T Budde

Publications of T Budde

• Thalamic afferent activation of supragranular layers in auditory cortex in vitro: a voltage sensitive dye study.

  Authors: T. Broicher, H-J Bidmon, B Kamuf, P. Coulon, A Gorji, H C Pape, E J Speckmann, T Budde

  Neuroscience. 10/2009;

  We studied auditory thalamocortical interactions in vitro, using an auditory thalamocortical brain slice preparation. Cortical activity evoked by electrical stimulation of the medial geniculateWe studied auditory thalamocortical interactions in vitro, using an auditory thalamocortical brain slice preparation. Cortical activity evoked by electrical stimulation of the medial geniculate nucleus (MGN) was investigated through field potential recordings and voltage sensitive dyes. Experiments were performed in slices obtained from adult mice (9-14 weeks). Stimulus evoked activity was detected in the granular and supragranular layers after a short latency (5-6 ms). In 9-14 weeks old mice infragranular activity was detected in 10 of 24 preparations and was found to be increased in younger mice (p 31-64). In 14 of 24 slices a prominent horizontal spread was observed, which extended into cortical areas lateral to A1. In these experiments, the shortest onset latencies and largest signal amplitudes were located in the supragranular layers of A1. In areas lateral to A1, shortest onset latencies were located in the granular layer, while largest signal amplitudes were found in the supragranular layers. Evoked cortical activity was sensitive to removal of extracellular Ca(2+) or application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 muM). Short repetitive stimulation, resembling thalamic burst activity (three pulses at 100 Hz), resulted in an increase of signal amplitude and excited area by approximately 25%, without changing the overall spatiotemporal activity profile. Blockade of N-methyl-d-aspartate receptors by 2-amino-5-phosphonopentanoate (AP5, 50 muM) reduced amplitudes and excited area by approximately 15-30%, irrespective of stimulation frequency. Application of bicuculline (10 muM) greatly increased cortical responses to thalamic stimulation. Under these conditions, evoked activity displayed a pronounced horizontal spread in combination with a 2-3-fold increase in amplitude. In conclusion, afferent thalamic inputs primarily activate supragranular and granular layers in the auditory cortex of adult mice. This activation is predominantly mediated by non-NMDA receptors, while GABA(A) receptor-mediated inhibition limits the horizontal and vertical spread of activity.

• [Multiple sclerosis - a channelopathy? : Targeting ion channels and transporters in inflammatory neurodegeneration.]

  Authors: S G Meuth, N Melzer, C Kleinschnitz, T Budde, H Wiendl

  Der Nervenarzt. 12/2008;

  Multiple sclerosis (MS) has traditionally been regarded as an inflammatory demyelinating disorder of the CNS in which clinical symptoms result from axon conduction block caused by myelin degradation.Multiple sclerosis (MS) has traditionally been regarded as an inflammatory demyelinating disorder of the CNS in which clinical symptoms result from axon conduction block caused by myelin degradation. However, typical accumulation of permanent neurological deficits during the clinical course of MS cannot be explained solely by de- and remyelinating processes. It is considered to be rather due to neuronal degeneration, for which several reasons could be identified depending on the state of the disease. First, neurons and their axons can be damaged by infiltrating lymphocytes and macrophages either directly by cell-to-cell contact or by the release of harmful mediators such as nitric oxide or glutamate. Second, indirect injury to neurons and axons may occur through the loss of trophic support by neighbouring oligodendrocytes due to destruction of both the myelin sheath and the oligodendrocyte itself. Third, redistribution of certain voltage- and ligand-gated ion channels and transporters along naked demyelinated axons restores axonal conduction but also leads to excessive spatially restricted electrical activity of the axonal membrane, intracellular calcium accumulation, impairment of mitochondrial function, and subsequent neuronal degeneration. The neuroprotective potential of pharmacological modulation of these channels and transporters using already approved drugs has been demonstrated in several animal studies, is the subject of current clinical trials and will be the topic of this review.

• Ca2+-induced Ca2+ release supports the relay mode of activity in thalamocortical cells.

  Authors: T Budde, F Sieg, K H Braunewell, E D Gundelfinger, H C Pape

  Neuron. 06/2000; 26(2):483-92.

  Ca2+ ions play an important role during rhythmic bursting of thalamocortical neurons within sleep. The function of Ca2+ during the tonic relay mode of these neurons during wakefulness is less clear.Ca2+ ions play an important role during rhythmic bursting of thalamocortical neurons within sleep. The function of Ca2+ during the tonic relay mode of these neurons during wakefulness is less clear. Here, we report that tonic activity in thalamocortical cells results in an increase in the intracellular Ca2+ concentration and subsequent release of Ca2+ from intracellular stores mediated via ryanodine receptors (RyRs). Blockade of Ca2+ release shifted the regular firing of single action potentials toward the generation of spike clusters. Regular spike firing and intracellular Ca2+ release thus appear to be functionally coupled in a positive feedback manner, thereby supporting the relay mode of thalamocortical cells during wakefulness. Regulatory influences may be coupled to this system via the cyclic ADP ribose pathway.

