Socio-demographic parameters and non-cardiac comorbidity related to self-perceived quality of life in young adults after neonatal arterial switch operation for transposition of the great arteries.

Evaluating the relation of non-cardiac comorbidity and socio-demographic factors to physical and mental health-related quality of life (QOL) which has been partially found at elevated risk in young adults after neonatal arterial switch operation (ASO) for transposition of the great arteries (TGA). In a prospective reassessment study, results of 92 unselected young adults (22.8 ± 2.6 years) having undergone evaluation of QOL (SF-36) were related to non-cardiac comorbidity with special respect to neurologic and psychiatric comorbidity and to socio-demographic parameters. Neurologic (14%) contrary to psychiatric comorbidities (6.5%) were more frequent than in the general population. The educational level was higher, the rate of unemployment was double as high compared to the average German population. Significant inverse relations (p = 0.006 to 0.033) existed between physical health domains (physical functioning and general health perception) and non-cardiac, neurologic, and psychiatric comorbidity, as well as correlations between the latter domains and socio-economic status, educational level, and worse employment status (Spearman 0.22-0.41, p < 0.0001 to 0.036). Mental health domains (vitality, social functioning, psychical health) were significantly inversely related with neurologic and psychiatric comorbidity (p = 0.002 to 0.048) and correlated with higher educational level (Spearman 0.25, p = 0.019). Neurologic and psychiatric comorbidities and socio-demographic parameters are significant risk factors for a reduced QOL concerning physical and mental health in young adults with TGA after ASO. Standardized QOL measurement should be part of routine screening programs to detect subclinical physical, neurodevelopmental, and psychosocial comorbidity.

The association of bicuspid aortic valve on long-term outcome following one-stage repair of aortic arch obstruction associated with ventricular septal defect.

OBJECTIVE: The aim of this study was to evaluate the association of bicuspid aortic valve on contemporary outcomes, including reoperation rates, after one-stage correction for interrupted aortic arch with ventricular septal defect or for aortic coarctation with hypoplastic aortic arch and ventricular septal defect. METHODS: Seventy-four consecutive patients (35 boys, 47% and 39 girls, 53%) with interrupted aortic arch (n = 41, 55%) or aortic coarctation with hypoplastic aortic arch (n = 33, 45%) with ventricular septal defect underwent early one-stage correction. Twenty (27%) patients had bicuspid aortic valve, and the remaining 54 (73%) had a tricuspid aortic valve. The median aortic valve annulus diameter was 6.0 mm (IQR: 2.0). Patients' median age was 7 ± 29 days (range, 2-150); median weight was 3.3 ± 0.7 kg (range, 1.5-6.0), with 21 (28%) patients <3.0 kg. Selective brain perfusion through the innominate artery and selective coronary perfusion through the aortic root during aortic arch reconstruction were used in all patients. Statistical analysis was performed using SPSS version 20.0 software (SPSS Inc., Chicago, IL, USA). RESULTS: The early mortality was 1.3%. One premature neonate died in the hospital with extracorporeal membrane oxygenation after aortic coarctation plus ventricular septal defect repair. There was no further mortality. Median follow-up was 5.7 years (IQR: 10.48). Reinterventions occurred in 36 (49%) patients: balloon angioplasty in 18 (24%) patients, reoperations in 4 (5%) patients, and both in 14 (19%) patients. A total of 86 follow-up procedures were required in these 36 (49%) patients: aortic valve valvulopasty (n = 6, 8%), stent implantation (n = 8, 11%), balloon dilatation (n = 39, 53%), and reoperation (n = 33, 45%). The median time to reinterventions was 9.094 years (SE 0.890). A potential risk factor for reintervention after interrupted aortic arch and aortic coarctation with ventricular septal defect repair was bicuspid aortic valve (p = 0.019, Chi2 (1) = 5.457). In addition, a multivariate Cox analysis with backward selection and significance level <0.015 was applied to all variables that showed significant effects in univariable analyzes. This regression confirmed that bicuspid aortic valve (HR = 0.381, p = .016), and interrupted aortic arch (HR = 0.412, p = 0.043) were predictors of late reintervention. All patients had no obvious neurologic impairment in routine examinations at last follow-up. CONCLUSION: Bicuspid aortic valve was a significant risk factor for valve-related reintervention after one-stage repair for aortic arch obstruction with ventricular septal defect due to later development of stenosis associated with higher late morbidity and mortality. Particularly neonates with bicuspid aortic valve will possibly require reintervention in the future. Regular lifelong cardiac follow-up is recommended.

