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J Brachmann

Publications and source records attributed to J Brachmann.

At least 19 recordsLinked to original sources

K+ channels in cardiomyocytes of the pulmonate snail helix.

We used the patch-clamp technique to identify and characterize the electrophysiological, biophysical, and pharmacological properties of K(+) channels in enzymatically dissociated ventricular cells of the land pulmonate snail Helix. The family of outward K(+) currents started to activate at -30 mV and the activation was faster at more depolarized potentials (time constants: at 0 mV 17.4 +/- 1.2 ms vs. 2.5 +/- 0.1 ms at + 60 mV). The current waveforms were similar to those of the A-type family of voltage-dependent K(+) currents encoded by Kv4.2 in mammals. Inactivation of the current was relatively fast, i.e., 50.2 +/- 1.8% of current was inactivated within 250 ms at + 40 mV. The recovery of K(+) channels from inactivation was relatively slow with a mean time constant of 1.7 +/- 0.2 s. Closer examination of steady-state inactivation kinetics revealed that the voltage dependency of inactivation was U-shaped, exhibiting less inactivation at more depolarized membrane potentials. On the basis of this phenomenon, we suggest that a channel encoded by Kv2.1 similar to that in mammals does exist in land pulmonates of the Helix genus. Outward currents were sensitive to 4-aminopyridine and tetraethylammonium chloride. The last compound was most effective, with an IC(50) of 336 +/- 142 micro mol l(-1). Thus, using distinct pharmacological and biophysical tools we identified different types of voltage-gated K(+) channels.

4-Aminopyridine↗

Is the "candy-wrapper" effect of (32)P radioactive beta-emitting stents due to remodeling or neointimal hyperplasia? Insights from intravascular ultrasound.

A recognized limitation of radioactive stents is the development of restenosis at the stent edges, known as the "candy-wrapper" effect. The mechanisms of this effect remain incompletely understood and controversial. The aim of this study is to assess the effect of endovascular irradiation on neointima formation and vascular remodeling. (32)P Palmaz-Schatz stents (1.5-4 microCi) were implanted in 11 patients with restenosis after previous percutaneous transluminal coronary angioplasty (PTCA). Intravascular ultrasound (IVUS) images of target sites and adjunct vessel segments were acquired both during intervention and after 6 months. The angiographic restenosis rate was 54%, and the MLD decreased from 2.21 +/- 0.6 mm to 1.38 +/- 0.4 mm at follow-up (P < 0.01). IVUS analysis demonstrated that late lumen loss was the result of neointimal tissue proliferation, which was nonuniformly distributed and exaggerated at both the central articulation and the distal stent edges. Negative remodeling did not contribute to restenosis. In contrast, we found a linear relationship between increase of area stenosis and a positive remodeling index (r = 0.84, P < 0.0001). Restenosis after implantation of (32)P Palmaz-Schatz stents was mainly the result of neointimal tissue proliferation which tended to be nonuniformly distributed in the stent articulation and edges. Negative remodeling or stent recoil was not observed. Cathet Cardiovasc Intervent 2001;54:41-48.

Aged↗

Quadruple pads approach for external cardioversion of atrial fibrillation.

