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Konrad Brockmeier

Publications and source records attributed to Konrad Brockmeier.

At least 19 recordsLinked to original sources
PubMed2006

Superior vena cava stenting and transvenous pacemaker implantation (stent and pace) after the Mustard operation.

The Mustard operation for transposition of the great arteries is associated with good long-term survival. Typical complications at follow-up include progressive loss of sinus node function requiring permanent pacemaker implantation, and systemic venous pathway obstruction often precluding a transvenous approach to pacing. We report on 7 patients (median age 14.1; range 5-19) with bradyarrhythmia requiring permanent pacemaker implantation with associated stenosis (n = 6) or occlusion (n = 1) of the superior vena cava, in whom stent implantation relieved the obstruction and facilitated subsequent transvenous permanent pacing. In five of them stenting and pacemaker implantation were performed during a single procedure; two patients underwent elective pacemaker implantation 6 weeks later. In one patient the pacemaker had to be explanted due to pacemaker pocket infection. In the others the follow-up has been uneventful, with excellent chronic pacing thresholds and appropriate sensing. Two patients have had their generator replaced electively.We conclude that stenting of the SVC stenosis allows implantation of transvenous pacemaker leads with good intermediate term results in patients with a Mustard operation for transposition of the great arteries.

Adolescent↗
PubMed2006

Skipping of Exon 1 in the KCNQ1 gene causes Jervell and Lange-Nielsen syndrome.

The Jervell and Lange-Nielsen syndrome (JLNS) is a rare autosomal recessive form of the long QT syndrome linked with a profound hearing loss caused by mutations affecting both alleles of either the KCNQ1 or the KCNE1 gene. We carried out a mutant screening of the KCNQ1 and KCNE1 genes in a clinical diagnosed German family with JLNS. Family members were examined by single strand conformation polymorphism analysis and PCR and amplified products were characterized by DNA sequence analysis. We identified a splice donor mutation of exon 1 in the KCNQ1 gene (G477+1A). Analysis of lymphocyte RNA by RT-PCR revealed that two symptomatic patients, homozygous for the mutant allele, exclusively produce KCNQ1 transcripts lacking exon 1 leading to a frameshift that introduced a premature termination codon at exon 4. Mutant subunits, functionally characterized in Xenpous oocytes, were unable to form homomeric channels but strongly reduced IKs (slowly activating delayed rectifier potassium current) in vitro (mutant isoforms 1 and 2 by 62 and 86%, respectively), a fact supposed to lead to severely affected heterozygous individuals. However, individuals heterozygous for the mutant allele exhibit an asymptomatic cardiac phenotype. Thus, the observed dominant-negative effect of mutant subunits in vitro is absent in vivo leaving heterozygous individuals unaffected. These data suggest mechanisms that prevent production of truncated KCNQ1 channel subunits in cardiomyocytes of individuals heterozygous for the mutant allele.

Adolescent↗
PubMed2006

Force measurements of human embryonic stem cell-derived cardiomyocytes in an in vitro transplantation model.

Human embryonic stem cell (hESC)-derived cardiomyocytes have been suggested for cardiac cell replacement therapy. However, there are no data on loaded contractions developed by these cells and the regulation thereof. We developed a novel in vitro transplantation model in which beating cardiomyocytes derived from hESCs (line H1) were isolated and transplanted onto noncontractile, ischemically damaged ventricular slices of murine hearts. After 2-3 days, transplanted cells started to integrate mechanically into the existing matrix, resulting in spontaneous movements of the whole preparation. Preparations showed a length-dependent increase of active tension. In transplanted early beating hESC-derived cardiomyocytes, frequency modulation by field stimulation was limited to a small range around their spontaneous beating rate. Our data demonstrate that this novel in vitro transplantation model is well suited to assess the mechanical properties and functional integration of cells suggested for cardiac replacement strategies.

Animals↗
PubMed2006

Wireless Holter transmission in suspected dysrhythmias.