Long-Term Outcome Up To 40 Years after Single Patch Repair of Complete Atrioventricular Septal Defect in Infancy or Childhood.

OBJECTIVES: Patients with repaired complete atrioventricular septal defect (CAVSD) represent an increasing portion of grown-ups with congenital heart disease. For repair of CAVSD, the single-patch technique has been employed first. This technique requires division of the bridging leaflets, thus, among other issues, long-term function of the atrioventricular valves is of particular concern. METHODS: Between 1978 and 2001, 100 consecutive patients with isolated CAVSD underwent single-patch repair in our institution. Hospital mortality was 11%. Primary endpoints were clinical status, atrioventricular valve function, and freedom from reoperation in long term. Follow-up was obtained contacting the patient and/or caregiver, and the referring cardiologist. RESULTS: Eighty-three patients were eligible for long-term follow-up (21.0 ± 8.7, mean ± standard deviation [21.5; 2.1-40.0, median; min-max] years after surgical repair). Actual long-term mortality was 3.4%. Quality of life (QoL; self- or caregiver-reported in patients with Down syndrome) was excellent or good in 81%, mild congestive heart failure was present in 16%, moderate in 3.6% as estimated by New York Heart Association classification. Echocardiography revealed normal systolic left ventricular function in all cases. Regurgitation of the right atrioventricular valve was mild in 48%, mild-moderate in 3.6%, and moderate in 1.2%. The left atrioventricular valve was mildly stenotic in 15% and mild to moderately stenotic in 2%; regurgitation was mild in 54%, mild to moderate in 13%, and moderate in 15% of patients. Freedom from left atrioventricular-valve-related reoperation was 95.3, 92.7, and 89.3% after 5, 10, and 30 years, respectively. Permanent pacemaker therapy, as an immediate result of CAVSD repair (n = 7) or as a result of late-onset sick sinus syndrome (n = 5), required up to six reoperations in single patients. Freedom from pacemaker-related reoperation was 91.4, 84.4, and 51.5% after 5, 10, and 30 years, respectively. CONCLUSION: Up to 40 years after single-patch repair of CAVSD, clinical status and functional results are promising, particularly, in terms of atrioventricular valve function. Permanent pacemaker therapy results in a life-long need for surgical reinterventions.

Using 3D Physical Modeling to Plan Surgical Corrections of Complex Congenital Heart Defects.

Background Understanding the anatomy and physiology of congenital heart defects is crucial for planning interventions in these patients. Congenital heart procedures often involve complex three-dimensional (3D) reconstructions. Excellent imaging techniques are required to depict all anatomical details. We have used and evaluated fast 3D prototyping technology for reconstruction and planning of corrections of complex congenital heart defects. Materials and Methods 3D physical models were constructed from contrast-enhanced computed tomography (CT) datasets of patients with complex congenital heart defect. Two different commercially available printing technologies were used and their clinical application compared. Results Physical models of three different patients were used for preoperative surgical planning. All models showed good correspondence to patient anatomy. Both printing technologies gave excellent results. Conclusion Physical models could be easily constructed with the use of CT datasets. The printing process could be done efficiently, quite rapidly, and cost effectively. Surgical corrections could be planned based on these models.

Expression of inflammation in myocardial tissue of rabbits: comparison of two miniaturized heart-lung machines.