• A prognostic computer model to individually predict post-procedural complications in interventional cardiology: the INTERVENT Project.

  Authors: T Budde, M Haude, H W Höpp, S Kerber, G Caspari, G Fassbender, M Fingerhut, I Novopashenny, Y Ogurol, G Breithardt, R Erbel, E Erdmann, M B Wischnewsky

  European heart journal. 03/1999; 20(5):354-63.

  AIMS: The purpose of this part of the INTERVENT project was (1) to redefine and individually predict post-procedural complications associated with coronary interventions, includingAIMS: The purpose of this part of the INTERVENT project was (1) to redefine and individually predict post-procedural complications associated with coronary interventions, including alternative/adjunctive techniques to PTCA and (2) to employ the prognostic INTERVENT computer model to clarify the structural relationship between (pre)-procedural risk factors and post-procedural outcome. METHODS AND RESULTS: In a multicentre study, 2500 data items of 455 consecutive patients (mean age: 61.1+/-8.3 years: 33-84 years) undergoing coronary interventions at three university centres were analysed. 80.4% of the patients were male, 16.7% had unstable angina, and 5.1%/10.1% acute/subacute myocardial infarction. There were multiple or multivessel stenoses in 16.0%, vessel bending >90 degrees in 14.5%, irregular vessel contours in 65.0%, moderate calcifications in 20.9%, moderate/severe vessel tortuosity in 53.2% and a diameter stenosis of 90%-99% in 44.4% of cases. The in-lab (out-of-lab) complications were: 0.4% (0.9%) death, 1.8% (0.2%) abrupt vessel closure with myocardial infarction and 5.5% (4.0) haemodynamic disorders. CONCLUSION: Computer algorithms derived from artificial intelligence were able to predict the individual risk of these post-procedural complications with an accuracy of >95% and to explain the structural relationship between risk factors and post-procedural complications. The most important prognostic factors were: heart failure (NYHA class), use of adjunctive/alternative techniques (rotablation, atherectomy, laser), acute coronary ischaemia, pre-existent cardiac medication, stenosis length, stenosis morphology (calcification), gender, age, amount of contrast agent and smoker status. Pre-medication with aspirin or other cardiac medication had a beneficial effect. Techniques, such as laser angioplasty or atherectomy were predictors for post-procedural complications. Single predictors alone were not able to describe the individual outcome completely.

• The voltage-dependent conductances of rat neocortical layer I neurons.

  Authors: T Budde, J A White

  The European journal of neuroscience. 08/1998; 10(7):2309-21.

  Whole cell patch-clamp techniques were used to study voltage-dependent sodium (Na+), calcium (Ca2+), and potassium (K+) conductances in acutely isolated neurons from cortical layer I of adult rats.Whole cell patch-clamp techniques were used to study voltage-dependent sodium (Na+), calcium (Ca2+), and potassium (K+) conductances in acutely isolated neurons from cortical layer I of adult rats. Layer I cells were identified by means of gamma-aminobutyric acid (GABA) immunocytochemistry. Positive stainings for the Ca2+-binding protein calretinin in a subset of cells, indicated the presence of Cajal-Retzius (C-R) cells. All investigated cells displayed a rather homogeneous profile of voltage-dependent membrane currents. A fast Na+ current activated at about -45 mV, was half-maximal steady-state inactivated at -66.6 mV, and recovery from inactivation followed a two-exponential process (tau1 = 8.4 ms and tau2 = 858.8 ms). Na+ currents declined rapidly with two voltage-dependent time constants, reaching baseline current after some tens of milliseconds. In a subset of cells (< 50%) a constant current level of < 65 pA remained at the end of a 90 ms step. A transient outward current (Ifast) activated approximately -40 mV, declined rapidly with a voltage-insensitive time constant (tau approximately 350 ms) and was relatively insensitive to tetraethylammonium (TEA, 20 mM). Ifast was separated into two components based on their sensitivity to 4-aminopyridine (4-AP): one was blocked by low concentrations (40 microM) and a second by high concentrations (6 mM). After elimination of Ifast by a conditioning prepulse (50 ms to -50 mV), a slow K+ current (I(KV)) could be studied in isolation. I(KV) was only moderately affected by 4-AP (6 mM), while TEA (20 mM) blocked most (> 80%) of the current. I(KV) activated at about -40 mV, declined monoexponentially in a voltage-dependent manner (tau approximately 850 ms at -30 mV), and revealed an incomplete steady-state inactivation. In addition to Ifast and I(KV), indications of a Ca2+-dependent outward current component were found. When Na+ currents, Ifast, and I(KV) were blocked by tetrodotoxin (TTX, 1 microM), 4-AP (6 mM) and TEA (20 mM) an inward current carried by Ca2+ was found. Ca2+ currents activated at depolarized potentials at about -30 mV, were completely blocked by 50 microM cadmium (Cd2+), were sensitive to verapamil (approximately 40% block by 10 microM), and were not affected by nickel (50 microM). During current clamp recordings, isolated layer I neurons displayed fast spiking behaviour with short action potentials (approximately 2 ms, measured at half maximal amplitude) of relative small amplitude (approximately 83 mV, measured from the action potential threshold).