BACKGROUND: In patients with a history of possible dysrhythmias, documentation of an episode is mandatory before any form of treatment is given. Holter recordings with wireless telemetry offer the possibility of continuously recording electrocardiograms for days or even weeks with instantaneous analysis of the data in the physician's office. METHODS: Thirty-seven patients (20 male; median age, 8.4 years; range, 0.1-22 years), were investigated by using a telemetric Holter system (M120, Schiller, Switzerland), that is, intermittent transmission of the electrocardiographic data to a remote server using cell phone frequencies, with a median duration of the recordings of 6.5 days (range 1-42 days). RESULTS: Recording quality was sufficient in all patients. Problems were related to electrode disconnections only, which were adjusted by contacting the patients. Twenty-eight of 37 recordings showed decisive findings. Of the 28 patients, no treatment was indicated in 16 patients, as subjective symptoms did not correlate with dysrhythmias; psychotherapy was indicated in 2 patients; antiarrhythmic medication was initiated or intensified in 5 patients; radiofrequency ablation was successfully performed in 5 patients; and 1 patient received an ICD. In 6 of 9 patients with negative Holter findings, a loop recorder implantation (Medtronic, Minneapolis, Minn) was indicated. In 1 patient, no dysrhythmias were recorded; however, when invasively investigated, ventricular tachycardia was detected and successfully treated by radiofrequency ablation. In 2 patients, no decision has been made to date. CONCLUSIONS: Wireless Holter recordings are useful in detecting dysrhythmias with rare occurrence, are less expensive and less invasive compared with implantable loop recorders, and offer the patient rather wide geographic ranges with sufficient signal quality.

Adolescent↗
PubMed2006

Ventricular slices of adult mouse hearts--a new multicellular in vitro model for electrophysiological studies.

AIM: We established a preparation of adult murine ventricular slices suitable for electrophysiological recordings as a new in vitro model of adult myocardium with preserved in vivo tissue structure. METHODS: Short axis slices (thickness: 150 microm) of adult murine ventricles were prepared with a microtome. Sharp glass electrodes were used for measurements of action potentials (APs) at stimulation frequencies of 2 Hz and 10 Hz. Field potential (FP) recordings by means of microelectrode arrays (MEAs) were performed to map excitation spread. RESULTS: APs showed the characteristics of adult murine ventricular APs: (i) a stable resting membrane potential, (ii) a fast upstroke and (iii) a fast phase 1 repolarization. Application of the Na+ channel blocker lidocaine (30 microM) led to a decline of upstroke slope, amplitude and conduction speed. The unspecific K+ channel blocker 4-aminopyridine (5 mM) caused a prolongation of APD50. The excitation spread was homogenous throughout the ventricular wall. CONCLUSION: Adult murine ventricular slices are electrophysiologically intact and respond physiologically to cardioactive drugs. Thus, they provide a new multicellular in vitro model of adult cardiac tissue suitable for electrophysiological investigations, which in future could be used to study the functional integration of stem cells transplanted in infarcted hearts in vivo.

Action Potentials↗
PubMed2006

Impulse propagation in late-stage embryonic and neonatal murine ventricular slices.

AIM: To evaluate whether field potential recordings from murine ventricular slice preparations serve as a model to investigate impulse propagation. METHOD: Late-stage embryonic and neonatal murine hearts were sliced by a vibratome. Slices were placed on planar microelectrode arrays (MEAs). Field potentials of spontaneously beating and electrically stimulated contractions were recorded. The maximal negative deflection of the field potentials (dV / dt) was calculated to assess the local activation time, to create activation sequence maps, and to estimate conduction velocity. RESULTS: Mapping of impulse propagation of late-stage embryonic and neonatal murine ventricular slices and estimation of conduction velocities is feasible using the MEA technique showing an impulse propagation reflecting anatomical structures and conduction velocities similar to those obtained with other techniques. CONCLUSION: The combination of viable ventricular slice preparations with the MEA technique offers a versatile and powerful technique to study cardiac impulse propagation.

Action Potentials↗
PubMed2006

Stem cells and their potential relevance to paediatric cardiology.

Basic scientists, as well as cardiologists, are caught by the idea of curing ischaemic heart disease with cardiac progenitor or stem cells. This short review provides an overview of our current knowledge on the potential use of stem cells for cardiac disease. Since, in infants and children, aetiologies and pathomechanisms of critical cardiac disease are fundamentally different from those in adults, we will also address the question as to whether such young patients could be a therapeutic target at all, and in which respect it may be necessary to view treatment with stem cells from a different stance in the developing organism.

Adolescent↗
PubMed2006

Who benefits from intervention in, as opposed to screening of, overweight and obese children?