The majority of cases involving the surgical treatment of congenital heart disease require implementation of cardiopulmonary bypass (CPB). However, neonates and infants are particularly prone to serious complications associated with CPB as a result of capillary leak due to cardiovascular failure. These complications are related to the transfusion of foreign blood, the disproportionately large area of contact between the patient's blood and foreign material, as well as the systemic inflammatory response induced by hemolysis. To attenuate these risks, we developed a novel, highly integrative, miniaturized heart-lung machine (MiniHLM) with a static priming volume of only 102 mL. This prototype was tested in comparison with a conventional heart-lung machine (static priming volume 213 mL) using a rabbit animal model. The animals were anesthetized, sternotomized, and connected to CBP via the aorta and right atrium. The aorta was cross-clamped for 1 h. Blood samples for examination were taken at regular intervals. Biopsies of the right atrial appendage (RAA) were removed directly after initiation and after cessation of CPB. After gradual reduction of perfusion with the HLM, all rabbits were successfully weaned from CPB, and the sternum was closed. Foreign blood was not administered in all cases. After cryopreservation of the RAA tissue, de novo transcription of inflammatory cytokines was measured by means of real-time polymerase chain reaction using the comparative CT method. No significant differences in the expression of the inflammatory parameters of the myocardial tissue samples were found between the study groups.

Uni-ventricular palliation vs. bi-ventricular repair: differential inflammatory response.

BACKGROUND: To examine whether uni-ventricular palliation (UVP) and bi-ventricular repair (BVR) result in a different pattern of systemic inflammatory response to pediatric cardiac surgery with extra-corporeal circulation (ECC). METHODS: In 20 children (median age 39.5 months) undergoing either UVP (n = 12) or BVR (n = 8), plasma levels of the inflammatory cytokines TNF-α, IL-6, IL-10, and IL-12 and of procalcitonin (PCT), were measured before, during and after open cardiac surgery up to postoperative day (POD) 10. RESULTS: Epidemiologic, operative- and outcome variables were similar in both groups but post-operative central venous pressure that was higher in UVP. In the whole cohort, the inflammatory response was characterized by an early important, significant and parallel increase of IL-6 and IL-10 that reached their peak values either at the end of ECC (IL-10) or 4 h postoperatively (IL-6), respectively and by a significant and parallel decrease of TNF-α and IL-12 levels after connection to ECC, followed by a bi-phasic significant increase with a first peak 4 h after ECC and a second at POD 10, respectively. Patients after UVP showed a shift of the cytokine balance with lower IL-6- (p = 0.01) after connection to ECC, lower early post-operative TNF-α - (p = 0.02) and IL-12- (p = 0.04) concentrations and lower TNF-α/IL-10-ratio (p = 0.03) as compared with patients with BVR. Levels of PCT were similar in both groups. CONCLUSIONS: UVP is associated with an anti-inflammatory shift of the inflammatory response to cardiac surgery that might be related to the particular hemodynamic situation of patients with UVP.

Myocardial Expression of Estrogen Receptor-mRNA Is Associated With Lower Markers of Post-operative Organ Damage in Young Patients With Congenital Cardiac Defect.

Background: Estrogen receptors (ERs) relate to cardio-protection in adults, but their role in younger patients is not known. We aimed to assess the myocardial expression of ERα- and ERß- mRNA in young patients with congenital cardiac disease and to analyze their putative protective role. Patients and Methods: Twenty children and young adults (seven females and 13 males) with a median age of 13.8 years (interquartile range: 12.3 years) were enrolled in this prospective study. The myocardial expression of ER-mRNA and genes involved in inflammation, growth, and stress response was assessed by real-time PCR and was correlated to post-operative (po) outcome. Results: ER-mRNA was detected in the myocardium of all patients, independently of gender and age. The expression of ER-mRNA correlated with that of mRNA coding for brain natriuretic peptide and for all cytokines tested. A higher ERα-mRNA expression correlated with lower troponin T concentrations at 24 h po (p = 0.032), higher PaO2/FiO2 ratio at 4 h po (p = 0.059), lower fluid retention at 4 h po (p = 0.048), and lower aspartate aminotransferase (AST) levels at 24 h po (p = 0.047). A higher ERß-mRNA expression was also correlated with lower fluid retention at 24 h po (p = 0.048). Patients in whom the levels of ERα- and ERß-mRNA were >P50 had lower troponin T (p = 0.003, respectively) and lower AST concentrations at 24 h po (p = 0.043, respectively) than the others. Conclusions: The expression of ERα- and ERß-mRNA is present in the myocardium of children and young adults with congenital cardiac defect and is associated with lower markers of po organ damage. This suggests that ERs may provide perioperative organ protection in this population.