• Distribution of L-type calcium channels in rat thalamic neurones.

  Authors: T Budde, T Munsch, H C Pape

  The European journal of neuroscience. 03/1998; 10(2):586-97.

  One major pathway for calcium entry into neurones is through voltage-activated calcium channels. The distribution of calcium channels over the membrane surface is important for their contribution toOne major pathway for calcium entry into neurones is through voltage-activated calcium channels. The distribution of calcium channels over the membrane surface is important for their contribution to neuronal function. Electrophysiological recordings from thalamic cells in situ and after acute isolation demonstrated the presence of high-voltage activated calcium currents. The use of specific L-type calcium channel agonists and antagonists of the dihydropyridine type revealed an about 40% contribution of L-type channels to the total high-voltage-activated calcium current. In order to localize L-type calcium channels in thalamic neurones, fluorescent dihydropyridines were used. They were combined with the fluorescent dye RH414, which allowed the use of a ratio technique and thereby the determination of channel density. The distribution of L-type channels was analysed in the three main thalamic cell types: thalamocortical relay cells, local interneurones and reticular thalamic neurones. While channel density was highest in the soma and decreased significantly in the dendritic region, channels appeared to be clustered differentially in the three types of cells. In thalamocortical cells, L-type channels were clustered in high density around the base of dendrites, while they were more evenly distributed on the soma of interneurones. Reticular thalamic neurones exhibited high density of L-type channels in more central somatic regions. The differential localization of L-type calcium channels found in this study implies their predominate involvement in the regulation of somatic and proximal dendritic calcium-dependent processes, which may be of importance for specific thalamic functions, such as those mediating the transition from rhythmic burst activity during sleep to single spike activity during wakefulness or regulating the relay of visual information.

• A prognostic computer model to predict individual outcome in interventional cardiology. The INTERVENT Project.

  Authors: T Budde, M Haude, H W Höpp, S Kerber, G Caspari, G Fassbender, M Fingerhut, I Novopashenny, G Breithardt, R Erbel, E Erdmann, M B Wischnewsky

  European heart journal. 10/1997; 18(10):1611-9.

  It is not yet possible to predict an individual's outcome from percutaneous transluminal coronary angioplasty or alternative/adjunctive coronary interventional techniques. The purpose of theIt is not yet possible to predict an individual's outcome from percutaneous transluminal coronary angioplasty or alternative/adjunctive coronary interventional techniques. The purpose of the INTERVENT project is to redefine complications associated with coronary interventions, to set up a prognostic computer model to predict individual outcome and to compare the results to those of conventional statistical techniques. 2500 data items were analysed in 455 consecutive patients (mean age: 61.1 +/- 8.3 years; range 33-84 years; 80.4% male, 16.7% unstable angina, 5.1%/10.1% acute/subacute myocardial infarction) undergoing coronary interventions at three university centres. In-lab/out-of-lab complication rates were 0.4%/0.9% (death), 1.8%/0.2% (abrupt vessel closure with myocardial infarction) and 5.5%/4.0% (haemodynamic complications). Computer algorithms derived by applying techniques from artificial intelligence were able (1) to reduce the set of possible relevant risk factors from 2500 to about 40, (2) to predict individual risk with an accuracy of > 95% and (3) to explain the structural relationship between outcome and risk factors. Patient data from two centres were used to construct and test the algorithm. Data from a third centre were used to evaluate the algorithm. The most important predictors-were acute myocardial infarction, heart failure (NYHA class > II), unstable angina, complex lesions, high low density lipoprotein cholesterol and duration of coronary heart disease. Neither age nor gender impaired the percutaneous transluminal coronary angioplasty results in acute ischaemic syndromes; however, for stable angina, procedural risk increased with age. There was little risk from primary percutaneous transluminal coronary angioplasty in acute myocardial infarction in patients with NYHA heart failure classes I-II; however, the risk was high for patients in NYHA classes > II, either with or without additional thrombolysis. Alternative/adjunctive intervention techniques were no predictors for in-lab-, but were predictors for post-procedural complications.

• Lack of regulation by intracellular Ca2+ of the hyperpolarization-activated cation current in rat thalamic neurones.

  Authors: T Budde, G Biella, T Munsch, H C Pape

  The Journal of physiology. 09/1997; 503 ( Pt 1):79-85.

