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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 290 (1975), S. 49-68 
    ISSN: 1432-1912
    Keywords: Verapamil ; D 600 ; Cardiac Muscle ; Amplitude-Frequency Relation ; Staircase Phenomena
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A pattern analysis of inotropic actions was carried out on isotonically shortening cat papillary muscles exposed to (±)-verapamil and (±)-D 600 and compared to other Ca-antagonistic interventions. 1. (±)-Verapamil (1–5 μg/ml) leaves contraction amplitudes nearly unchanged at 6/min, whereas at 60/min more than 90% depression (5 μ/ml) occurs. (±)-D 600 is about twice as effective as (±)-verapamil. 2. An increase of [Ca2+]0 in the presence of (±)-verapamil or (±)-D 600 does not restitute the normal amplitude-frequency relationship. There is only a shift toward higher contraction amplitudes. 3. (±)-Verapamil and (±)-D 600 lead to typical biphasic inotropic transients after step changes of the driving rhythm. First a fast and (at higher frequencies) very pronounced negative staircase occurs, followed by a rather slowly developing positive staircase. 4. These drug effects contrast to the effects of lowering [Ca2+]0 or of adding Ni2+ or La3+, which all produce a rather uniform depression of contraction amplitudes at all frequencies and do not elicit staircase phenomena such as seen under the influence of (±)-verapamil or (±)-D 600. 5. In contrast to the action of Ni2+, La3+ or low [Ca2+]0, (±)-verapamil slows down the restitution kinetics of Ca-reavailability from internal stores as determined by the amplitude of test contractions elicited after various periods of rest. 6. Drug-induced changes in the time course of the transmembrane action potential as depending on frequency may partially but not fully explain the contractile phenomena. 7. Possible interpretations as to the sites where (±)-verapamil or (±)-D 600 interferes with cardiac excitation-contraction coupling are given by the aid of a multicompartment model. This model describes excitation-contraction coupling in terms of transmembrane and intracellular Ca-movements.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 290 (1975), S. 69-80 
    ISSN: 1432-1912
    Keywords: Verapamil ; D 600 ; Optical Isomers ; Cardiac Muscle ; Inotropic Effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary On isotonically contracting cat papillary muscles using pattern analysis, a comparison of the effects of the optical isomers of verapamil and D 600 and the racemic drugs was periormed. 1. (-)-verapamil (0.2–0.3 μg/ml) and (-)-D-600 (0.1 μg/ml–3.0 μg/ml) leave the steady state contraction amplitudes nearly, unchanged at 6/min, but produce a strong depression at 60/min. (-)-D 600 is about 8 times as effective as (-)-verapamil. The (+)-isomers exert only a moderate negative inotropic effect (particularly at low frequencies). 2. Increase of [Ca2+]0 does not restitute the normal amplitude-frequency relationship during exposure to either the (-)-isomers or the (+)-isomers. 3. The (-)-isomers lead to typical biphasic staircases after step changes of frequency. A fast negative staircase occurs first followed by a rather slowly developing positive staircase. In contrast, the (+)-isomers have little influence on the usual staircase pattern. 4. The strength-interval relationship for single test contractions elicited after frequent conditioning stimulation indicated that the (-)-isomers probably slow the restitution of intracellular Ca-reavailability. The (+)-isomers have no such effects. 5. The effects produced by the (±)-compounds correspond qualitatively to those of the (-)-isomers. 6. The very different patterns of inotropic actions observed indicate that the (-)- and (+)-isomers of verapamil and D 600 probably interfere with cardiac excitation-contraction coupling at different sites.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2013
    Keywords: Cardiac Muscle ; Relaxation in the Cold ; Ca++-Ions ; Sarcoplasmic Reticulum ; Herzmuskel ; Erschlaffung bei Abkühlung ; Calcium-Ionen ; Sarkoplasmatisches Reticulum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In isolated papillary muscles or auricles or guinea pigs membrane excitability and impulse conductivity will persist for some time even at a temperature as low as 0°C if the Ca-content of the medium is increased to 14.4 mM/l. This peculiarity allowed the study of temperature dependence of action potential, isometric tension development and relaxation velocity of mammalian myocardium in a range between 0°C and 10°C which was hitherto reserved for frog muscle physiology. The principal result was that below 8°C the relaxation process of mammalian myocardium is particularly slowed so that a maximalQ 10 of about 9 could be observed whereas theQ 10 for the rising phase of the mechanogram amounted to about 2 (±0.2) over the whole range between 1°C and 14°C. It is concluded that in a Ca rich medium of low temperature the Ca-binding capacity of the vesicular components of the sarcoplasmic reticulum becomes insufficient by two reasons: (a) The passive influx or liberation of free Ca ions will be enhanced in the cold due to the prolongation of action potential. (b) The active reabsorption of Ca ions into the vesicles by means of an ATP-driven Ca pump—which is essential for relaxation—is depressed by cooling.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2013