Proximal Aortic Dilatation and Pulmonary Valve Replacement in Patients with Repaired Tetralogy of Fallot: Is There a Relationship? A Cardiac Magnetic Resonance Imaging Study.

Aortopathy is a known complication whose incidence is growing within the population of tetralogy of Fallot (TOF) patients. Its pathology and relationship with other comorbidities remain unclear. This study was designed to determine the prevalence and predictors of proximal aortic dilatation after TOF repair. We retrospectively investigated all patients who underwent follow-up cardiac magnetic resonance imaging (CMR; at least 4 years after TOF repair) between March 2004 and December 2019. The dimensions at the ascending aorta (AAo) and sinus of Valsalva (SoV) levels were measured. Aortic dilatation was defined as an internal aortic diameter that was >2 standard deviation of the previously published normal values. We included 77 patients (mean age 28.9 ± 10.5 years, 41.5% female, mean follow-up of 24.5 ± 8.1 years). AAo and SoV were dilated in 19 (24.6%) and 43 (55.8%) patients, respectively. Patients with dilated AAo and SoV were older during the corrective surgery (p < 0.001 and p = 0.004, respectively) and during CMR (p = 0.002 and 0.024, respectively) than patients without AAo and SoV dilatation. Patients of the dilated AAo group were more likely to have prior palliative shunt (p = 0.008), longer shunt duration (p = 0.005), and a higher degree of aortic valve regurgitation (AR) fraction (p < 0.001) and to undergo pulmonary (PVR) and/or aortic valve replacement (p < 0.001 and p = 0.013, respectively). PVR (p = 0.048, odds ratio = 6.413, and 95% CI = 1.013-40.619) and higher AR fraction (p = 0.031, odds ratio = 1.194, and 95% CI = 1.017-1.403) were independent predictors for AAo dilatation. Aortopathy is a common progressive complication that may require reintervention and lifelong follow-up. Our study shows that proximal aortic dilatation may be attributed to factors that increase the volume overload across the proximal aorta, including late corrective surgery and palliative shunt. We also found that PVR and higher AR fraction are independent predictors of AAo dilatation.

A newly developed miniaturized heart-lung machine--expression of inflammation in a small animal model.

Cardiopulmonary bypass may cause severe inflammatory reactions and multiorgan failure, especially in premature and low-weight infants. This is due in part to the large area of contact with extrinsic surfaces and the essential addition of foreign blood. Thus, we developed a new miniaturized heart-lung machine (MiniHLM) with a total static priming volume of 102mL (including arterial and venous lines) and tested it in a small animal model. Seven Chinchilla Bastard rabbits were perfused with the MiniHLM (dynamic priming volume 127mL). Seven animals serving as a control were perfused using Dideco Kids and a Stöckert roller pump (modified dynamic priming volume 149mL). The rabbits were anesthetized and sternotomized, followed by cannulation of the aorta and the right atrium. The aorta was clamped for 1h. Blood for examination of inflammation (TNF-α, IL-1ß, IL-6, IL-8, and IL-10) and blood gas analysis were taken before skin incision, 5min before opening of the aorta, 15min after opening of the aorta, and 4 h after the initiation of cardiopulmonary bypass. The parameters of inflammation were expressed by means of the comparative C(T) method (ΔΔC(T) method). After gradual reduction of perfusion with the HLM, the heart was decannulated, and the sternum was closed. All rabbits were successfully weaned from cardiopulmonary bypass. Blood gas analysis was unremarkable in all cases. Foreign blood was not administered. Although statistical significance was not achieved, there was a reduced expression of inflammatory markers in the MiniHLM group. The newly developed MiniHLM prototype was tested successfully in a small animal model in terms of technical function and expression of inflammation. Upcoming tests with the industrially manufactured MiniHLM may reveal the advantages of the MiniHLM in comparison with the conventional HLM.

