ANP ratio decreased during CPB in both groups (p < .0001), and in group 2 patients, cGMP and ANP values remained below preoperative values < or = 24 hrs postoperatively. A correlation was observed between ANP levels and systolic pulmonary arterial pressure 2 and 4 hrs postoperatively (r2 = .4, p < .05, respectively), but no correlation was observed between ANP biological activity and postoperative pulmonary arterial pressure. CONCLUSIONS: Infants with heart failure and pulmonary hypertension have increased nitric oxide synthesis and decreased ANP biological activity; both phenomena may be involved in the pathophysiology of this clinical condition. CPB has no detectable effect on nitric oxide production but does decrease ANP biological activity. In patients with preoperative heart failure and pulmonary hypertension, endogenous nitric oxide appears to play a role in the control of postoperative pulmonary vascular tone.

Technique to repair tetralogy of Fallot with absent pulmonary valve.

The syndrome of tetralogy of Fallot with absent pulmonary valve is characterized by aneurysmal dilatation of the pulmonary arteries causing tracheobronchial obstruction of varying degree. Relief of this obstruction is the main goal of the surgical repair and can best be achieved by appropriate pulmonary arterioplasty. We describe our current technique to repair this syndrome in infants and older children including pulmonary arterioplasty, ventricular septal defect closure, and right ventricular outflow tract reconstruction without valve insertion.

Surgical management of atrio ventricular septal defects with normal caryotype.

OBJECTIVE: Atrio ventricular septal defects (AVSD) with normal caryotype represent in average 25% of AVSD. They constitute a more complex group of patients characterized by frequent left sided heart obstructive lesions, raising the problem of the appropriate indications between biventricular and univentricular procedures. METHODS: Sixty-nine consecutive patients, who had AVSD with normal caryotype underwent surgery. According to the anatomical complexity there were 22 intermediate AVSD, 36 complete AVSD and 11 complex AVSD. Associated lesions were present in 68% of the patients including left sided heart anomalies in 57%. According to the size of the left ventricle (LV) evaluated on the LV/RV end diastolic diameter ratio calculated at 2D echocardiogram: right ventricular (RV) dominance was found in 29%; with border line LV in 13 patients and truly hypoplastic LV in 7 patients. Biventricular repair was always favored in case of border line LV and precluded when the LV/RV ratio was less than 0.33. RESULTS: There were 57 biventricular repairs with 10 years actuarial survival of 70 +/- 8% and respectively, 100% in the complex AVSD, 86% in the intermediate AVSD and 51% in the complete AVSD (P = 0.006). The risk factors for biventricular repair were the association to a subaortic stenosis (P = 0.01) and the severity of the mitral valve lesions (P = 0.03) that led to 38% reoperation. There were 12 univentricular palliation with 10 years survival of 66 +/- 14%. The risk factor for univentricular palliation was the association to a severe pre-operative mitral regurgitation (P = 0.005). CONCLUSIONS: Biventricular repair should be precluded in patients presenting with subaortic stenosis. Severe mitral valve anomalies lead to elevated mortality and morbidity with frequent reoperations. Univentricular repair might have larger indications and cardiac transplantation might be considered in patients with truly hypoplastic LV presenting with severe pre-operative AV valve regurgitation.