We studied the effect of chronic endothelin A receptor blockade by atrasentan on the pulmonary endothelin-1 system and vascular endothelial growth factor (VEGF) expression in piglets with high pulmonary blood flow. Twenty-five 4-week-old piglets with high pulmonary blood flow were randomized to three groups: sham operated (n = 8), placebo (water) (n = 7), or treatment with atrasentan (2 mg/kg per day) (n = 10). After 3 months, mean pulmonary arterial pressure (PAP) was higher in the placebo group than in the sham group [18 ± 2 mm Hg versus 14 ± 1 mm Hg; P < 0.05 (ANOVA)]. Atrasentan treatment was associated with lower cardiac output, PAP (14 ± 1 mm Hg), and medial wall thickness of pulmonary arteries (diameter: 50-150 μM) compared with placebo [13.6 ± 3.0% versus 18.1 ± 4.2%; P < 0.05 (ANOVA)]. Quantitative real-time polymerase chain reaction for endothelin-1, endothelin B receptor, and endothelin-converting enzyme-1 mRNA in lung tissue did not differ. However, immunostaining as well as mRNA for VEGF were lower in atrasentan-treated animals (relative gene expression: atrasentan versus placebo: 0.8 ± 0.3 versus 1.5 ± 0.3; P = 0.009). Atrasentan treatment effectively reduces medial hypertrophy in piglets with chronic pulmonary hyperperfusion. Chronic endothelin A receptor blockade by atrasentan may interfere with the expression of VEGF.

Fibrillar collagens I and III, nonfibrillar collagen IV, and the glycoproteins fibronectin and laminin, are elements of the myocardial extracellular matrix (ECM). Alterations in the normal concentrations and ratios of these elements may reflect remodeling in response to physiologic stress. In the case of patients' post-heart transplantation (HTx), specific patterns of alteration may herald myocardial dysfunction. Right ventricular biopsies were taken from the same 28 HTx patients before implantation and 1 week, 2 weeks, and 1, 2, and 3 years after HTx. The above-noted five ECM proteins, six matrix metalloproteinases (MMPs) and two of their tissue inhibitors (TIMPs) were detected by immunohistochemistry and scored as cells per square millimeter or semiquantitatively. The total connective tissue fibers were detected by connective tissue stain and morphometry. Variations in these ECM components were followed in the same patient cohort over 3 years. In summary, during the first 2 weeks after HTx, a predominant increase in connective tissue occurred. Increases in MMP-8 and MMP-9 were found. By 3 years after transplantation, there was a decrease of connective tissue fibers and a significant reduction of all ECM components and an increase in MMPs and TIMPs. These findings may reflect a pattern of remodeling specific to the transplanted heart.

It is known that the host responds to an increased concentration of collagenase [or matrix metalloproteinase (MMP)-1] by preferentially expressing mRNA for the tissue inhibitor of metalloproteinase-1 (TIMP-1) in order to overcome tissue destruction due to periodontitis. To further elucidate the relation between MMPs and TIMPs in periodontitis-affected tissues, the expression of mRNA for MMP-1, -3 and -8, and TIMP-1 and -2, in 10 gingival samples from patients and five from healthy individuals was assessed by reverse transcription-polymerase chain reaction. The diseased group showed significantly higher levels of MMP-1, -3, -8 and TIMP-1 mRNA relative to β-actin than the control group (mean ± SE: diseased vs healthy (%): 0.26 ± 0.05 vs 0.018 ± 0.0040 for MMP-1; 0.90 ± 0.16 vs 0.063 ± 0.016 for MMP-3; 0.068 ± 0.017 vs 0.006 ± 0.0010 for MMP-8; 12.66 ± 2.90 vs 2.71 ± 0.54 for TIMP-1; p < 0.01). TIMP-2 did not significantly differ between the two groups (1.79 ± 0.33 vs 1.42 ± 0.53; p > 0.05). The preferential increase in the level of MMP-3 mRNA relative to that of MMP-1 and -8 in inflamed gingiva would be relevant to tissue destruction because MMP-3 is a broad-spectrum MMP and a pivotal activator of latent MMP-1 and -8. Therefore, the overall increase in MMP-1, -3 and -8 mRNA in periodontitis-affected gingiva might account for a concerted action of MMPs during connective tissue destruction in periodontitis.

To prospectively assess the incidence of cardiac dysrhythmias before and after closure of atrial septal defects (ASDs) using the Amplatzer septal occluder (ASO), 24-hour Holter electrocardiogyrams (ECGs) were performed before and 1 year after the procedure in 23 pediatric patients (9 male and 14 female). Patients' ages ranged from 2 to 15 years (mean, 7.1 years). All had an ASD of the secundum type that was completely closed (n = 22) or had a small residual shunt (n = 1). No preexisting dysrhythmia was present in 22 patients; atrioventricular nodal reentrant tachycardia had been diagnosed in 1 patient. During the observation period, no clinical dysrhythmia occurred. Analysis of the Holter ECGs before the intervention showed regular sinus rhythm in 20 patients and sinus rhythm with intermittent atrial rhythm in 3 patients. Atrial premature complexes (APCs) were detected in I patient, and a ventricular couplet was present in I patient. The Holier ECG I year after the intervention showed sinus rhythm in 18 patients and sinus rhythm with intermittent atrial rhythm in 5 patients. APCs were still observed in I patient and seen for the first time in 1 patient; 1 patient and rare ventricular premature complexes. In conclusion, cardiac dysrhythmias on Holter ECG in pediatric patients before and 1 year after transcatheter ASD closure with the ASO device are rare and benign. Regular Holter monitoring seems to be useful in detecting late dysrhythmias.