The Aachen MiniHLM--a miniaturized heart-lung machine for neonates with an integrated rotary blood pump.

The operation of congenital heart defects in neonates often requires the use of heart-lung machines (HLMs) to provide perfusion and oxygenation. This is prevalently followed by serious complications inter alia caused by hemodilution and extrinsic blood contact surfaces. Thus, one goal of developing a HLM for neonates is the reduction of priming volume and contact surface. The currently available systems offer reasonable priming volumes for oxygenators, reservoirs, etc. However, the necessary tubing system contains the highest volumes within the whole system. This is due to the use of roller pumps; hence, the resulting placement of the complete HLM is between 1 and 2 m away from the operating table due to connective tubing between the components. Therefore, we pursued a novel approach for a miniaturized HLM (MiniHLM) by integrating all major system components in one single device. In particular, the MiniHLM is a HLM with the rotary blood pump centrically integrated into the oxygenator and a heat exchanger integrated into the cardiotomy reservoir which is directly connected to the pump inlet. Thus, tubing is only necessary between the patient and MiniHLM. A total priming volume of 102 mL (including arterial filter and a/v line) could be achieved. To validate the overall concept and the specific design we conducted several in vitro and in vivo test series. All tests confirm the novel concept of the MiniHLM. Its low priming volume and blood contact surface may significantly reduce known complications related to cardiopulmonary bypass in neonates (e.g., inflammatory reaction and capillary leak syndrome).

Right Atrial Myocardial Remodeling in Children With Atrial Septal Defect Involves Inflammation, Growth, Fibrosis, and Apoptosis.

Introduction: Myocardial remodeling due to large atrial septum defect (ASD) is macroscopically characterized by dilation of the right-sided cardiac cavities secondary to volume overload, the cellular mechanisms of which are not yet understood. We postulated that inflammation, fibrosis, and cell death are actors of right atrial remodeling secondary to ASD. Patients and Methods: In 12 children with large ASD (median age: 63 months), expression of genes coding for proteins involved in the response to cell stress and -protection, inflammation, growth and angiogenesis, fibrosis, and apoptosis was assessed by RT-PCR in right atrial myocardial biopsies taken during cardiac surgery. The presence of cytokines in myocardial cells was confirmed by immunohistochemistry and effective apoptosis by TUNEL assay. Results: In all patients investigated, a cellular response to early mechanical stress with the initiation of early protective mechanisms, of inflammation (and its control), -growth, and -angiogenesis, of fibrosis and apoptosis was present. The apoptotic index assessed by TUNEL assay averaged 0.3%. Conclusions: In children with large ASD, macroscopic right atrial remodeling relates to cellular mechanisms involving the expression of numerous genes that either still act to protect cells and tissues but that also harm as they initiate and/or sustain inflammation, fibrosis, and cell death by apoptosis. This may contribute to long term morbidity in patients with ASD.

Fatal outcome after heart surgery in PMM2-CDG due to a rare homozygous gene variant with double effects.