AIMS: StEP TWO is a school- and family-based intervention consisting of extra lessons, healthy nutrition and physical education for overweight and obese children in primary schools, aimed at reducing body mass index by maintenance or reduction of weight, and improving motor abilities. We analysed differences in changes in anthropometric, cardiovascular and obesity parameters between children who underwent intervention, non-participants in intervention, and controls. METHODS: Anthropometric data and waist circumference were recorded for 1678 children; body mass index and body mass index-standard deviation score were calculated. Blood pressure was measured after 5 minutes at rest. 121 overweight and obese children enrolled at 3 schools involved in programmes of intervention were invited to take part; 40 of them completed the programme from November 2003 to July 2004. Of these overweight children, 74 were invited, but did not take part. As controls, we enrolled 155 overweight and obese children from 4 other schools. RESULTS: After the programme, the children involved in intervention showed a lower increase in the body mass index (0.3 plus or minus 1.3 versus 0.7 plus or minus 1.2 kilograms per metre squared) and an approximately three times higher diminution of the body mass index-standard deviation score in comparison with their controls (-0.15 plus or minus 0.26 versus 0.05 plus or minus 0.27). Systolic blood pressure was significantly lowered by 9.5 plus or minus 19.6 millimetres of mercury in those involved in intervention, but increased in the control group by 0.5 plus or minus 16.5 millimetres of mercury. Among those invited but not participating, the increase of the body mass index (0.5 plus or minus 1.3 kilograms per metre squared) was less, and the reduction of the body mass index-standard deviation score (-0.09 plus or minus 0.31) and systolic blood pressure (-5.3 plus or minus 15.6 millimetres of mercury) was higher than in the control group. Overweight but not obese children seem to benefit from a screening examination alone. CONCLUSIONS: Early preventive measures in schools are necessary and effective for overweight and obese primary school children. The screening itself seems also to have a minor positive effect, especially for overweight children. Sustainability of the observed improvements over a longer period remains to be confirmed.

Blood Pressure↗
PubMed2005

Outcome of muscle and bone development in congenital heart disease.

Muscles and bones of patients with congenital heart disease (CHD) are subject to various potentially deleterious influences during growth. The aim of the present study was to analyse the outcome of bone and muscle parameters in adolescents and young adults with a spectrum of CHD. Bone and muscle parameters of the forearm were examined at two standard sites, 4% and 65%, in 29 adolescents and young adults with CHD, aged 14-24 years, by quantitative computed tomography. For the entire study population, bone and muscle parameters did not deviate significantly from the reference values except for age- and gender-corrected body height (ASDS-height: -0.6+/-1.2, p=0.01). Both age- and gender- and height- and gender-corrected (HSDS) abnormal bone mass (BMC) was found at the distal radius in patients with Fontan repair (ASDS-BMC4%: -1.5+/-0.9, p=0.008; HSDS-BMC4%: -1.2+/-1.0, p=0.05) and in those in NYHA class III (ASDS-BMC4%: -1.3+/-0.4, p=0.001; HSDS-BMC4%: -1.4+/-0.5, p=0.004). There was minimal overlap between Fontan patients (n=6) and NYHA class III (5 Fontan patients were in NYHA class I or II). In conclusion, most patients with CHD show a normal muscle and bone development in proportion to their reduced body height. Further follow-up is required to determine whether patients in a worse clinical status (NYHA III) and those with single ventricle physiology are at increased risk of osteoporosis and fractures.

Adolescent↗
PubMed2005

Experience with an ambulatory 12-lead Holter recording system for evaluation of pediatric dysrhythmias.