This study examined the alternative of transthoracic quadruple pads shock delivery of two simultaneous 360-J shocks to convert refractory AF in patients failing standard external cardioversion. Forty-six patients (mean age 58 +/- 11 years, 23 men) with chronic AF (duration 14 +/- 17 months, range 1-60 months) were included. The left atrial diameter was 47 +/- 7 mm. The left ventricular ejection fraction was 59 +/- 11%. Antiarrhythmic drugs had failed to convert 44 (96%) of these patients. All patients underwent conventional external transthoracic cardioversion with pads applied in the antero-apical position using energy settings of 200 and 360 J, consecutively. In all patients who failed conventional cardioversion, quadruple pads were applied. Quadruple pads consisted of four pads, two in the antero-posterior position and two in a second apex-posterior position. Standard cardioversion to sinus rhythm was successful in 19 (41%) patients after use of a single 200-J shock and an additional 8 (17%) after a single 360-J shock. The total success rate was 58% after conventional cardioversion. The quadruple pads were successful in 14 (74%) of the remaining 19 patients. Four of the five patients who failed the quadruple pads approach subsequently also failed internal cardioversion. Thus, the cardioversion success rate was increased from 48% using the conventional approach to 89% using the quadruple pads approach. Quadruple pads external cardioversion is highly effective in converting chronic AF refractory to standard shock protocols to sinus rhythm. Moreover, the failure of the quadruple pads approach seems to predict poor response to internal cardioversion.

Aged↗

A multicentre, double-blind randomized crossover comparative study on the efficacy and safety of dofetilide vs sotalol in patients with inducible sustained ventricular tachycardia and ischaemic heart disease.

BACKGROUND: Antiarrhythmic drugs are still used for the treatment of ventricular tachyarrhythmias, in combination with implantable cardioverter-defibrillators or without them. AIM OF THE STUDY: In a double-blind randomized crossover design, the short- and long-term efficacy and safety of oral dofetilide or oral sotalol were compared in 135 patients with ischaemic heart disease and inducible sustained ventricular tachycardia. METHODS: The inducibility of ventricular tachycardia was determined by programmed electrophysiological stimulation at baseline. Patients were then blindly randomized to receive either oral dofetilide 500 microg twice daily or oral sotalol 160 mg twice daily, for 3 to 5 days. Suppression of inducible ventricular tachycardia on the drug was then assessed by programmed electrophysiological stimulation. After a wash-out period of at least 2.5 days, the patients received the alternative treatment for 3 to 5 days. Suppression of inducible ventricular tachycardia on the alternate drug was again determined by programmed electrophysiological stimulation. Selection of long-term treatment was allocated blindly according to programmed electrophysiological stimulation results. RESULTS: During the acute phase, 128 patients received both dofetilide and sotalol. Sixty-seven patients were responders to either drug. Forty-six patients (35.9%) were responders to dofetilide compared with 43 (33.6%) to sotalol (P=ns). Only 23 patients responded to both dofetilide and sotalol. Adverse events, deemed to be treatment related, were seen in 2.3% of patients receiving dofetilide and 8.6% of patients receiving sotalol (P=0.016). Three patients on dofetilide had torsade de pointes. Two patients receiving sotalol died during the acute phase (one was arrhythmic death, and the other was due to heart failure). During the long-term phase, two of 42 patients (4.8%) receiving dofetilide and three of 27 patients (11.1%) receiving sotalol withdrew from treatment due to lack of efficacy. Overall, during the long-term phase, 23.8% of the patients receiving dofetilide and 37.0% of the patients receiving sotalol, withdrew from treatment with a similar pattern of withdrawals for the two drugs. CONCLUSION: Dofetilide was as efficacious as sotalol in preventing the induction of sustained ventricular tachycardia. There was no concordance in the response rate in two-thirds of the patients. Dofetilide was significantly better tolerated during the acute phase than sotalol. Both dofetilide and sotalol were well tolerated during the long term with no statistically significant difference in the adverse events.

Adult↗

Heart rate dynamics at the onset of ventricular tachyarrhythmias as retrieved from implantable cardioverter-defibrillators in patients with coronary artery disease.