Variants in Phosphomannomutase 2 (PMM2) lead to PMM2-CDG, the most frequent congenital disorder of glycosylation (CDG). We here describe the disease course of a ten-month old patient who presented with the classical PMM2-CDG symptoms as cerebellar hypoplasia, retinitis pigmentosa, seizures, short stature, hepato- and splenomegaly, anaemia, recurrent vomiting and inverted mamillae. A severe form of tetralogy of Fallot was diagnosed and corrective surgery was performed at the age of 10 months. At the end of the cardiopulmonary bypass, a sudden oedematous reaction of the myocardium accompanied by biventricular pump failure was observed immediately after heparin antagonization with protamine sulfate. The patient died seven days after surgery, since myocardial function did not recover on ECMO support. We here describe the first patient carrying the homozygous variant g.18313A > T in the PMM2 gene (NG_009209.1) that either can lead to c.394A > T (p.I132F) or even loss of 100 bp due to exon 5 skipping (c.348_447del; p.G117Rfs*4) which is comparable to a null allele. Proliferation and doubling time of the patient's fibroblasts were affected. In addition, we show that the induction of cellular stress by elevating the cell culture temperature to 40 °C led to a decrease of the patients' PMM2 transcript as well as PMM2 protein levels and subsequently to a significant loss of residual activity. We assume that metabolic stressful processes occurring after cardiac surgery led to the drop of the patient's PMM activity below a life-sustaining niveau which paved the way for the fatal outcome.

A bench-top molding method for the production of cell-laden fibrin micro-fibers with longitudinal topography.

Tissue-engineered constructs have great potential in many intervention strategies. In order for these constructs to function optimally, they should ideally mimic the cellular alignment and orientation found in the tissues to be treated. Here we present a simple and reproducible method for the production of cell-laden pure fibrin micro-fibers with longitudinal topography. The micro-fibers were produced using a molding technique and longitudinal topography was induced by a single initial stretch. Using this method, fibers up to 1 m in length and with diameters of 0.2-3 mm could be produced. The micro-fibers were generated with embedded endothelial cells, smooth muscle cell/fibroblasts or Schwann cells. Polarized light and scanning electron microscopy imaging showed that the initial stretch was sufficient to induce longitudinal topography in the fibrin gel. Cells in the unstretched control micro-fibers elongated randomly in both the floating and encapsulated environments, whereas the cells in the stretched micro-fibers responded to the introduced topography by adopting a similar orientation. Proof of concept bottom-up tissue engineering (TE) constructs are shown, all displaying various anisotropic organization of cells within. This simple, economical, versatile and scalable approach for the production of highly orientated and cell-laden micro-fibers is easily transferrable to any TE laboratory.

The Aachen miniaturized heart-lung machine--first results in a small animal model.

Congenital heart surgery most often incorporates extracorporeal circulation. Due to foreign surface contact and the administration of foreign blood in many children, inflammatory response and hemolysis are important matters of debate. This is particularly an issue in premature and low birth-weight newborns. Taking these considerations into account, the Aachen miniaturized heart-lung machine (MiniHLM) with a total static priming volume of 102 mL (including tubing) was developed and tested in a small animal model. Fourteen female Chinchilla Bastard rabbits were operated on using two different kinds of circuits. In eight animals, a conventional HLM with Dideco Kids oxygenator and Stöckert roller pump (Sorin group, Milan, Italy) was used, and the Aachen MiniHLM was employed in six animals. Outcome parameters were hemolysis and blood gas analysis including lactate. The rabbits were anesthetized, and a standard median sternotomy was performed. The ascending aorta and the right atrium were cannulated. After initiating cardiopulmonary bypass, the aorta was cross-clamped, and cardiac arrest was induced by blood cardioplegia. Blood samples for hemolysis and blood gas analysis were drawn before, during, and after cardiopulmonary bypass. After 1 h aortic clamp time, all animals were weaned from cardiopulmonary bypass. Blood gas analysis revealed adequate oxygenation and perfusion during cardiopulmonary bypass, irrespective of the employed perfusion system. The use of the Aachen MiniHLM resulted in a statistically significant reduced decrease in fibrinogen during cardiopulmonary bypass. A trend revealing a reduced increase in free hemoglobin during bypass in the MiniHLM group could also be observed. This newly developed Aachen MiniHLM with low priming volume, reduced hemolysis, and excellent gas transfer (O(2) and CO(2)) may reduce circuit-induced complications during heart surgery in neonates.

