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  • Use dependence  (2)
  • (−)-noradrenaline  (1)
  • Antiarrhythmic therapy  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Inhibition of pacemaker current by the bradycardic agent ZD 7288 is lost use-dependently in sheep cardiac Purkinje fibres (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1995), S. 64-72 
    Details
    ISSN: 1432-1912
    Keywords: Sheep cardiac Purkinje fibre ; Voltage-clamp ; Pacemaker current ; Use dependence ; Specific bradycardic agent ; ZD 7288
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The inhibition of the pacemaker current (i f) in sheep cardiac Purkinje fibres by ZD 7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium chloride] is lost use-dependently. This disinhibition of i f was investigated by using the two-microelectrode voltage-clamp technique. The pulse protocol consisted of a rest period (holding potential of about -50 mV, 1–10 μmol/l ZD 7288) followed by a train of test pulses (potential negative to -100 mV, stimulation frequency 0.05 Hz). At the beginning of the first test pulse there was an immediate reduction of i f but inhibition was lost during continued stimulation. Activation of i f is sigmoidal and the early delay in current activation was prolonged from 33 ms (no ZD 7288) to 424 ms (10 μmol/l ZD 7288). Therefore hardly any disinhibition occurred during short test pulses (0.5 s). During longer test pulses (5 s, -120 mV, 10 μmol/l) disinhibition developed with a time constant of about 2 s. The inhibition of i f by ZD 7288 was lost voltage-dependently. With 10 μmol/l ZD 7288 the half-maximal disinhibition occurred at -92 mV and the slope factor of the disinhibition/voltage curve (Boltzmann relation) was 4.8 mV. The voltage-dependent disinhibition could be abolished largely by extracellular application of protease (0.5 mg/ml, 7 min). After prior disinhibition, reinhibition at the holding potential (about -50 mV) followed a bi-exponential time course indicating that inhibition may be produced by a fast (τ=0.7 min) and a slow component (τ=20–30 min). Increasing ZD 7288 concentration from 1 to 10 μmol/l accelerated reinhibition, mainly by an increase of the amplitude (A) of the fast component. The ratio A fast/A sIow was 0.399 at 1 μmol/l and 2.65 at 10 μmol/1 ZD 7288. The reinhibition of i f was unchanged by shifting the holding potential from -50 mV to -20 mV Trials to wash out the effects of 10 μmol/l ZD 7288 gave two results. The inhibition of i f was slightly reversed after a wash-out of 1.5 h with drug-free solution. A second effect of the drug, the fast reinhibition, could be completely removed by washout. In summary i f is inhibited by ZD 7288 at membrane potentials at which the virtual i f gate is closed. Disinhibition occurs during long-lasting hyperpolarization but will hardly be operative in unclamped fibres under physiological conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168917
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Inhibition of pacemaker current by the bradycardic agent ZD 7288 is lost use-dependently in sheep cardiac Purkinje fibres (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1995), S. 64-72 
    Details
    ISSN: 1432-1912
    Keywords: Key words Sheep cardiac Purkinje fibre ; Voltage-clamp ; Pacemaker current ; Use dependence ; Specific bradycardic agent ; ZD 7288
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The inhibition of the pacemaker current (i f) in sheep cardiac Purkinje fibres by ZD 7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium chloride] is lost use-dependently. This disinhibition of i f was investigated by using the two-microelectrode voltage-clamp technique. The pulse protocol consisted of a rest period (holding potential of about –50 mV, 1–10 μmol/l ZD 7288) followed by a train of test pulses (potential negative to –100 mV, stimulation frequency 0.05 Hz). At the beginning of the first test pulse there was an immediate reduction of i f but inhibition was lost during continued stimulation. Activation of i f is sigmoidal and the early delay in current activation was prolonged from 33 ms (no ZD 7288) to 424 ms (10 μmol/l ZD 7288). Therefore hardly any disinhibition occurred during short test pulses (0.5 s). During longer test pulses (5 s, –120 mV, 10 μmol/l) disinhibition developed with a time constant of about 2 s. The inhibition of i f by ZD 7288 was lost voltage-dependently. With 10 μmol/l ZD 7288 the half-maximal disinhibition occurred at –92 mV and the slope factor of the disinhibition/voltage curve (Boltzmann relation) was 4.8 mV. The voltage-dependent disinhibition could be abolished largely by extracellular application of protease (0.5 mg/ml, 7 min). After prior disinhibition, reinhibition at the holding potential (about –50 mV) followed a bi-exponential time course indicating that inhibition may be produced by a fast (τ=0.7 min) and a slow component (τ=20–30 min). Increasing ZD 7288 concentration from 1 to 10 μmol/l accelerated reinhibition, mainly by an increase of the amplitude (A) of the fast component. The ratio A fast/A slow was 0.399 at 1 μmol/l and 2.65 at 10 μmol/l ZD 7288. The reinhibition of i f was unchanged by shifting the holding potential from –50 mV to –20 mV. Trials to wash out the effects of 10 μmol/l ZD 7288 gave two results. The inhibition of i f was slightly reversed after a wash-out of 1.5 h with drug-free solution. A second effect of the drug, the fast reinhibition, could be completely removed by wash-out. In summary i f is inhibited by ZD 7288 at membrane potentials at which the virtual i f gate is closed. Disinhibition occurs during long-lasting hyperpolarization but will hardly be operative in unclamped fibres under physiological conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168917
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Multifokale atriale Tachykardie im Kindesalter Darstellung zweier Fallbeispiele und Übersicht über die Literatur (1999)
    Springer
    Monatsschrift Kinderheilkunde 147 (1999), S. 1074-1080 
    Details
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Multifokale atriale Tachykardie (MAT) ; Chaotische Vorhoftachykardie ; Antiarrhythmische Therapie ; Säugling ; Angeborene Herzfehler ; Key words Multifocal atrial tachycardia (MAT) ; Chaotic atrial rhythm ; Antiarrhythmic therapy ; Infancy ; Congenital heart defects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Definition: Multifocal atrial tachycardia (MAT) (also called chaotic atrial rhythm or mechanism) is a rare rhythm disturbance in infancy and childhood. It usually occurs as a sequela of chronic obstructive lung disease in adults with an incidence of about 0,5% and a high mortality rate. In infancy, the incidence has been estimated to be about 0,2%, mainly found in young infants. Diagnosis: It is characterized by an atrial frequency greater than 100 per minute, 3 or more different p-wave contours, variable PP, RR and PR-intervals, and a discrete isoelectric baseline. The origin of the arrhythmia remains unclear but atrial distension may play a significant role. Discussion: We report on the clinical course and management of two patients and also review the relevant literature.
