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Item does not contain fulltext, RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10(-10), OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10(-5)). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus.

Contains fulltext : 249972.pdf (Publisher’s version ) (Open Access), RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10(-10), OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10(-5)). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus.

Contains fulltext : 249972.pdf (Publisher’s version ) (Open Access), RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10(-10), OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10(-5)). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus.

Background: Facing the global COVID-19 pandemic University teaching has been digitalized and German medical faculties took great effort to offer curricular contents online as they agreed that semesters during pandemic should not be suspended. Skill training is an essential part of medical education and cannot be fully digitalized nor should it be omitted. The pandemic demonstrates that skills like ultrasound are essential when treating critical ill patients. Medical faculties use peer assisted learning (PAL) concepts to teach skills, like ultrasound through specially trained student tutors.Aim: Here, we would like to share our experiences and elaborate how ultrasound teaching can be safely performed during the pandemic with an emphasis on adjustment of an existing PAL teaching concept.Method: At the hospital of Saarland University, we implemented a PAL teaching concept for abdominal, including emergency, ultrasound, and echocardiography, called "sonoBYstudents" to teach sonography to undergraduate medical students. Students are generally taught in small groups of 5 people in 90min sessions over a time of 8 weeks with an objective structured clinical exam (OSCE) at the end of the course program. Each semester nearly 50 students are taught in abdominal and emergency ultrasound and 30 students in echocardiography. Over five years, more than 600 students have been taught with at least 30 students being trained as student tutors. Given the pandemic, course size, course interval and total course time and total course time were adapted to the hygienic precautions. Results: 45 and 30 students were taught in abdominal ultrasound and echocardiography respectively achieving their learning goals measured via OSCE at the end of the courses. OSCE results were the same when compared to previous semesters. Conclusion: PAL as a teaching concept lives out of sustained educational strategies like practical and didactical trainings and an ongoing recruitment of new student tutors. Susp, Hintergrund: Die globale COVID-19-Pandemie führte zu einer raschen Digitalisierung der universitären Lehre. Innerhalb der medizinischen Fakultäten Deutschlands herrschte der Konsens, dass während der Pandemie kein Semester ausgesetzt werden soll. Daher wurden mit viel Mühe, weite Teile der Lehrinhalte online angeboten. Das Unterrichten von praktischen Fertigkeiten ist ein wesentlicher Bestandteil der medizinischen Ausbildung und kann nicht digitalisiert, jedoch auch nicht ausgelassen werden. Die Pandemie zeigt, dass praktische Fertigkeiten wie Ultraschall bei der Behandlung kritisch kranker Patienten unerlässlich sind. Die medizinischen Fakultäten in Deutschland nutzen daher Peer-Assisted-Learning (PAL) Konzepte, als modernes Lehrmodel, um solche praktischen Fertigkeiten, wie Ultraschall, durch speziell ausgebildete studentische Tutoren zu vermitteln.Ziel: Wir möchten unsere Erfahrung teilen und aufzeigen, wie der studentische Ultraschallunterricht während der Pandemie sicher durchgeführt werden kann, wobei der Schwerpunkt auf der Anpassung eines bestehenden PAL-Lehrkonzepts liegt.Methode: An der medizinischen Fakultät der Universität des Saarlandes, führten wir vor 5 Jahren ein PAL-Lehrkonzept, genannt "sonoBYstudents", ein um Medizinstudenten in der Abdomen-, einschließlich Notfall-Sonographie und Echokardiographie zu unterrichten. Die Studenten werden in Kleingruppen à 5 Personen in 90-minütigen praktischen Seminaren über einen Zeitraum von 8 Wochen unterrichtet. Der Lernerfolg wird durch eine validierte OSCE (objective structured clinical examination) am Ende des Kursprogramms überprüft. Jedes Semester werden ca. 60 Studenten in der Abdomen- und Notfall-Sonographie und 30 Studenten in der Echokardiographie unterrichtet. In fünf Jahren konnten mehr als 600 Studenten unterrichtet sowie mehr als 30 Studenten als studentische Tutoren ausgebildet. Aktuell wurden angesichts der Pandemie Kursgröße, Kursintervall und Gesamtkurszeit, entsprechend einem Hygienekonzept, an

