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  • 1
    Electronic Resource
    Electronic Resource
    Über den Einfluß von Mangan-Ionen auf die positiv inotrope Wirkung von Adrenalin, Theophyllin und Digitoxigenin an isolierten Meerschweinchenvorhöfen (1969)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 265 (1969), S. 131-148 
    Details
    ISSN: 1432-1912
    Keywords: Ca-Influx and Manganese ; Adrenaline ; Theophylline ; Digitoxigenin ; Isolated Guinea Pig Auricle ; Ca-Einstrom und Mangan ; Adrenalin ; Theophyllin ; Digitoxigenin ; Isolierter Meersehweinchenvorhof
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of bivalent manganese ions (Mn++) on the positive inotropic effect of adrenaline, theophylline, and digitoxigenin was studied in isolated, electrically driven left guinea-pig auricles in phosphate-free Tyrode's solutions with different extracellular calcium concentrations ([Ca]e; 0.45; 1.8; 7.2 mM). Mn++ (0.1–50 mM) exerted a dose-dependent negative inotropic effect which was dependent on [Ca]e: Raising [Ca]e decreased the inhibitory action of Mn++. The negative inotropic effect of Mn++ was exclusively due to a decrease in the rate of tension development; the time to peak tension and the duration of contraction remained unchanged. In a solution containing 0.45 mM Ca, pretreatment with 0.1 mM Mn+ significantly diminished the positive inotropic effect of adrenaline (10−9-10−5 g/ml) and theophylline (5×10−6-10−3 g/ml), but did not influence the effect of digitoxigenin (2×10−7-2×10−6 g/ml). The depression of the positive inotropic effect of adrenaline and theophylline with higher concentrations of Mn+ (0.35–2.25 mM, producing a negative inotropic effect of about 50%) was influenced by the [Ca]e. The effect of Mn+ was most evident at 0.45 mM Ca, less pronounced (but significant) at 1.8 mM Ca and was not observed at 7.2 mM Ca. With the same concentrations of Mn+, however, the positive inotropic effect of digitoxigenin was only slightly decreased at 0.45 mM Ca, was not changed at 1.8 mM Ca and was increased at 7.2 mM Ca. As Mn+ selectively blocks the inward movement of Ca ions across the membrane of the myocardial cell during depolarisation, it is tentatively concluded from these experiments that the positive inotropic effect of adrenaline and theophylline may be due at least partially to an increase of the Ca influx during the excitation process, whereas the positive inotropic effect of digitoxigenin seems to be independent of this mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00997146
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  • 2
    Electronic Resource
    Electronic Resource
    Über die positiv inotrope Wirkung von Dibutyryl-3′,5′-AMP an isolierten Rattenvorhöfen (1972)
    Springer
    Pflügers Archiv 333 (1972), S. 197-212 
    Details
    ISSN: 1432-2013
    Keywords: Positive Inotropic Effect ; Dibutyryl-3′,5′-AMP ; Isolated Rat ; Atria ; [Ca]e ; Adrenaline and Theophylline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. In isolated electrically driven (frequency 2 Hz) rat left atria the N6-2′-O-dibutyryl derivative of cyclic 3′,5′-AMP (DB-AMP; monosodium salt) produced a concentration-dependent and reversible positive inotropic effect. In normal Tyrode solution (1.8 mM Ca++, the threshold concentration was 5×10−5 M; the peak concentration (10−3 M) increased contractile force to 203% of control values. Negative inotropic responses were not observed in these experiments even with supramaximal DB-AMP concentrations (Fig. 1). 2. The positive inotropic effect of DB-AMP developed gradualy (Fig. 2). It began 0.3–7.7 min after addition of the drug and was maximal within 3.5–28.3 min (Tab. 2). Once established, the effect was prolonged and decreased only slightly within 60 min (Fig. 2). 3. The positive inotropic effect of DB-AMP was due to an increase in the rate of tension development. The time to peak tension and the duration of contraction remained unchanged (Tab. 3). 4. At high concentrations (10−3–5×10−3M) DB-AMP caused contractures in some experiments (Tab. 1). 5. The time course and the magnitude of the inotropic effects of DB-AMP were influenced by the [Ca]e. The increment in myocardial contractility caused by 10−3M DB-AMP developed faster at high than at low [Ca]e (Tab. 4; Fig. 5). On the other hand, the positive inotropic effect of 10−3M DB-AMP was most evident at normal (1.8 mM) and reduced (0.45; 0.9 mM) [Ca]e, less pronounced at 3.6 mM Ca++ and was insignificant at 7.2 mM Ca++ (Fig.3). 6. Sodium butyrate (10−4–10−2M) did not alter the contractile behaviour of isolated rat atria. 7. In isolated electrically driven (frequency 3 Hz) left guinea-pig atria no positive inotropic effects could be demonstrated with DB-AMP at concentrations up to 10−3M. It is concluded that the positive inotropic action of DB-AMP—at least in isolated rat atria—may resemble that of adrenaline or theophylline in some points, e.g. with regard to its dependence on the [Ca]e. But as no positive inotropic effect could be observed in guinea-pig atria and as the mechanism by which DB-AMP augments contractile force remains obscure, the results are not thought to necessarily support the view that the effects of adrenaline or theophylline on contractile behaviour of mammalian cardiac muscle occur via cyclic AMP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00592683
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    Paper (German National Licenses)
    Fulltext
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