  1. The regulation of the hyperpolarization-activated cation current, Ih, in thalamocortical neurones by intracellular calcium ions has been implemented in a number of mathematical models on the1. The regulation of the hyperpolarization-activated cation current, Ih, in thalamocortical neurones by intracellular calcium ions has been implemented in a number of mathematical models on the waxing and waning behaviour of synchronized rhythmic activity in thalamocortical circuits. In the present study, the Ca2+ dependence of Ih in thalamocortical neurones was experimentally investigated by combining Ca2+ imaging and patch-clamp techniques in the ventrobasal thalamic complex (VB) in vitro. 2. Properties of Ih were analysed before and during rhythmic stimulation of Ca2+ entry by trains of depolarizing voltage pulses. Despite a significant increase in intracellular Ca2+ concentration ([Ca2+]i) from resting levels of 74 +/- 23 nM to 251 +/- 78 nM upon rhythmic stimulation, significant differences in the voltage dependence of Ih activation did not occur (half-maximal activation at -86.4 +/- 1.3 mV vs. -85.2 +/- 2.9 mV; slope of the activation curve, 11.2 +/- 2.4 mV vs. 12.5 +/- 2.5 mV). Recording of Ih with predefined values of [Ca2+]i (13.2 nM or 10.01 microM in the patch pipette) revealed no significant differences in the activation curve or the fully activated I-V relationship of Ih. 3. In comparison, stimulation of the intracellular cyclic adenosine monophosphate (cAMP) pathway induced a significantly positive shift in Ih voltage dependence of +5.1 +/- 1.9 mV, with no alteration in the fully activated I-V relationship. 4. These data argue against a direct regulation of Ih by intracellular Ca2+, and particularly do not support a primary role of Ca(2+)-dependent modulation of the Ih channels in the waxing and waning of sleep spindle oscillations in thalamocortical neurones.

• Voltage-activated intracellular calcium transients in thalamic relay cells and interneurons.

  Authors: T Munsch, T Budde, H C Pape

  Neuroreport. 08/1997; 8(11):2411-8.

  The dynamics of intracellular calcium concentration ([Ca2+]i) following activation of low voltage-activated (LVA) and high voltage-activated (HVA) Ca2+ currents were studied in identified relayThe dynamics of intracellular calcium concentration ([Ca2+]i) following activation of low voltage-activated (LVA) and high voltage-activated (HVA) Ca2+ currents were studied in identified relay neurons and interneurons of the rat dorsal lateral geniculate nucleus (LGNd) in situ using Ca2+ imaging and patch-clamp techniques. In relay neurons, [Ca2+]i transients associated with the LVA Ca2+ current showed a fairly homogeneous somatodendritic distribution, whereas HVA transients significantly decreased to 65% of the somatic value at 60 microns dendritic distance. In interneurons, LVA transients significantly increased to 239% of the somatic value at 60 microns dendritic distance, whereas HVA transients were not significantly different in the soma and dendrites. These results indicate differences in [Ca2+]i dynamics, which may reflect a heterogeneous distribution of Ca2+ channels contributing to subcellular compartmentation in the two types of thalamic neurons.

• Biphasic defibrillation using a single capacitor with large capacitance: reduction of peak voltages and ICD device size.

  Authors: M Block, D Hammel, D Böcker, M Borggrefe, T Budde, F Isbruch, H H Scheld, G Breithardt

  Pacing and clinical electrophysiology : PACE. 03/1996; 19(2):207-14.

  The volume of current implantable cardioverter defibrillators (ICD) is not convenient for pectoral implantation. One way to reduce the size of the pulse generator is to find a more effectiveThe volume of current implantable cardioverter defibrillators (ICD) is not convenient for pectoral implantation. One way to reduce the size of the pulse generator is to find a more effective defibrillation pulse waveform generated from smaller volume capacitors. In a prospective randomized crossover study we compared the step-down defibrillation threshold (DFT) of a standard biphasic waveform (STD), delivered by two 250-microF capacitors connected in series with an 80% tilt, to an experimental biphasic waveform delivered by a single 450-microF capacitor with a 60% tilt. The experimental waveform delivered the same energy with a lower peak voltage and a longer duration (LVLD). Intraoperatively, in 25 patients receiving endocardial (n = 12) or endocardial-subcutaneous array (n = 13) defibrillation leads, the DFT was determined for both waveforms. Energy requirements did not differ at DFT for the STD and LVLD waveforms with the low impedance (32 +/- 4 omega) endocardial-subcutaneous array defibrillation lead system (6.4 +/- 4.4 J and 5.9 +/- 4.2 J, respectively) or increased slightly (P = 0.06) with the higher impedance (42 +/- 4 omega) endocardial lead system (10.4 +/- 4.6 J and 12.7 +/- 5.7 J, respectively). However, the voltage needed at DFT was one-third lower with the LVLD waveform than with the STD waveform for both lead systems (256 +/- 85 V vs 154 +/- 51 V and 348 +/- 76 V vs 232 +/- 54 V, respectively). Thus, a single capacitor with a large capacitance can generate a defibrillation pulse with a substantial lower peak voltage requirement without significantly increasing the energy requirements. The volume reduction in using a single capacitor can decrease ICD device size.

• Bipolar transvenous defibrillation: efficacy of two different positions of the anode.