Eine pathologische Druckerhöhung im pulmonalen Gefäßsystem (pulmonale Hypertonie, PH) wurde bisher definiert durch einen invasiv gemessenen mittleren pulmonalarteriellen Druck (mPAP) ≥25 mm Hg in Ruhe. Auf dem 6th World Symposium on Pulmonary Hypertension (WSPH) in Nizza 2018 wurde eine neue Definition der PH vorgeschlagen, die die Senkung der Obergrenze des normalen mPAP von 24 auf 20 mm Hg beinhaltet. Obwohl keine Evidenz aus pädiatrischen Studien hierfür vorliegt, wurde diese neue PH-Definition (mPAP >20 mm Hg) aus Gründen der Einheitlichkeit auch von der pädiatrischen „Task Force“ des WSPH 2018 übernommen. Die vorliegende Stellungnahme der Arbeitsgemeinschaft Pulmonale Hypertonie (AGPH) der Deutschen Gesellschaft für Pädiatrische Kardiologie und angeborene Herzfehler e. V. (DGPK) erläutert die zugrunde liegende Rationale und mögliche Konsequenzen dieser Definitionsänderung. Insbesondere stellt sie klar, dass diese Änderung der Definition aktuell keinen Einfluss auf die Verschreibung von Medikamenten zur gezielten spezifischen Therapie der pulmonalarteriellen Hypertonie hat.

1 januari 2011, Item does not contain fulltext, Transposition of the great arteries (TGA) is a rare disease representing not more than 3-5% of all congenital heart diseases. TGA is a cardiac anomaly in which the aorta arises entirely or largely from the morphological right ventricle and the pulmonary artery from the morphological left ventricle. This is called a ventriculo-arterial discordant connection and when accompanied by an atrio-ventricular concordant connection it is called a complete or D-transposition (D-TGA). The terms congenitally corrected TGA (ccTGA) or L-TGA describe an atrio-ventricular discordant connection. In D-TGA survival can only be achieved if additional shunting is simultaneously present, which possibly has to be created post-natal by the so-called Rashkind maneuver.Nowadays, an early anatomic correction using the arterial switch operation is the treatment of choice. Up to the 1980s, an atrial switch operation according to Senning/Mustard was performed. Apart from echocardiography the imaging modality of choice is usually MRI to assess the complex postoperative anatomy, viability of the myocardium and to perform a volumetric and functional assessment, including MR flow measurements. Multidetector computed tomography (MDCT) is used if there are contraindications to MRI or if an assessment of cardiac and especially coronary anatomy is the main interest.

01 januari 2011, Item does not contain fulltext, Transposition of the great arteries (TGA) is a rare disease representing not more than 3-5% of all congenital heart diseases. TGA is a cardiac anomaly in which the aorta arises entirely or largely from the morphological right ventricle and the pulmonary artery from the morphological left ventricle. This is called a ventriculo-arterial discordant connection and when accompanied by an atrio-ventricular concordant connection it is called a complete or D-transposition (D-TGA). The terms congenitally corrected TGA (ccTGA) or L-TGA describe an atrio-ventricular discordant connection. In D-TGA survival can only be achieved if additional shunting is simultaneously present, which possibly has to be created post-natal by the so-called Rashkind maneuver.Nowadays, an early anatomic correction using the arterial switch operation is the treatment of choice. Up to the 1980s, an atrial switch operation according to Senning/Mustard was performed. Apart from echocardiography the imaging modality of choice is usually MRI to assess the complex postoperative anatomy, viability of the myocardium and to perform a volumetric and functional assessment, including MR flow measurements. Multidetector computed tomography (MDCT) is used if there are contraindications to MRI or if an assessment of cardiac and especially coronary anatomy is the main interest.

01 januari 2011, Item does not contain fulltext, Transposition of the great arteries (TGA) is a rare disease representing not more than 3-5% of all congenital heart diseases. TGA is a cardiac anomaly in which the aorta arises entirely or largely from the morphological right ventricle and the pulmonary artery from the morphological left ventricle. This is called a ventriculo-arterial discordant connection and when accompanied by an atrio-ventricular concordant connection it is called a complete or D-transposition (D-TGA). The terms congenitally corrected TGA (ccTGA) or L-TGA describe an atrio-ventricular discordant connection. In D-TGA survival can only be achieved if additional shunting is simultaneously present, which possibly has to be created post-natal by the so-called Rashkind maneuver.Nowadays, an early anatomic correction using the arterial switch operation is the treatment of choice. Up to the 1980s, an atrial switch operation according to Senning/Mustard was performed. Apart from echocardiography the imaging modality of choice is usually MRI to assess the complex postoperative anatomy, viability of the myocardium and to perform a volumetric and functional assessment, including MR flow measurements. Multidetector computed tomography (MDCT) is used if there are contraindications to MRI or if an assessment of cardiac and especially coronary anatomy is the main interest.