BACKGROUND: The 12-lead electrocardiogram demonstrates noninvasively many details concerning cardiac arrhythmias and their mechanism, but only for a limited period. A Holter system can record heart rhythm for a longer period, but shows 2 or 3 leads only. An ambulatory 12-lead Holter recording system combines the advantages of both. We report on our experience with the 12-lead Holter system in children. STUDY POPULATION: Twenty-four patients (age range, 3-22 years) underwent one or more 12-lead Holter recordings. Twelve patients had suspected or documented tachyarrhythmia, and 12 patients had suspected or proven long QT syndrome (LQTS). RESULTS: In the tachyarrhythmia group, 4 patients had supraventricular tachycardia and 7 ventricular tachycardia (VT). In the supraventricular tachycardia, group 1 patient had intra-atrial reentrant tachycardia with a single reentrant circuit, whereas another had multiple P-wave morphologies, suggesting multiple circuits. Two others had evidence for concealed atrioventricular accessory pathways. One patient had isolated supraventricular ectopy. In the VT group, 4 patients had uniform VT, and 3 patients had polymorphic VT. One patient with LQTS had macroscopic T-wave alternans. Two others showed intermittent extreme QT prolongation and T-wave notching during 12-lead Holter recording. THERAPEUTIC IMPLICATIONS: Patients with uniform VT underwent catheter ablation, guided in 2 instances by intracardiac pace mapping and comparison with the 12-lead Holter QRS morphology. All reentrant supraventricular arrhythmias with single P-wave morphology were ablated. One patient with intra-atrial reentrant tachycardia and multiple circuits received an antitachycardia pacemaker. In the LQTS group, the neonate with T-wave alternans received mexiletine in addition to beta-blocker therapy. CONCLUSION: In individual patients, the 12-lead Holter system provides important additional information about the arrhythmia and helps to plan appropriate therapy. Intermittent T-wave morphology changes can be diagnosed using 12-lead Holter recordings in patients with LQTS, allowing dynamic T-wave changes to be monitored. In specific cases, this may help identify patients with LQTS and also influence pharmacological therapy.

Adolescent↗
PubMed2005

The electrocardiogram of human embryonic stem cell-derived cardiomyocytes.

Microelectrode arrays enable to map extracellular field potentials of excitable organs (eg, cardiac tissue) in an electrocardiogram-like manner: They allow to detect (a) rhythmicity, (b) the origin and route of excitation, (c) repolarization, and (d) conduction in heart tissue in short- and long-term experimental approaches. Using it as a screening tool for potential side effects of drugs, we here provide evidence for d-sotalol-induced delayed repolarization in human embryonic stem (hES) cell-derived cardiomyocytes. Thus, the combination of the microelectrode array system with cardiac clusters derived from hES cells heralds a paradigm shift toward improved pharmaceutical drug safety. However, the mixture of various cell types in hES cell cardiac clusters (eg, atrial, immature and mature ventricular cardiomyocytes) indicates the strong need for improved selectivity of cardiac differentiation protocols using hES cells.

Action Potentials↗
PubMed2005

Data from the StEP TWO programme showing the effect on blood pressure and different parameters for obesity in overweight and obese primary school children.

UNLABELLED: Obesity in childhood, which is associated with cardiovascular risk factors such as hypertension, is on the increase. Countermeasures are necessary. In this paper, we present the baseline and final data from the StEP TWO programme, a prospective study to prevent overweight and obesity in primary schools. METHODS: We recorded and calculated, from 1689 children, anthropometric data, including analyses of bioelectric impedance, waist and hip circumferences, body mass index and its standard deviation, and the ratio of waist to hip. Blood pressure was measured after 5 minutes at rest. From the three schools involved in a programme of intervention, 121 children were invited to take part, and 40 (33.1 per cent) completed the programme. The effect was compared with 155 overweight and obese children identified at the 4 control schools. RESULTS: 830 (49.5 per cent) boys and 848 girls (50.5 per cent) took part. Their mean age was 8.2 plus or minus 1.3 years, their height was 1.31 plus or minus 0.09 metres, they weighed 30.0 plus or minus 8.2 kilograms, and their mean index of body mass was 17.1 plus or minus 2.9 kilograms per metre squared. Of the children, 7.3 per cent were obese, 10.4 per cent were overweight, 75.7 per cent had normal weights, and 6.6 per cent were underweight. Resting hypertension was observed in 2.3 per cent of the children. Increased blood pressure was associated with a higher body weight, body mass index, standard deviation score for body mass index, and waist and hip circumferences (each p < 0.001), but not with the ratio of waist to hip. Hypertension at rest was also found in 11.0 per cent of obese children, 4.4 per cent of those who were overweight, 1.2 per cent of those with normal weight, and 1.0 per cent of underweight children (p < 0.001). After the intervention, the increase of the body mass index tended to be lower in those in whom we had intervened (p = 0.069), and in these the decrease of the standard deviation score for body mass index was significantly higher (p = 0.028). Systolic blood pressure was reduced by about 10 millimetres of mercury in those in whom we had intervened (p = 0.002), while there were no changes in the control group. Diastolic blood pressure was lowered by 3 millimetres of mercury, but this was not significant. CONCLUSION: Obese children had the highest values for systolic and diastolic blood pressure. Increased levels of blood pressure are associated with other parameters of obesity, such as the circumference of the waist and hip. Early preventive measurements in childhood are necessary, and appropriate intervention appears to be effective.