Congenital cystic adenomatoid malformation type 0-a rare cause of neonatal death.

OBJECTIVE: We give the first account of failure of extracorporeal membrane oxygenation therapy secondary to congenital cystic malformation of the lung (CCAM) type 0. DESIGN: Case report. SETTING: Pediatric intensive care unit. PATIENT: A female neonate, appropriate for gestational age, with respiratory failure immediately after delivery. INTERVENTIONS: : Cardiopulmonary support with venoarterial extracorporeal membrane oxygenation. RESULTS: There was no improvement of pulmonary function, and the patient died. CCAM type 0 was diagnosed postmortem. CONCLUSIONS: CCAM type 0 should be considered as a rare differential diagnosis of irreversible lung pathologies leading to failure of extracorporeal membrane oxygenation therapy for neonatal respiratory failure.

Aortopexy offers surgical options for a variety of pathological tracheal conditions in paediatric patients.

OBJECTIVES: Aortopexy is widely used; however, many surgeons still regard it with suspicion. To date, there are only a few large series and minimal long-term data. Against this background, our goal was to report our experience, particularly with regard to the recent expansion of indications and modification of diagnostic routine and surgical strategy. METHODS: Between 1994 and 2012, 53 patients (mean age: 1.1 years; 5 weeks-10.2 years) were operated on. Tracheomalacia after the operation for oesophageal atresia was the main indication for aortopexy (74%), followed by tracheal compression by the innominate artery (17%) and other selected indications (9%). Computed tomography angiography has emerged in recent years as the method of choice for preoperative diagnosis. Median sternotomy has replaced lateral thoracotomy, and intraoperative bronchoscopy has become the standard. RESULTS: In contrast to magnetic resonance imaging, computed tomography angiography resulted in perfect visualization of the condition. Median sternotomy and simultaneous bronchoscopy led to immediate readjustment of the aortopexy sutures in 6 patients. There were no surgical deaths or serious morbidities. The mean follow-up was 4.9 (0.3-14.9) years. Two patients with additional complex diseases died during the follow-up period. In all survivors, symptoms improved markedly or disappeared. However, we observed an increased susceptibility to lower respiratory tract infections over the long-term (32%). CONCLUSIONS: Aortopexy is effective for treating tracheomalacia of different origins and other pathological conditions as well. Preoperative computed tomography angiography offers excellent visualization of the condition. Median sternotomy and intraoperative bronchoscopy provide a combination for reliable operative and long-term results. However, many patients still have an increased susceptibility to lower respiratory tract infections.

The use of moderate hypothermia during cardiac surgery is associated with repression of tumour necrosis factor-alpha via inhibition of activating protein-1: an experimental study.

INTRODUCTION: The use of moderate hypothermia during experimental cardiac surgery is associated with decreased expression of tumour necrosis factor (TNF)-alpha in myocardium and with myocardial protection. In order to identify the cellular mechanisms that lead to that repression, we investigated the effect of hypothermia during cardiac surgery on both main signalling pathways involved in systemic inflammation, namely the nuclear factor-kappaB (NF-kappaB) and activating protein-1 pathways. METHOD: Twelve female pigs were randomly subjected to standardized cardiopulmonary bypass with moderate hypothermia or normothermia (temperature 28 degrees C and 37 degrees C, respectively; six pigs in each group). Myocardial probes were sampled from the right ventricle before, during and 6 hours after bypass. We detected mRNA encoding TNF-alpha by competitive RT-PCR and measured protein levels of TNF-alpha, inducible nitric oxide synthase and cyclo-oxygenase-2 by Western blotting. Finally, we assessed the activation of NF-kappaB and activating protein-1, as well as phosphorylation of p38 mitogen-activated protein kinase by electrophoretic mobility shift assay with super shift and/or Western blot. RESULTS: During and after cardiac surgery, animals subjected to hypothermia exhibited lower expression of TNF-alpha and cyclo-oxygenase-2 but not of inducible nitric oxide synthase. This was associated with lower activation of p38 mitogen-activated protein kinase and of its downstream effector activating protein-1 in hypothermic animals. In contrast, NF-kappaB activity was no different between groups. CONCLUSION: These findings indicate that the repression of TNF-alpha associated with moderate hypothermia during cardiac surgery is associated with inhibition of the mitogen-activated protein kinase p38/activating protein-1 pathway and not with inhibition of NF-kappaB. The use of moderate hypothermia during cardiac surgery may mitigate the perioperative systemic inflammatory response and its complications.