BACKGROUND: Cardiac resynchronisation therapy (CRT) is increasingly used in children in a variety of anatomical and pathophysiological conditions, but published data are scarce. OBJECTIVE: To record current practice and results of CRT in paediatric and congenital heart disease. DESIGN: Retrospective multicentre European survey. SETTING: Paediatric cardiology and cardiac surgery centres. PATIENTS: One hundred and nine patients aged 0.24-73.8 (median 16.9) years with structural congenital heart disease (n = 87), congenital atrioventricular block (n = 12) and dilated cardiomyopathy (n = 10) with systemic left (n = 69), right (n = 36) or single (n = 4) ventricular dysfunction and ventricular dyssynchrony during sinus rhythm (n = 25) or associated with pacing (n = 84). INTERVENTIONS: CRT for a median period of 7.5 months (concurrent cardiac surgery in 16/109). MAIN OUTCOME MEASURES: Functional improvement and echocardiographic change in systemic ventricular function. RESULTS: The z score of the systemic ventricular end-diastolic dimension decreased by median 1.1 (p<0.001). Ejection fraction (EF) or fractional area of change increased by a mean (SD) of 11.5 (14.3)% (p<0.001) and New York Heart Association (NYHA) class improved by median 1.0 grade (p<0.001). Non-response to CRT (18.5%) was multivariably predicted by the presence of primary dilated cardiomyopathy (p = 0.002) and poor NYHA class (p = 0.003). Presence of a systemic left ventricle was the strongest multivariable predictor of improvement in EF/fractional area of change (p<0.001). Results were independent of the number of patients treated in each contributing centre. CONCLUSION: Heart failure associated with ventricular pacing is the largest indication for CRT in paediatric and congenital heart disease. CRT efficacy varies widely with the underlying anatomical and pathophysiological substrate.

Ziel: Ermittlung von rechts- und linksventrikulären Herzparametern sowie von Zeitparametern, welche die größte Beziehung zum Auftreten von ventrikulären Arrhythmien bei Patienten nach chirurgisch korrigierter Fallotscher Tetralogie haben. Methoden: 67 Patienten, davon 22 weiblich und 45 männlich, mit einem mittleren Alter von 20 a (Spanne von 3,5 bis 54 a) wurden in einem MRT Gyroscan ACS-NT (Philips, Best, The Netherlands) untersucht. Das mittlere Alter zum Zeitpunkt der Korrekturoperation war 6,8 a (mit einer Spanne von 1 Monat bis 40 a). Bei 39 Patienten wurde als Operationsmethode ein transannulärer oder subvalvulärer Patch gewählt, bei 28 Patienten die Anlage eines Conduits. Bei 31 Patienten erfolgten eine oder zwei Reoperationen. Die Volumetrie der Ventrikel erfolgte mit einer SSFP-Sequenz in Multislice-Multiphasen-Technik entweder in Atemstop oder mit Hilfe der Navigatortechnik. Es wurden links- und rechtsventrikuläre Volumina, Ejektionsfraktionen (RV-EF und LV-EF) und Muskelmassen erhoben. Zur Ermittlung der pulmonalen Regurgitationsfraktion (RF) wurde eine MR-Flußmessung in Phasenkontrast-Technik im Pulmonalarterienhauptstamm senkrecht zum Gefäßverlauf durchgeführt. Alle erhobenen Daten wurden sowohl in einer univariaten Regressionsanalyse zueinander, als auch in einer multiplen Regressionsanalyse zur Dauer des QRS-Komplexes in Beziehung gesetzt. Ergebnisse: 58 Patienten hatten einen RSB. Die mittlere Dauer des QRS-Komplexes betrug 132 ms (+/- 29 ms). Die Flußmessung wurde bei 58 Patienten durchgeführt und zeigte 42 milde bis moderate sowie 12 schwere Pulmonalinsuffizienzen. In der univariaten Regressionsanalyse fand sich eine Korrelation zwischen RF und QRS-Dauer (r=0,49; p, Objective - to evaluate those right and left ventricular parameters which have the greatest effect on genesis of cardiac arrhythmias in patients after surgical repair of tetralogy of fallot (TOF). Methods - 67 patients, 22 female and 45 male, with a mean age of 20.0 years (range 3 ½ to 54 years) were studied using a Gyroscan ACS-NT (Philips, Best, The Netherlands). Mean age at surgical repair was 6,8 years (range 1 month to 40 years). Valveless repair with a transannular or subvalvular patch was performed in 39 patients whereas in 28 patients a conduit was used. 31 patients underwent two or three surgical interventions. Measurements of the ventricles were performed with a multislice multiphase gradient echo sequence either with a breathhold technique or with respiratory gating. We obtained left and right ventricular volumes, ejection fractions (EF) and myocardial masses. To quantify the regurgitation fraction (RF) of the pulmonary insuffiency (PI) we performed a velocity encoded gradient echo measurement in the main pulmonary artery in a transverse section. Acquired data was evaluated in an univariate logistic regression analysis on all factors assessed and in a multi variate data analysis with backward selection. Results - 58 patients had a right bundle branch block. Mean QRS duration was 132 ms (+/-29 ms). Flow velocity mapping could be performed in 58 patients and showed 42 mild to moderate and 12 severe cases of PI. In the univariate analysis a significant correlation was found between RF and QRS duration (r=0,49; p