BACKGROUND: The recent availability of implantable cardioverter-defibrillators (ICDs) that record 1024 R-R intervals preceding a ventricular tachyarrhythmia (VTA) provides a unique opportunity to analyze heart rate variability (HRV) before the onset of VTA. METHODS AND RESULTS: Fifty-eight post-myocardial infarction patients with an implanted ICD for recurrent VTA provided 2 sets of 98 heart rate recordings in sinus rhythm: (1) before a VTA and (2) during control conditions. Three subgroups were considered according to the antiarrhythmic (AA) drug regimen. A state of sympathoexcitation was suggested by the significant reduction in HRV before VTA onset compared with control conditions. beta-Blockers and dl-sotalol enhanced HRV in control recordings; nevertheless, HRV declined before VTA independent of AA drugs. A gradual increase in heart rate and decrease in sinus arrhythmia at VTA onset were specific findings of patients who received dl-sotalol. CONCLUSIONS: The peculiar heart rate dynamics observed before VTA onset are suggestive of a state of sympathoexcitation that is independent of AA drugs.

Adrenergic beta-Antagonists↗

Isoproterenol specifically modulates reverse rate-dependent effects of d,l-sotalol, d-sotalol, and dofetilide.

The modulation of antiarrhythmic and proarrhythmic properties of antiarrhythmic compounds by increased sympathetic activity is of experimental and clinical interest. However, the interaction of adrenergic stimulation with the rate-response pattern of class III antiarrhythmic agents is not well established. Using standard microelectrode techniques, we evaluated the effects of isoproterenol (iso) on the action of d,l-sotalol (d,l-sot), d-sotalol (d-sot), and dofetilide (dof) on action-potential parameters recorded from isolated canine cardiomyocytes. The cell-isolation procedure was performed from the endocardial layers of left ventricular myocardium from healthy beagle dogs. The following electrophysiologic parameters were recorded: resting membrane potential (RMP), action-potential amplitude (APA), action-potential duration at 90% repolarization (APD 90), and effective refractory period (ERP). After exposure to iso, the class III activity of d,l-sot was well maintained over the entire range of frequencies studied. In contrast, iso differentially antagonized the action of d-sot and dof. In comparison to dof, the class III action of d-sot was particularly sensitive to iso, predominantly at faster stimulation rates. Our observations demonstrate specific rate regulation of the class III action of d,l-sot, d-sot, and dof in response to adrenergic stimulation. The unfavorable rate-response pattern of d-sot compared with d,l-sot and dof might prove disadvantageous in high-catecholamine states.

Action Potentials↗

The role of class III antiarrhythmic agents in maintaining sinus rhythm.

The last decade has seen considerable changes in both attitude and approach to the management of arrhythmia. Much of this has resulted from trials such as the CAST (Cardiac Arrhythmia Suppression Trial) and the CASH (Cardiac Arrhythmia Study Hamburg), which demonstrated the potentially lethal consequences of using class I sodium channel blockers in patients with structural heart disease. The subsequent popularity of the class III agents and recognition that they are the best available therapy has led to the popularity of amiodarone and sotalol in the treatment of arrhythmia. Although these agents can achieve good efficacy in the suppression of atrial fibrillation their use is not without problems. Sotalol requires careful patient selection due to the risk of proarrhythmia and although cardiac effects are rare with amiodarone therapy, potentially serious non-cardiac adverse effects can limit the long-term use of this agent. Although treatment guidelines have helped to clarify our current knowledge and outline appropriate clinical application of antiarrhythmic agents, the need for antiarrhythmic agents which marry efficacy with improved safety and clinical applicability is apparent.

Amiodarone↗

Intravascular ultrasound for evaluation of initial vessel patency and early outcome following directional coronary atherectomy.

Elastic recoil and thrombus formation may potentially occur following directional coronary atherectomy (DCA) confounding the assessment of late vascular remodeling. Since intravascular ultrasound (IVUS) data on early outcome of DCA is not available, we used IVUS to investigate whether elastic recoil or thrombus formation can affect early (4 hr) outcome. Quantitative coronary angiography (QCA) and IVUS were performed in high-grade coronary lesions in 32 consecutive patients before, immediately after, and 4 hr after DCA. Late clinical follow-up was obtained after a maximum interval of 2 years. Significant acute elastic recoil was observed by both IVUS (19%+/-14%) and QCA (19%+/-12%), but there was no further recoil after 4 hr. DCA reduced plaque area by 51%+/-13%, an effect that was stable after 4 hr, indicating the absence of relevant thrombus formation. Residual area stenosis by IVUS was not related to the occurrence of late clinical events (n = 8). Mechanical recoil or thrombus formation do not hamper initial lumen gain achieved by DCA. Although QCA significantly underestimated residual plaque burden after DCA when compared to IVUS, the degree of residual area stenosis did not identify patients suffering from cardiac events on follow-up.