  Authors: M Block, D Hammel, D Böcker, M Borggrefe, T Budde, M Castrucci, C Fastenrath, H H Scheld, G Breithardt

  Pacing and clinical electrophysiology : PACE. 12/1995; 18(11):1995-2000.

  For most nonthoracotomy defibrillation lead systems, the transvenous anode can positioned independently of the right ventricular (RV) cathode. Usually a vertical position in the superior vena cavaFor most nonthoracotomy defibrillation lead systems, the transvenous anode can positioned independently of the right ventricular (RV) cathode. Usually a vertical position in the superior vena cava (SVC) is chosen. However, it is unknown if this position yields the optimal defibrillation threshold (DFT). Therefore, in 15 patients undergoing defibrillator implantation the SVC position was compared in a crossover study design with a horizontal position in the left brachiocephalic vein (BCV). Mean DFT was not different for SVC and BCV (19.2 +/- 9.6 J vs 18.5 +/- 9.1 J) but DFT of individual patients differed by up to 12 joules. A positive correlation between impedance and DFT in the BCV position (r = 0.6; P < or = 0.05) indicated that the improved geometry of the defibrillation field with the BCV position is opposed by a higher impedance found for this position (63 +/- 15 omega vs 52 +/- 7 omega). Thus, defibrillation is not improved in general although individual patients might benefit.

• Angiographic, intravascular ultrasound and functional findings early after orthotopic heart transplantation.

  Authors: S Kerber, A Rahmel, O Heinemann-Vechtel, T Budde, M Deng, H H Scheld, G Breithardt

  International journal of cardiology. 05/1995; 49(2):119-29.

  Accelerated graft atherosclerosis is responsible for increased mortality and morbidity among heart transplant recipients. The aim of this in-vivo study was to evaluate coronary atherosclerotic vesselAccelerated graft atherosclerosis is responsible for increased mortality and morbidity among heart transplant recipients. The aim of this in-vivo study was to evaluate coronary atherosclerotic vessel alterations and endothelial function. Seventeen patients (14 males; mean age 49.3 years; range 24 to 69) were studied an average of 11 weeks (range 5 to 21) after heart transplantation because of coronary artery disease (n = 8), dilative cardiomyopathy (n = 7), mitral valve replacement (n = 1) and left atrial metastases of a leiomyosarcoma (n = 1). Mean age of the donor hearts (9 males) was 29 years (range 12 to 55). All recipients underwent biplane ventriculography and coronary angiography. In this study population, a total of 120 coronary segments (main stem, 21; left anterior descending artery, 85; circumflex artery, 14) were analyzed by intravascular ultrasound (20 MHz, 3.5F). In 13 patients, acetylcholine was infused into the proximal left anterior descending artery (10(-8) to 10(-5) M) to evaluate vasomotion within this segment. Regional contraction abnormalities were documented in 2 patients. Nine segments angiographically showed non-critical stenoses (5 patients). Intravascular ultrasound detected 52 cross-sectional areas with a three-layer pattern indicating intimal thickening. Mean circumferential extension of intimal proliferation was 192 degrees, mean intimal thickness 0.35 mm. Only 5 segments of the sonographically pathological cross-sectional areas showed angiographical evidence of atherosclerotic lesions. Intracoronary administration of acetylcholine at doses of 10(-8) and 10(-7) M resulted in vasoconstriction of the examined coronary segment in only 2 patients; the intracoronary application of acetylcholine at doses of 10(-6) and 10(-5) M revealed coronary vasoconstriction in 10 of the total of 13 patients. Using intravascular ultrasound, coronary artery lesions in heart transplant recipients can already be depicted at a very early stage. The abnormal response to acetylcholine in most of the heart recipients is independent of the extent of atherosclerotic vessel abnormalities documented by ultrasound or angiography.

• Intracoronary stenting after unsuccessful PTCA. Early restenosis and explanation of stents during bypass surgery.

  Authors: A Enbergs, C Fechtrup, S Kerber, T Budde, A W Geiger, H H Scheld, G Breithardt

  International journal of cardiology. 03/1995; 48(2):109-13.

  The case of a 63-year-old man is described, who received two intracoronary Palmaz-Schatz-Stents after dissection and occlusion following PTCA of two segments of the left anterior descending branch ofThe case of a 63-year-old man is described, who received two intracoronary Palmaz-Schatz-Stents after dissection and occlusion following PTCA of two segments of the left anterior descending branch of the left coronary artery. Because of recurrent angina caused by early restenosis in the 'unprotected' segment between the stents, surgical revascularisation was performed and the stents were removed.

• Clinical significance and management of ventricular arrhythmias in heart failure.

  Authors: H Kottkamp, T Budde, B Lamp, W Haverkamp, M Borggrefe, G Breithardt

  European heart journal. 01/1995; 15 Suppl D:155-63.