Postoperative laryngospasm during emergence from anaesthesia represents a potentially life-threatening complication. Even if this is successfully overcome using drug therapy, new, serious problems may develop. We report the case of a 3 1/2 -year-old boy of African descent weighing 15 kg who developed a laryngospasm during emergence from anaesthesia. Because the airway obstruction could not be controlled by deepening the anaesthesia again and administering anti-obstructive drugs, the boy was given 15 mg succinylcholine. Thereafter prolonged apnea developed such that the patient had to be admitted to the pediatric intensive care unit. The child was extubated 6 h later and the further course was normal so that he could be released from the hospital the following day. Further diagnostic study revealed a dibucaine-sensitive, fluoride-resistant pseudocholinesterase in the plasma, which is a rare form of atypical pseudocholinesterase, explaining the prolonged arousal phase after the administration of succinylcholine. Three significant aspects of this case are discussed: 1. risk factors and treatment of perioperative airway obstruction 2. factors and treatment of prolonged apnea, and 3. delayed arousal reactions and their management in an outpatient setting.

BACKGROUND:Patients with transposition of the great arteries who underwent an atrial repair in infancy are likely to develop right ventricular dysfunction later in life. For these patients a two-stage arterial switch operation has been advocated by some groups but mortality even from the initial pulmonary banding procedure for retraining the left ventricle has been reported to be considerable. We asked whether pathological alterations of the left ventricular myocardium could explain for the failure of the left ventricle observed in patients after two-stage arterial switch operations.METHODS:Twelve patients aged 16.9 [8-25.4] years (median [range]) with transposition of the great arteries after atrial repair in infancy were enrolled. Median follow-up interval was 15.8 [7.8-22.1] years. Measurements of right and left ventricular systolic function were performed by echocardiography. In addition all patients underwent cardiac catheterization. Endomyocardial biopsies were taken from the right and left ventricle and examined histopathologically.RESULTS:Two out of twelve patients showed mildly reduced systolic right ventricular function. Systolic function of the left ventricle was normal in all patients on echocardiography but six out of twelve patients showed clusters of fibrous and fatty degeneration on biopsy specimens obtained from the left ventricle.CONCLUSION:We conclude that degenerative left ventricular myocardial changes could serve as an explanation for left ventricular failing when retraining the left ventricle during two-stage arterial switch operations.

Die Fallot-Tetralogie wurde erstmals im Jahre 1571 von Nils Stensen und danach 1671 von Nicolaus Steno, 1777 von Sandifort, 1784 von Hunter und 1866 von Peacock pathologischanatomisch beschrieben H. H. Fallot wies 1888 auf die vier anatomischen Befunde hin, die der Tetralogie zugrunde liegen [18]. Aber erst 1944 konnte den ersten Patienten durch eine Palliativoperation geholfen werden [12].

During the last decade, the understanding of the long QT-syndrome (LQTS) as an inherited arrhythmogenic disease has dramatically increased. The LQTS has been recognized to be a heterogeneous family of ion-channel disorders caused by numerous mutations in at least six distinct gene loci, thus, explaining the prolongation of the myocardial repolarization. Consecutive studies of the LQTS advanced our knowledge of pathophysiology, clinical course and possible therapeutic impact.    As a genetically determined disorder the clinical manifestation of the LQTS naturally starts in childhood. In 34% of the children, syncope or cardiac arrest was found to occur before the age of 15 years. In addition, 54% of all LQTS patients who died from sudden cardiac death were less than 20years old.    Most cases in children are identified by the detection of a prolonged QT interval while evaluating unexplained cases of syncope or by family investigations of an index patient. In children more than in adults, however, normal values of QT interval duration are dependent from age, gender, heart rate and circadian variations. Therefore, the moreover applied correction formulas for the QT interval to heart rate ratio have to be used with caution in the pediatric setting. A useful and reliable tool for the analysis of QT duration, QT patterns, and its circadian variation is multilead digital Holter recordings. The determination of the diagnosis is based on clinical findings according to the criteria of the "International LQTS Registry". Genetic investigations, however, are actually diagnostic in about 50% of the patients, but are not effective as a clinical screening tool.    The genetically determined LQTS types (LQT1-LQT6) differ significantly in terms of reaction to triggering stimuli that may induce life-threatening arrhythmias and their response to treatment. In LQT1, physical stress will more likely induce Torsades de Pointes than in the LQT3, which is more sensitive to emotional stress. The typical LQTS treatment is life-long medication with beta blocking agents; however, in LQT3 patients with mutations in the cardiac sodium channel gene, treatment with mexiletine may have advantages. In order to prevent bradycardia or by short-long sequences inducible torsades, the use of implantable pacemakers is recommended. Stellectomy to minimize cardiac adrenergic susceptibility has proven to be less effective in children. Recently, the rapid technical improvement of implantable defibrillators led to a more frequent use of these devices in children.    In order to sufficiently manage pediatric LQTS patients in the future and to reduce the risk of sudden cardiac death due to inherited arrhythmias, a national and international multicenter approach is necessary.