Aged↗

Effects of the Ikr-blocker almokalant and predictors of conversion of chronic atrial tachyarrhythmias to sinus rhythm. A prospective study.

PURPOSE: To assess the efficacy of the Ikr-blocker almokalant attempting to convert chronic atrial tachyarrhythmias, and to find predictors of conversion, to sinus rhythm. METHODS: The electrophysiological effects of a 6-hour infusion of almokalant, to a total dose of 25 +/- 4 mg, were assessed by ECG and transesophageal atrial electrograms (TAE) in 100 consecutive patients with atrial fibrillation/flutter (n = 95/5) of 8 +/- 12 months' duration (range 1 to 99 months). RESULTS: The conversion rate was 32%. The time to conversion was 3.5 +/- 2.2 hours. During infusion increases in QTtop (292 +/- 35 to 335 +/- 44 ms, p < 0.001, after 30 minutes), QT (387 +/- 40 to 446 +/- 60 ms, p < 0.001), corrected QT (425 +/- 30 to 487 +/- 44 ms, p < 0.001), and QT dispersion (21 +/- 12 to 29 +/- 31 ms, p = 0.02), were paralleled by decreases in T wave amplitude (0.31 +/- 0.19 to 0.23 +/- 0.16 mV, p < 0.001), and atrial rate (425 +/- 78 to 284 +/- 44 beats per minute (bpm) on ECG, and 396 +/- 72 to 309 +/- 44 bpm on TAE), with no differences between converters to sinus rhythm and non-converters. Patients with aberrantly conducted beats, and T wave variation, also increased. Calcium antagonists were more common among converters. A decreasing T wave amplitude predicted conversion. Four patients developed torsades de pointes. CONCLUSIONS: This study demonstrates class III action of almokalant, with a conversion rate of 32% of long-standing, chronic atrial tachyarrhytmias. An early decrease in T wave amplitude was associated with conversion to sinus rhythm.

Aged↗

Rate and time dependent effects of D-sotalol on the monophasic action potential after sudden increase of the heart rate.

Experimental and clinical data suggests that almost all Class III antiarrhythmic agents diminish their ability to prolong cardiac repolarization at fast heart rates. However, only limited data exists about the time course of efficacy decay of Class III agents after sudden increase of the heart rate. In the present study, we assessed both rate and time dependent changes of the efficacy of d-sotalol in higher stimulation frequencies following an abrupt increase in heart rate. This might imitate the situation seen in the development of paroxysmal tachycardias. Monophasic action potentials were recorded from the right ventricular apex during sinus rhythm and constant stimulation with the paced cycle length (PCL) of 550 ms, 400 ms, and 330 ms in the baseline and 20 minutes after intravenous administration of d-sotalol (2.5 mg/kg) in seven patients with documented life-threatening ventricular tachyarrhythmias. D-sotalol significantly prolonged monophasic action potential duration at different steady-state heart rates (sinus rhythm: 21.1% +/- 3.6%; PCL 550 ms: 16.6% +/- 4.3%, 400 ms: 11.2% +/- 2.7%, 330 ms: 5.8% +/- 2.1%). The prolongation is significantly shorter in higher steady-state pacing, confirming a pronounced reverse-use dependent decrease of the efficacy of d-sotalol at faster stimulation frequencies. After the abrupt increase in heart rate, the beat-to-beat adaptation of the postdrug action potential prolongation exhibits only slight reverse-use dependent shortening. The decrease of the efficacy of d-sotalol is insignificant for the first 20 consecutive beats at the stimulation frequency of the PCL of 400 msec (from 16.6% at PCL of 550 ms to 14.6% at the 20th beat of the PCL of 400 ms), and for the first ten consecutive beats at the stimulation frequency of the PCL of 330 ms (from 16.8% at PCL of 550 ms to 12.3% at the 10th beat of the PCL of 330 ms). This slow decay of action potential prolongation after an abrupt increase in heart rate might contribute to the antiarrhythmic action of d-sotalol in cardiac tachyarrhythmias.