Ziel: Ermittlung von rechts- und linksventrikulären Herzparametern sowie von Zeitparametern, welche die größte Beziehung zum Auftreten von ventrikulären Arrhythmien bei Patienten nach chirurgisch korrigierter Fallotscher Tetralogie haben. Methoden: 67 Patienten, davon 22 weiblich und 45 männlich, mit einem mittleren Alter von 20 a (Spanne von 3,5 bis 54 a) wurden in einem MRT Gyroscan ACS-NT (Philips, Best, The Netherlands) untersucht. Das mittlere Alter zum Zeitpunkt der Korrekturoperation war 6,8 a (mit einer Spanne von 1 Monat bis 40 a). Bei 39 Patienten wurde als Operationsmethode ein transannulärer oder subvalvulärer Patch gewählt, bei 28 Patienten die Anlage eines Conduits. Bei 31 Patienten erfolgten eine oder zwei Reoperationen. Die Volumetrie der Ventrikel erfolgte mit einer SSFP-Sequenz in Multislice-Multiphasen-Technik entweder in Atemstop oder mit Hilfe der Navigatortechnik. Es wurden links- und rechtsventrikuläre Volumina, Ejektionsfraktionen (RV-EF und LV-EF) und Muskelmassen erhoben. Zur Ermittlung der pulmonalen Regurgitationsfraktion (RF) wurde eine MR-Flußmessung in Phasenkontrast-Technik im Pulmonalarterienhauptstamm senkrecht zum Gefäßverlauf durchgeführt. Alle erhobenen Daten wurden sowohl in einer univariaten Regressionsanalyse zueinander, als auch in einer multiplen Regressionsanalyse zur Dauer des QRS-Komplexes in Beziehung gesetzt. Ergebnisse: 58 Patienten hatten einen RSB. Die mittlere Dauer des QRS-Komplexes betrug 132 ms (+/- 29 ms). Die Flußmessung wurde bei 58 Patienten durchgeführt und zeigte 42 milde bis moderate sowie 12 schwere Pulmonalinsuffizienzen. In der univariaten Regressionsanalyse fand sich eine Korrelation zwischen RF und QRS-Dauer (r=0,49; p, Objective - to evaluate those right and left ventricular parameters which have the greatest effect on genesis of cardiac arrhythmias in patients after surgical repair of tetralogy of fallot (TOF). Methods - 67 patients, 22 female and 45 male, with a mean age of 20.0 years (range 3 ½ to 54 years) were studied using a Gyroscan ACS-NT (Philips, Best, The Netherlands). Mean age at surgical repair was 6,8 years (range 1 month to 40 years). Valveless repair with a transannular or subvalvular patch was performed in 39 patients whereas in 28 patients a conduit was used. 31 patients underwent two or three surgical interventions. Measurements of the ventricles were performed with a multislice multiphase gradient echo sequence either with a breathhold technique or with respiratory gating. We obtained left and right ventricular volumes, ejection fractions (EF) and myocardial masses. To quantify the regurgitation fraction (RF) of the pulmonary insuffiency (PI) we performed a velocity encoded gradient echo measurement in the main pulmonary artery in a transverse section. Acquired data was evaluated in an univariate logistic regression analysis on all factors assessed and in a multi variate data analysis with backward selection. Results - 58 patients had a right bundle branch block. Mean QRS duration was 132 ms (+/-29 ms). Flow velocity mapping could be performed in 58 patients and showed 42 mild to moderate and 12 severe cases of PI. In the univariate analysis a significant correlation was found between RF and QRS duration (r=0,49; p