Intramyocardial synthesis of pro- and anti-inflammatory cytokines in infants with congenital cardiac defects.

OBJECTIVES: We sought to test the hypothesis that cytokines would be expressed in the myocardium of infants with congenital cardiac defects and to identify the signaling pathways involved. BACKGROUND: Mechanical stress upregulates pro-inflammatory cytokines in the myocardium. METHODS: Fifteen infants with tetralogy of Fallot (TOF) (n = 7) or with ventricular septal defects (VSDs) (n = 8) were investigated. Concentrations of pro- and anti-inflammatory cytokines and of the inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay and/or Western blotting in the right ventricular myocardium taken during cardiac surgery. Activation of the nuclear factor-kappa-B (NF-kappa-B) and p38 mitogen-activated protein kinase (MAPK) pathways was assessed by electrophoretic mobility shift assay with supershift and/or Western blotting, respectively. RESULTS: The pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, and IL-6 and the anti-inflammatory cytokine IL-10 were detected in the myocardium of all patients. Concentrations of the pro-inflammatory cytokines and also of phosphorylated p38 MAPK were higher in patients with TOF than in those with VSD and correlated with the degree of pressure overload of the right ventricle. Levels of phosphorylated I-kappa-B-alpha, iNOS, and IL-10 were similar in patients with TOF and in those with VSD. CONCLUSIONS: Our results show intramyocardial synthesis of pro-inflammatory cytokines in infants with congenital cardiac defects. This is associated with activation of both the NF-kappa-B and p38 MAPK pathways. The latter could be particularly important for the transduction of mechanical signals in the infant's myocardium. Synthesis of IL-10 indicates an intramyocardial anti-inflammatory potential in this age group.

Does cardiac surgery in newborn infants compromise blood cell reactivity to endotoxin?

INTRODUCTION: Neonatal cardiac surgery is associated with a systemic inflammatory reaction that might compromise the reactivity of blood cells against an inflammatory stimulus. Our prospective study was aimed at testing this hypothesis. METHODS: We investigated 17 newborn infants with transposition of the great arteries undergoing arterial switch operation. Ex vivo production of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), of the regulator of the acute-phase response IL-6, and of the natural anti-inflammatory cytokine IL-10 were measured by enzyme-linked immunosorbent assay in the cell culture supernatant after whole blood stimulation by the endotoxin lipopolysaccharide before, 5 and 10 days after the operation. Results were analyzed with respect to postoperative morbidity. RESULTS: The ex vivo production of TNF-alpha and IL-6 was significantly decreased (P < 0.001 and P < 0.002, respectively), whereas ex vivo production of IL-10 tended to be lower 5 days after the operation in comparison with preoperative values (P < 0.1). Ex vivo production of all cytokines reached preoperative values 10 days after cardiac surgery. Preoperative ex vivo production of IL-6 was inversely correlated with the postoperative oxygenation index 4 hours and 24 hours after the operation (P < 0.02). In contrast, postoperative ex vivo production of cytokines did not correlate with postoperative morbidity. CONCLUSION: Our results show that cardiac surgery in newborn infants is associated with a transient but significant decrease in the ex vivo production of the pro-inflammatory cytokines TNF-alpha and IL-6 together with a less pronounced decrease in IL-10 production. This might indicate a transient postoperative anti-inflammatory shift of the cytokine balance in this age group. Our results suggest that higher preoperative ex vivo production of IL-6 is associated with a higher risk for postoperative pulmonary dysfunction.