    Notes: Zusammenfassung Definition: Die multifokale atriale Tachykardie (MAT) bzw. chaotische atriale Tachykardie oder chaotische Vorhoftachykardie ist im Kindesalter selten. Im Erwachsenenalter ist sie vorwiegend bei Patienten mit akuten oder chronischen Lungenerkrankungen beschrieben und mit einer hohen Letalität behaftet. Im Gegensatz zum Auftreten im Erwachsenenalter besitzt die MAT im Kindesalter durchweg eine gute Prognose. Diagnose: Elektrokardiographisch ist die MAT durch mindestens 3 unterschiedlich konfigurierte P-Wellen charakterisiert, die nicht der elektrischen Sinusachse entsprechen. Es besteht eine isoelektrische Linie zwischen den P-Wellen, die Vorhoffrequenz beträgt normalerweise mehr als 100 Schläge/min mit variablen P-P-, P-R- und R-R-Intervallen. Die Genese dieser Tachyarrhythmie ist unklar, eine Vorhofbelastung als Auslöser ist jedoch wahrscheinlich. Diskussion: Die möglichen Ursachen und Therapiestrategien bei chaotischer Vorhoftachykardie werden anhand zweier Kasuistiken diskutiert und eine Übersicht über die vorliegende Literatur gegeben.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001120050541
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  • 4
    Electronic Resource
    Electronic Resource
    Modulation of pacemaker activity in sheep cardiac Purkinje fibers by stimulation of β-adrenoceptor subtypes (1997)
    Springer
    Basic research in cardiology 92 (1997), S. 25-34 
    Details
    ISSN: 1435-1803
    Keywords: Sheep cardiac Purkinje fibers ; action potentials ; automaticity ; β1-β2- ; adrenoceptors-(−) ; isoproterenol ; (−)-noradrenaline ; procaterol ; bisoprolol ; ICI 118,551
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The electrophysiological effects mediated by β1- and β2- in spontaneously active sheep cardiac Purkinje fibers were investigated using the non-selective agonist (−)-isoproterenol (IPN) and the selective agonists (−)-noradrenaline (β1) and procaterol (β2) in the absence and presence of the selective antagonists bisoprolol (β1) and ICI 118,551 (β2). IPN (0.01 μmol/l) increased the spontaneous rate by 54% and the slope of diastolic depolarization by 68% of the respective control values. Further, IPN increased the action potential duration at −20 mV (APD −20 mV) from 96 to 154 ms, reduced the APD −70 mV by 17% and the duration of the diastole by 39% and slightly hyperpolarized the maximum diastolic potential. These effects were partially inhibited by ICI 118,551 (0.03 μmol/l), diminished by bisoprolol (0.1 μmol/l) and almost completely blocked by the combination of both antagonists. Concentration response curves of IPN were influenced by the selective antagonists as follows: ICI 118,551 (0.03 μmol/l) shifted the curves to the right by 0.2–0.4 log units and increased the slope factor. Bisoprolol (0.1 μmol/l) induced a greater shift to the right by 1.1–1.5 log units. Combination of bisoprolol with ICI 118,551 shifted the curves to the right by 1.5–1.7 log units. Noradrenaline (0.3 μmol/l) elicited similar actions as IPN. Bisoprolol (0.1 μmol/l) shifted the concentration response curves of noradrenaline to the right by 1.1–1.9 log units. Actions of procaterol (0.1 μmol/l) were weak, attained only 15–35% of the maximal effects of IPN and could be blocked by ICI 118,551 (0.03 μmol/l). These results show that the increase of pacemaker activity induced by catecholamines in sheep cardiac Purkinje fibers is predominantly mediated by stimulation of β1. However, contribution of β2 mediated effects could be demonstrated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00803754
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    Paper (German National Licenses)
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