Kreislaufstillstand in tiefer Hypothermie (KSTH) wird in der Herzchirurgie zur Korrektur komplexer angeborener Herzfehler angewendet. In den letzten Jahren zeigte sich eine Abnahme der Morbidität und Mortalität nach kardiochirurgischen Eingriffen. Es entstanden aber gleichzeitig Bedenken über eine Beeinträchtigung der neurologischen Funktion und psychomotorischen Entwicklung der operierten Kinder. Wir untersuchten das morphologische Schädigungsmuster im Gehirn nach extrakorporaler Zirkulation mit Kreislaufstillstand in tiefer Hypothermie (KSTH) in einem neonatalen Tiermodell. Zusätzlich evaluierten wir morphologisch den Einfluss einer neuroprotektiven Vorbehandlung mit systemischer und intrathekaler Applikation von Methylprednisolon (MP). Material und Methoden: 24 neugeborenen Ferkeln mit einem Alter unter 1 Woche (Gewicht: 2,1 ± 0,5 kg KG) wurden mittels eines cardiopulmonalen Bypass(CPB) bei 15 °C rektaler Körpertemperatur einem totalen Kreislaufstillstand (KSTH) von 120 Minuten ausgesetzt. Nach Reperfusion wurden die Tiere vom CPB entwöhnt und für 6 Std. überwacht. Eine Gruppe ohne Intervention mit 12 Tieren diente als Kontrollgruppe, bei 7 Tieren wurde eine systemische und bei 5 Tieren eine intrathekale Methylprednisolongabe (Urbason) präoperativ durchgeführt. Das Gehirn wurde nach Fixierung regional histologisch und immunhistochemisch untersucht. Die nekrotischen und apoptotischen Neurone wurden quantitativ in Hippocampus, Kortex, Stammganglien und Kleinhirn erfasst. Molekulargenetische Untersuchungen erfolgten im frontalen Kortex und es wurde die Genexpression mittels "Real-time PCR" für das Hitze-Schock-Protein 70 kD (HSP 70) und die apoptotischen Gene Bak, FAS und Bcl-xL erfasst. Ergebnisse: Das Schädigungsmuster nach KSTH von 120 Minuten bestand aus Nekrose der Neuronen mit einem Fokus in Hippocampus, Kleinhirn und Kortex. Zusätzlich kam es im Gyrus dentatus zum Auftreten apoptotischer Neuronenveränderungen, wobei durch die MP-Vorbehandlung die Anzahl apopt, We evaluated the mode of neuronal cell injury and the possible neuroprotective effect of pretreatment with high dose steroids in a neonatal piglet model with CPB and 120 minutes deep hypothermic circulatory arrest (DHCA). Methods: 24 neonatal piglets (age < 10 days and 2,1 ± 0,5 kg BW) were included in this study. Three groups were formed, one group without any additional pharmacological treatment (n=12) served as control group, two groups with a high dose methylprednisolone (MP) pretreatment, where 30 mg / kg/ BW MP (Urbason) was administered either systemically preoperatively (n=7), or intrathecally 4-6 hours preoperatively (n=5). All animals were anaesthetized, intubated and mechanically ventilated. After median sternotomy the animals were connected to CPB by cannulation of the aorta and right atrium. Full flow CPB (200 ml/kg/min) was initiated to achieve homogeneous systemic cooling. Circulatory arrest for 120 min. was induced when rectal temperature of 15°C was achieved. After rewarmed reperfusion and establishment of stable cardiac ejection the animals were weaned from CPB and monitored for 6-8 hours. Thereafter the animals were sacrificed and the brain was immediately removed, cut in standardized sections and fixated and frozen for further histological and immunohistochemical studies. Neuronal cells were counted in cerebral cortex, basal ganglia, hippocampal region and cerebellum in respect to apoptotic and hypoxic-necrotic neuronal cell changes in each animal. Real-time PCR was performed from frozen brain sections for analysis of expression of heat-shock-protein 70kD (HSP 70), FAS, Bak and Bcl-xl. Results: The main preliminary findings of this neonatal ischemic brain model were the quantitative evaluation of cell injury including perivascular astroglial cells and necrotic and apoptotic neuronal cell changes. The systemic application of high dose methylprednisolone lead only to a slight reduction of edema, but it produced a significant hyperglycemia and aggra