Blood Pressure↗
PubMed2005

Establishment and characterization of a mouse embryonic heart slice preparation.

BACKGROUND: In contrast to isolated cells, the anatomic and functional integrity of tissue slices remains preserved. Aim of the study was to establish the slice technique in embryonic mouse hearts in order to perform physiological and pharmacological investigations of wild-type mice and genetically engineered mouse models of heart disease. METHODS: Ventricular slices (thickness: 300 mum) were cut from agar-embedded embryonic mouse hearts (ED 16.5-18.5) with a vibratome. Histology, immunostaining with markers for apoptosis induction, intracellular recordings with sharp electrodes and field potential recordings using microelectrode arrays were performed to assess viability. RESULTS: Slices exhibited normal histology without prominent signs of apoptosis for at least 24 hours. Intracellular recordings revealed the typical electrophysiological fingerprint of ventricular cardiomyocytes. Field potential recordings proved that adrenergic and muscarinic signaling was preserved. CONCLUSION: Functionally intact heart slices can be generated from murine embryos.

Action Potentials↗
PubMed2004

Microelectrode arrays: a new tool to measure embryonic heart activity.

The analysis of the sequential excitation of cardiac tissue is of high relevance, both for clinical pathophysiological purposes, eg, detection of sustained ventricular arrhythmias, as well as for experimental electrophysiology. Clinically, different technical approaches such as single electrode measurements and bipolar mapping electrode catheters have been used. In experimental setups several techniques to record cardiac activity have been proposed. Beside the well-established intracellular current-clamp recordings of action potentials, recent studies have performed extracellularly activation sequence mapping or simultaneous multichannel action potential electrode array measurements. Measurement of extracellularly recorded field potentials (FPs) hereby especially provides detailed information about the origin and spread of excitation in the heart. A similar analytical approach for cardiac FPs advanced the analysis of excitation spread and arrhythmic activity in multicellular preparations like developmental differentiation tissue of mouse embryonic stem cells, multicellular preparations of isolated native embryonic cardiomyocytes or the embryonic heart in toto. The use of substrate-integrated Microelectrode Arrays (MEAs, Multi Channel Systems, Reutlingen, Germany) with 60 electrodes of 10-30 microm diameters on a 100-200 microm grid, coated with porous titanium nitride to minimize the impedance allows recording of FPs at a high signal to noise ratio. The possibility to electrically stimulate the tissue further expands the range of applications and bioassays. It may thus facilitate the evaluation of drug research providing detailed information about the interplay of the complex cardiac network, and might improve the predictability of physiological and pathophysiological conditions or drug effects in embryonic heart tissue.

Action Potentials↗
PubMed2004

Closure of a patent arterial duct in a septuagenarian with atrial fibrillation.

We occluded a large arterial duct in a patient with atrial fibrillation, using an Amplatzer duct occluder, with no residual shunt at the end of the procedure. Follow-up revealed recanalization, which was successfully treated with a 4 mm Amplatzer ASD occluder. It is speculated the reopening of the initially occluded duct was the consequence of anticoagulation needed because of the atrial fibrillation.

Aged↗
PubMed2003

Repolarization analysis in children with the long QT syndrome.

QT duration changes were analysed in 26 children with long QT syndrome (median age 9 years). With 12-lead Holter recordings, we found that macroscopically QT adaptation to heart rate changes was slow and only 3 of 26 patients showed abrupt changes in QT interval duration. These changes in the time domain were always accompanied by changes of STT morphology in the 3 of 26 patients. Application of Bazett's heart rate correction algorithm was inappropriate to show true QT changes in this young patient group due to temporary typical large cycle length variations, where moreover an overcorrection of the heart rate impact resulted in reflection of RR interval changes rather than true QT duration changes.

Adolescent↗