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  • 2005-2009
  • 1995-1999  (3)
  • 1945-1949
  • Use dependence  (2)
  • Angeborene Herzfehler  (1)
  • 1
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Sheep cardiac Purkinje fibre ; Voltage-clamp ; Pacemaker current ; Use dependence ; Specific bradycardic agent ; ZD 7288
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00168917
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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    Artikel (Nationallizenzen)
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  • 2
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Key words Sheep cardiac Purkinje fibre ; Voltage-clamp ; Pacemaker current ; Use dependence ; Specific bradycardic agent ; ZD 7288
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00168917
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 3
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): 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
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: 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.
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001120050541
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
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