Kreislaufstillstand in tiefer Hypothermie (KSTH) wird in der Herzchirurgie zur Korrektur komplexer angeborener Herzfehler angewendet. In den letzten Jahren zeigte sich eine Abnahme der Morbidität und Mortalität nach kardiochirurgischen Eingriffen. Es entstanden aber gleichzeitig Bedenken über eine Beeinträchtigung der neurologischen Funktion und psychomotorischen Entwicklung der operierten Kinder. Wir untersuchten das morphologische Schädigungsmuster im Gehirn nach extrakorporaler Zirkulation mit Kreislaufstillstand in tiefer Hypothermie (KSTH) in einem neonatalen Tiermodell. Zusätzlich evaluierten wir morphologisch den Einfluss einer neuroprotektiven Vorbehandlung mit systemischer und intrathekaler Applikation von Methylprednisolon (MP). Material und Methoden: 24 neugeborenen Ferkeln mit einem Alter unter 1 Woche (Gewicht: 2,1 ± 0,5 kg KG) wurden mittels eines cardiopulmonalen Bypass(CPB) bei 15 °C rektaler Körpertemperatur einem totalen Kreislaufstillstand (KSTH) von 120 Minuten ausgesetzt. Nach Reperfusion wurden die Tiere vom CPB entwöhnt und für 6 Std. überwacht. Eine Gruppe ohne Intervention mit 12 Tieren diente als Kontrollgruppe, bei 7 Tieren wurde eine systemische und bei 5 Tieren eine intrathekale Methylprednisolongabe (Urbason) präoperativ durchgeführt. Das Gehirn wurde nach Fixierung regional histologisch und immunhistochemisch untersucht. Die nekrotischen und apoptotischen Neurone wurden quantitativ in Hippocampus, Kortex, Stammganglien und Kleinhirn erfasst. Molekulargenetische Untersuchungen erfolgten im frontalen Kortex und es wurde die Genexpression mittels "Real-time PCR" für das Hitze-Schock-Protein 70 kD (HSP 70) und die apoptotischen Gene Bak, FAS und Bcl-xL erfasst. Ergebnisse: Das Schädigungsmuster nach KSTH von 120 Minuten bestand aus Nekrose der Neuronen mit einem Fokus in Hippocampus, Kleinhirn und Kortex. Zusätzlich kam es im Gyrus dentatus zum Auftreten apoptotischer Neuronenveränderungen, wobei durch die MP-Vorbehandlung die Anzahl apopt, We evaluated the mode of neuronal cell injury and the possible neuroprotective effect of pretreatment with high dose steroids in a neonatal piglet model with CPB and 120 minutes deep hypothermic circulatory arrest (DHCA). Methods: 24 neonatal piglets (age < 10 days and 2,1 ± 0,5 kg BW) were included in this study. Three groups were formed, one group without any additional pharmacological treatment (n=12) served as control group, two groups with a high dose methylprednisolone (MP) pretreatment, where 30 mg / kg/ BW MP (Urbason) was administered either systemically preoperatively (n=7), or intrathecally 4-6 hours preoperatively (n=5). All animals were anaesthetized, intubated and mechanically ventilated. After median sternotomy the animals were connected to CPB by cannulation of the aorta and right atrium. Full flow CPB (200 ml/kg/min) was initiated to achieve homogeneous systemic cooling. Circulatory arrest for 120 min. was induced when rectal temperature of 15°C was achieved. After rewarmed reperfusion and establishment of stable cardiac ejection the animals were weaned from CPB and monitored for 6-8 hours. Thereafter the animals were sacrificed and the brain was immediately removed, cut in standardized sections and fixated and frozen for further histological and immunohistochemical studies. Neuronal cells were counted in cerebral cortex, basal ganglia, hippocampal region and cerebellum in respect to apoptotic and hypoxic-necrotic neuronal cell changes in each animal. Real-time PCR was performed from frozen brain sections for analysis of expression of heat-shock-protein 70kD (HSP 70), FAS, Bak and Bcl-xl. Results: The main preliminary findings of this neonatal ischemic brain model were the quantitative evaluation of cell injury including perivascular astroglial cells and necrotic and apoptotic neuronal cell changes. The systemic application of high dose methylprednisolone lead only to a slight reduction of edema, but it produced a significant hyperglycemia and aggra