  Ventricular arrhythmias are a frequent finding in patients with heart failure, and heart failure is a major underlying condition which is correlated to sudden death. Therefore, both sudden death andVentricular arrhythmias are a frequent finding in patients with heart failure, and heart failure is a major underlying condition which is correlated to sudden death. Therefore, both sudden death and death from progression of heart failure strongly overlap. Besides long-term ECG recording, newer diagnostic techniques have been developed. The prognostic significance of the signal-averaged ECG in patients with advanced left ventricular dysfunction in the presence of coronary artery disease has been demonstrated; however, in patients with dilated cardiomyopathy, signal-averaging for detection of late potentials has not yet been clearly established as a useful diagnostic tool. Furthermore, heart period variability has been shown to correlate to overall mortality but not to a specific mechanism. Finally, programmed ventricular stimulation, though useful in patients with left ventricular dysfunction and/or heart failure in the setting of coronary artery disease, is of questionable significance in patients with dilated cardiomyopathy. With increasing degrees of left ventricular dysfunction, the efficacy of antiarrhythmic drugs decreases. On the other hand, with increasing degrees of heart failure, antiarrhythmic drugs demonstrate a greater negative inotropic effect, more frequent proarrhythmic effects, and more frequent bradyarrhythmias. Currently, several ongoing amiodarone trials are assessing different approaches of antiarrhythmic treatment in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

• Plasma Lp(a) levels correlate with number, severity, and length-extension of coronary lesions in male patients undergoing coronary arteriography for clinically suspected coronary atherosclerosis.

  Authors: T Budde, C Fechtrup, E Bösenberg, C Vielhauer, A Enbergs, H Schulte, G Assmann, G Breithardt

  Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association. 12/1994; 14(11):1730-6.

  The relation between lipoprotein(a) [Lp(a)] as an independent risk factor for coronary atherosclerosis and the severity and extension of angiographically detectable coronary atherosclerotic lesionsThe relation between lipoprotein(a) [Lp(a)] as an independent risk factor for coronary atherosclerosis and the severity and extension of angiographically detectable coronary atherosclerotic lesions has not been systematically evaluated. In 118 male patients (54.3 +/- 7.4 years) with suspected coronary artery disease and without a history of myocardial infarction undergoing coronary angiography, the relation between plasma Lp(a) levels and other lipoproteins and the severity and extension of coronary lesions was studied. The coronary angiograms were evaluated in a blinded manner according to three scores: vessel score (0 to 3 points for 0 to 3 vessels with stenoses > or = 70%), stenosis score (0 to 32 points; number and severity of coronary stenoses or lesions), and extent score (0 to 100 points; length-extension of all coronary lesions in relation to the total coronary vessel length). The score values obtained were analyzed for correlations with age and levels of total cholesterol (6.08 +/- 1.26 mmol/L; mean +/- SD), high-density lipoprotein cholesterol (1.04 +/- 0.33 mmol/L), low-density lipoprotein cholesterol (4.18 +/- 1.15 mmol/L), triglycerides (1.88 +/- 1.37 mmol/L), and Lp(a) in plasma (19.5 +/- 22.6 mg/dL). Bivariate correlation analysis resulted in positive correlations between Lp(a) and vessel score (P < .01), stenosis score (P < .01), and extent score (P < .05). With multivariate analyses, besides Lp(a) plasma level (nl), only patient age showed a significant correlation to all three scores used, whereas none of the lipid parameters correlated significantly with all three scores.

• [Significance of intravascular ultrasound in arteriosclerotic calcified intima plaques: in vitro comparison of 20 and 12.5 MHz transducers]

  Authors: T M Link, S Kerber, C Fechtrup, M Pöppelmann, T Kleinen, S Blasius, T Budde, G Breithardt, P E Peters

  RöFo : Fortschritte auf dem Gebiete der Röntgenstrahlen und der Nuklearmedizin. 12/1994; 161(6):540-6.

  The aim of this in vitro study was to analyze the diagnostic performance of intravascular ultrasound (IVUS) in vessel wall calcifications and to compare the accuracy of mechanical 12.5 and 20 MHzThe aim of this in vitro study was to analyze the diagnostic performance of intravascular ultrasound (IVUS) in vessel wall calcifications and to compare the accuracy of mechanical 12.5 and 20 MHz transducers. Fourty-three sections of 10 vessels with signs of arteriosclerotic disease on pathologic examination were examined. Slices 500 microns thick were obtained and examined radiographically at 9 fold magnification. In each section, identical segments were defined, amounting to a total of 344 segments. The IVUS sections were analyzed by 3 experienced readers. For statistical evaluation ROC analysis was performed using magnification radiography as a reference. An area under the curve (AUC) of 0.79 was obtained for the 12.5 transducer and of 0.83 for the 20 MHz transducer. Additionally, sensitivity, specificity, and accuracy were determined. Sensitivity depended on the morphology, size, and density of the calcified lesions. We therefore conclude that the sensitivity of intravascular ultrasound concerning calcified arteriosclerotic plaques is limited and that there is no significant (p < 0.01) difference between mechanical 20 and 12.5 MHz transducers in examining iliac arteries.