Action Potentials↗

HERG potassium channel activation is shifted by phorbol esters via protein kinase A-dependent pathways.

We investigated the effects of the phorbol ester phorbol 12-myristate 13-acetate (PMA) on the rapid component of the delayed rectifier potassium current, IKr, in guinea pig cardiomyocytes and found that the IKr current amplitude was reduced by 20% with 10 nM PMA and 44% with 100 nM PMA. The ether-a-go-go-related gene (HERG) encodes IKr in human heart. We expressed HERG heterologously in Xenopus oocytes and investigated the effects of PMA on the delayed rectifier potassium current. Upon application of PMA in a concentration of 100 nM, we found a similar reduction of HERG outward current amplitude by 59%. This reduction was due to a shift in the HERG activation curve by 37 mV. The ED50 for the PMA-induced shift was 9.0 nM. The inactive 4alpha-phorbol 12-myristate 13-acetate (4alpha-PMA) had no effect. PMA is known to act by stimulating distinct protein kinase cascades. Additional application of the specific protein kinase C inhibitors chelerythrine (10 microM) or bisindolylmaleimide (1 microM) could not attenuate the PMA-induced shift. In contrast, the shift by PMA was reduced significantly when the specific protein kinase A (PKA) inhibitors H89 (50 microM) or KT5720 (2.5 microM) were applied. Forskolin (400 microM), an activator of the adenylate cyclase that results in PKA activation, shifted the HERG activation curve by 14 mV. Moreover the specific protein kinase C activator 1-stearoyl-2-arachidonylglycerol (10 microM) showed no effect. Our data suggest that mainly PKA is mediating the shift of the HERG activation kinetics.

Alkaloids↗

Improved clinical effectiveness with a collagen vascular hemostasis device for shortened immobilization time following diagnostic angiography and percutaneous transluminal coronary angioplasty.

This study prospectively compared immobilization time followed by use of a vascular hemostasis device (VasoSeal) versus manual compression to achieve hemostasis at the arterial puncture after angiography and percutaneous transluminal coronary angioplasty (PTCA). The trial shows that use of a vascular hemostasis device results in earlier mobilization, even in highly anticoagulated PTCA patients compared with manual compression, with no statistically significant complications.

Adolescent↗

Differential effects of d, l-sotalol and d-sotalol on isoproterenol-increased delayed rectifier outward potassium current in guinea pig single ventricular myocytes.