• Transvenous-subcutaneous defibrillation leads: effect of transvenous electrode polarity on defibrillation threshold.

  Authors: M Block, D Hammel, D Böcker, M Borggrefe, T Budde, F Isbruch, H H Scheld, G Breithardt

  Journal of cardiovascular electrophysiology. 11/1994; 5(11):912-8.

  INTRODUCTION: The defibrillation threshold (DFT) of a transvenous-subcutaneous electrode configuration is sometimes unacceptably high. To obtain a DFT with a sufficient safety margin, theINTRODUCTION: The defibrillation threshold (DFT) of a transvenous-subcutaneous electrode configuration is sometimes unacceptably high. To obtain a DFT with a sufficient safety margin, the defibrillation field can be modified by repositioning the electrodes or more easily by a change of electrode polarity. In a prospective randomized cross-over study, the effect of transvenous electrode polarity on DFT was evaluated. METHODS AND RESULTS: In 21 patients receiving transvenous-subcutaneous defibrillation leads, the DFT was determined intraoperatively for two electrode configurations. Two monophasic defibrillation pulses were delivered in sequential mode between either the right ventricular (RV) electrode as common cathode and the superior vena cava (SVC) and subcutaneous electrodes as anodes (configuration I) or the SVC electrode as common cathode and the RV and subcutaneous electrodes as anodes (configuration II). In each patient, both electrode configurations were used alternately with declining energies (25, 15, 10, 5, 2 J) until failure of defibrillation occurred. The DFT did not differ between both configurations (18.3 +/- 8.2 J vs 18.9 +/- 8.9 J; P = 0.72). Eleven patients had the same DFT with both electrode configurations, 5 patients a lower DFT with the RV electrode as cathode, and 5 patients a lower DFT with the SVC as cathode. Four patients had a sufficiently low DFT (< or = 25 J) with only 1 of the 2 configurations. CONCLUSION: A change of electrode polarity of transvenous-subcutaneous defibrillation electrodes may result in effective defibrillation if the first electrode polarity tested fails to defibrillate. In general, neither the RV electrode nor the SVC electrode is superior if used as a common cathode in combination with a subcutaneous anodal chest patch.

• Prevention of Ca(2+)-mediated action potentials in GABAergic local circuit neurones of rat thalamus by a transient K+ current.

  Authors: H C Pape, T Budde, R Mager, Z F Kisvárday

  The Journal of physiology. 09/1994; 478 Pt 3:403-22.

  1. Neurones enzymatically dissociated from the rat dorsal lateral geniculate nucleus (LGN) were identified as GABAergic local circuit interneurones and geniculocortical relay cells, based upon1. Neurones enzymatically dissociated from the rat dorsal lateral geniculate nucleus (LGN) were identified as GABAergic local circuit interneurones and geniculocortical relay cells, based upon quantitative analysis of soma profiles, immunohistochemical detection of GABA or glutamic acid decarboxylase, and basic electrogenic behaviour. 2. During whole-cell current-clamp recording, isolated LGN neurones generated firing patterns resembling those in intact tissue, with the most striking difference relating to the presence in relay cells of a Ca2+ action potential with a low threshold of activation, capable of triggering fast spikes, and the absence of a regenerative Ca2+ response with a low threshold of activation in local circuit cells. 3. Whole-cell voltage-clamp experiments demonstrated that both classes of LGN neurones possess at least two voltage-dependent membrane currents which operate in a range of membrane potentials negative to the threshold for generation of Na(+)-K(+)-mediated spikes: the T-type Ca2+ current (IT) and an A-type K+ current (IA). Taking into account the differences in membrane surface area, the average size of IT was similar in the two types of neurones, and interneurones possessed a slightly larger A-conductance. 4. In local circuit neurones, the ranges of steady-state inactivation and activation of IT and IA were largely overlapping (VH = 81.1 vs. -82.8 mV), both currents activated at around -70 mV, and they rapidly increased in amplitude with further depolarization. In relay cells, the inactivation curve of IT was negatively shifted along the voltage axis by about 20 mV compared with that of IA (Vh = -86.1 vs. -69.2 mV), and the activation threshold for IT (at -80 mV) was 20 mV more negative than that for IA. In interneurones, the activation range of IT was shifted to values more positive than that in relay cells (Vh = -54.9 vs. -64.5 mV), whereas the activation range of IA was more negative (Vh = -25.2 vs. -14.5 mV). 5. Under whole-cell voltage-clamp conditions that allowed the combined activation of Ca2+ and K+ currents, depolarizing voltage steps from -110 mV evoked inward currents resembling IT in relay cells and small outward currents indicative of IA in local circuit neurones. After blockade of IA with 4-aminopyridine (4-AP), the same pulse protocol produced IT in both types of neurones. Under current clamp, 4-AP unmasked a regenerative membrane depolarization with a low threshold of activation capable of triggering fast spikes in local circuit neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

• A prospective randomized cross-over comparison of mono- and biphasic defibrillation using nonthoracotomy lead configurations in humans.