The aim of this study was to compare the effects of d, l-sotalol and d-Sotalol on the delayed rectifier K+ outward current in the presence of isoproterenol at different concentrations. Time-dependent delayed rectifier K+ outward currents were measured in isolated guinea pig single myocytes using the whole-cell configuration of the patch-clamp technique. Currents were measured in response to 300 ms depolarizing pulses from a holding potential of -40 mV in three experimental protocols [control, isoproterenol (10(-9) mol/L-10(-6) mol/L), and isoproterenol (10(-9) mol/L-10(-6) mol/L) plus either d, l-Sotalol (10(-4) mol/L) or d-Sotalol (10(-4) mol/L)]. IK tail currents were measured upon repolarization to -40 mV. It was found that IK was significantly amplified in the presence of isoproterenol (10(-9) mol/L-10(-6) mol/L) plus d-Sotalol. At 10(-8) mol/L isoproterenol, IK was increased by 92.7% +/- 17.1% (P < 0.05) and 54.3% +/- 13.4% after d-Sotalol addition (P < 0.05). In contrast, d, l-Sotalol completely conteracted the increase of Ik by isoproterenol (< 10(-8) mol/L), and compared to control, IK was decreased by 35.6% +/- 8.1% at 10(-8) mol/L isoproterenol plus d, l-Sotalol (P < 0.05). It is concluded that the beta-adrenergic blocking property of d, l-Sotalol but not that of d-Sotalol maintains the delayed rectifier K+ outward current blockade in the presence of isoproterenol in guinea pig myocytes. This might contribute to a superior antiarrhythmic efficacy as compared to d-Sotalol.

Adrenergic beta-Agonists↗

[Prevention and treatment of restenosis after percutaneous transluminal coronary angioplasty].

Restenosis is a clinical problem after coronary angioplasty associated with major ischemic events or repeat interventions in 20-50% of the patients undergoing this procedure. Major efforts have been undertaken in the past decade to successfully prevent or treat restenosis but no pharmacologic approach to the problem has as yet been identified to be effective enough in clinical conditions. New strategies to cope with restenosis are targeted by local application of ionizing radiation which markedly reduces cell proliferation after angioplasty in animal experiments. Preliminary clinical trials indicate that endovascular radiation therapy is a safe and effective means to treat restenosis. Randomized, multicenter studies with long follow-up periods are needed to support these early results.

Angioplasty, Balloon, Coronary↗

[Catheter-assisted techniques for decreasing the rate of restenosis after coronary angioplasty: an overview of radiotherapy].

Restenosis after percutaneous transluminal coronary angioplasty (PTCA) is a clinical problem associated with major ischemic events or repeat interventions in 20-50% of the treated patients. Systemic drug therapy has not yet been shown to prevent restenosis in clinical conditions. However, local therapeutic strategies are evolving, such as the catheter-based delivery of drugs, of antiproliferative genes, or of ionizing radiation. Experimental studies show that radiation therapy reduces restenosis rates, and preliminary clinical trials investigating a small number of patients indicate that, in particular, catheter-based radiation may be safe and effective. Randomized multicenter studies with long follow-up periods are needed to support these early results.

Angioplasty, Balloon, Coronary↗

Differential rate and potassium-dependent effects of the class III agents d-sotalol and dofetilide on guinea pig papillary muscle.

The class III agents d-sotalol and dofetilide have been shown to exhibit differential effects in large controlled clinical trials. The aim of this study was to investigate the basic electrophysiological properties of these two antiarrhythmia agents in an in vitro experimental model with regard to potential antiarrhythmic and proarrhythmic action. Using standard microelectrode techniques, we evaluated the electrophysiological effects of d-sotalol and dofetilide on action potential parameters recorded from guinea pig papillary muscle at 2.5 mM, 3.5 mM, and 5.6 mM extracellular potassium concentrations. The following parameters were recorded: resting membrane potential (RMP), action potential amplitude (APA), action potential duration at 90% repolarization (APD 90), and maximum upstroke velocity (Vmax). Under all conditions studied, both d-sotalol and dofetilide exhibited highly selective reverse rate-dependent class III action. In contrast to dofetilide, the class III activity of d-sotalol was markedly influenced by changes in extracellular potassium concentrations, predominantly at low pacing rates. Hypokalemia enhanced the action potential-prolonging effects of d-sotalol, whereas hyperkalemia diminished this effect. In addition, reverse rate dependence associated with dofetilide was significantly more pronounced than reverse rate dependence associated with d-sotalol. Our observations provide a potential electrophysiological basis for differential antiarrhythmic and proarrhythmic mechanisms associated with these two drugs.

Action Potentials↗