  Authors: M Block, D Hammel, D Böcker, M Borggrefe, T Budde, F Isbruch, D Wietholt, H H Scheld, G Breithardt

  Journal of cardiovascular electrophysiology. 08/1994; 5(7):581-90.

  INTRODUCTION: For current implantable defibrillators, the nonthoracotomy approach to implantation fails in a substantial number of patients. In a prospective randomized cross-over study theINTRODUCTION: For current implantable defibrillators, the nonthoracotomy approach to implantation fails in a substantial number of patients. In a prospective randomized cross-over study the defibrillation efficacy of a standard monophasic and a new biphasic waveform was compared for different lead configurations. METHODS AND RESULTS: Intraoperatively, in 79 patients receiving nonthoracotomy defibrillation leads, the defibrillation threshold was determined in the initial lead configuration for the mono- and biphasic waveform. In each patient, both waveforms were used alternately with declining energies (20, 15, 10, 5 J) until failure of defibrillation occurred. Three different initial lead configurations were tested in different, consecutive, nonrandomized patients using a bipolar endocardial defibrillation lead alone (A; n = 36) or in combination with a subcutaneous defibrillation patch (B; n = 24) or array (C; n = 19) lead. The lowest successful defibrillation energy with the biphasic waveform was less than, equal to, or higher than with the monophasic waveform in 64%, 28%, and 8% of patients, respectively, and on average significantly lower with the biphasic waveform for all three lead configurations (A: 11.3 +/- 4.4 J vs 14.5 +/- 4.5 J; B: 9.7 +/- 4.7 J vs 15.1 +/- 4.5 J; C: 7.9 +/- 4.5 J vs 12.4 +/- 4.9 J). Defibrillation efficacy at 20 J was significantly improved by the biphasic waveform (91% vs 76%). CONCLUSION: In combination with nonthoracotomy defibrillation leads, the biphasic waveform of a new implantable cardioverter defibrillator showed superior defibrillation efficacy in comparison to the standard monophasic waveform. Defibrillation thresholds were improved for lead systems with and without a subcutaneous patch or array lead.

• [Allograft vasculopathy in the early phase of orthotopic heart transplantation: angiography, intravascular ultrasound and functional in vivo findings]

  Authors: S Kerber, A Rahmel, U Karbenn, O Heinemann-Vechtel, C Fechtrup, B Lamp, M Block, T Budde, A Hoffmeier, M Weyand

  Zeitschrift für Kardiologie. 04/1994; 83(3):215-24.

  Accelerated graft coronary atherosclerosis disease is the main reason for long-term mortality and morbidity of heart transplant recipients. The aim of this in vivo study was to evaluate coronaryAccelerated graft coronary atherosclerosis disease is the main reason for long-term mortality and morbidity of heart transplant recipients. The aim of this in vivo study was to evaluate coronary atherosclerotic vessel abnormalities and endothelial function using angiography, intravascular ultrasound, and intracoronary acetylcholine infusion. Fourteen patients (11 male, 3 female; mean age 49.3 years) were examined early after heart transplantation (mean interval after transplantation: 11 weeks) because of coronary artery disease (n = 8), idiopathic dilatative cardiomyopathy (n = 7), mitral valve replacement (n: 1) or left atrial filiae of a leiomyosarcoma (n = 1). Mean age of the donor hearts (female n = 8) was 29 years; 3 patients received double- and 14 patients triple-immunosuppression. All patients underwent biplane ventriculography and coronary angiography; a total of 120 coronary segments (main stem 21, left anterior descending artery 85, circumflex artery 14) was examined by intravascular ultrasound (20 MHz, 3.5 F catheters). In 13 patients, acetylcholine was infused into the proximal left anterior descending artery (0.15 microgram/min to 150.0 micrograms/min) to evaluate vasomotion within this segment. Ventriculography demonstrated regional wall abnormalities in 2 patients, angiography revealed 9 noncritical stenotic segments in 5 patients. Intravascular ultrasound detected 52 cross-sectional areas with a three-layer appearance indicating intimal thickening. Mean circumferential expansion of intimal proliferation was 192 degrees and mean intimal thickness was 0.35 mm. Only 5 segments of the sonographically pathological cross-sectional areas showed angiographic evidence of atherosclerotic lesions. After intracoronary infusion at a lower dose (0.15 and 1.5 micrograms/min) of acetylcholine, vasoconstriction was observed in 2 patients, at a dose of 15.0 and 150.0 micrograms/min in 10 patients. This response to acetylcholine did not depend on the intravascular or angiographical extent of atherosclerotic vessel abnormalities. In heart transplant recipients, coronary artery abnormalities can already be depicted at an early stage using intravascular ultrasound. The majority of patients show coronary vasoconstriction following infusion of acetylcholine at a higher dose. Further investigation is necessary to clarify whether the depicted vessel wall abnormalities can already be interpreted as newly developed graft atherosclerosis and whether abnormal vasomotion after acetylcholine is indicative of endothelial dysfunction.