    Keywords: Heart Muscle ; Cardiac Muscle ; Excitation-Contraction-Coupling ; Duration of Action Potential ; Paired Pulse Stimulation ; Sarcoplasmic Reticulum ; Herzmuskel ; Elektromechanische Koppelung ; Aktionspotential-Dauer ; paarige Stimulation ; sarkoplasmatisches Reticulum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An isolierten Präparaten des Ventrikelmyokards vom Frosch und von verschiedneen Säugetieren (Papillarmuskeln von Katzen, Kaninchen, Meerschweinchen und Rhesusaffen) wurde mit Hilfe einer Saccharose-Trennwand die Aktionspotentialdauer durch konstante Gleichstromimpulse verändert und der Einfluß auf das isometrische Mechanogramm untersucht. Folgende Ergebnisse wurden erhalten: Im Säugetiermyokard erstreckt sich die mechanische Antwort auf die Beeinflussung eines einzelnen Aktionspotentials über mehrere Kontraktionscyclen. Einmalige anodische Abkürzung der Aktionspotential-Dauer reduziert dabei die zugehörige Kontraktion durch Verkürzung der mechanischen Anstiegszeit nur geringfügig, während die folgende Kontraktion mit unbeeinflußtem Aktionspotential durch Reduktion der Anstiegsgeschwindigkeit beträchtlich abgeschwächt wird. Kathodische Aktionspotential-Verlägerung besitzt den umgekehrten Effekt, d.h. die zugehörige Kontraktion wird infolge Verlängerung der Anstiegszeit nur wenig verstärkt, während das folgende normale Aktionspotential eine wesentlich kräftigere Kontraktion mit erhöhter Anstiegsgeschwindigkeit auslöst. Bei fortgesetzter Veränderung der Aktionspotential-Dauer summieren sich die negativ bzw. positiv inotropen Nachwirkungen. Die Entwicklung und Rückbildung bis zum steady state umfaßt unabhängig von der Frequenz jeweils 5–7 Schläge. Mit steigender extracellulärer Ca++-Konzentration (bis 5,4 mM/l) nimmt die inotrope Wirkung der Aktionspotential-Dauer auf das Mechanogramm beim ersten Schlag zu, im steady state dagegen ab. Im Froschmyokard wird unter den gleichen Bedingungen jeweils nur die zugehörige Kontraktion beeinflußt, wobei sich die mechanische Anstiegszeit und die Anstiegsgeschwindigkeit gleichzeitig ändern. Die unterschiedlichen Reaktionsformen des Frosch- und des Säugetiermyokards erklären auch das differente Verhalten bei alternierender Veränderung der Aktionspotential-Dauer sowie bei paariger Stimulation. Sie werden als funktioneller Ausdruck der unterschiedlichen Feinstruktur im Bereich des sarkoplasmatischen Reticulums beider Gewebe gedeutet.
    Notes: Summary In isolated preparations of the frog's and the mammalian ventricular myocardium (papillary muscles of cat, rabbit, guinea pig, and rhesus monkey) the duration of the action potential was altered by constant current pulses applied through a sucrose gap. The isometric mechanical response of the polarized muscle section was recorded simultaneously. The following results were obtained: In the mammalian myocardium the contractile response to alteration of one single action potential lasts for several contraction cycles. Shortening of the action potential by anodal current polarization reduces the peak tension of the corresponding contraction only by shortening of the time to peak. The amplitude of the following contraction, however, initiated by a normal action potential, is even more depressed, due to a decreased rate of tension development. Prolongation of the action potential by cathodal pulses has an opposite effect. If the duration of the action potential is altered repeatedly, summation of the delayed negative or positive inotropic responses occurs. Independent of the frequency of stimulation, 5 to 7 beats are necessary for the development as well as the restitution of a steady state. With increasing extracellular Ca++ concentration (up to 5,4 mM/l) the inotropic effects are more pronounced with the first beat, bur are decreased in the steady state. In the frog's myocardium, the contractile response to alterations of the duration of the action potential is limited to the corresponding contraction. The mechanical time to peak and the rate of tension development are influenced simultaneously. The differences between the mechanical response of mammalian and frog's myocardium may explain the different contractile reactions accompanying alternating changes of the duration of the action potential as well as paired pulse stimulation. They are considered as a functional manifestation of some differences of the ultrastructure of the sarcoplasmic reticulum in both tissues.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 332 (1972), S. 96-116 
    ISSN: 1432-2013
    Keywords: Displacement Effects ; Cardiac Active State ; Control of Contractility ; Quick Release ; Quick Stretch ; Excitation-contraction Coupling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An investigation was carried out on isolated cat's papillary muscle in order to study displacement effects upon the intensity and the time course of the contractile activity. Displacements occurring before or very early during a contractile cycle produce effects which can be entirely explained on the basis of the cardiac active length-tension relation. Displacements occurring later exhibit additional effects in so far as either stretches or releases induce a drop of contractile activation such that the course of the subsequent tension development is markedly below that of the same displacement applied earlier. In order to separate these effects from those based on the active length-tension correlation experiments were performed in which very short release-stretch or stretch-release operations were applied so that the muscle length was virtually the same at the beginning and at the end of the operation. The results obtained under these conditions can be summarized as follows. The extend to which contractile tension drops after a stretch-release or a release-stretch cycle has been applied depends upon (1) the stimulus intervention interval (2) the length change performed (3) the velocity of displacement during the intervention. It is not dependent on the initial muscle length. Increasing the extracellular Ca-concentration considerably reduces the displacement effects. The results are tentatively explained by assuming an internal feedback loop between a variable of the contractile machinary and the preceding mechanism of activation.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2013
    Keywords: Contraction-Excitation Recoupling ; Cardiac Force Velocity Relation ; Quick Release ; Controlled Release ; Active State ; Intracellular Action Potentials ; Mechano-elektrische Rückkoppelung ; Kraft-Geschwindigkeitsrelation ; “quick release” ; kontrollierter Release ; “active state” ; intracelluläre Aktionspotentiale
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An isolierten Katzenpapillarmuskeln wurden intracelluläre Potentialmessungen bei verschiedenen Kontraktions-Bedingungen durchgeführt. Es wurde gefunden, daß die Aktionspotentialdauer (in Grenzen von etwa 20%) von der Kontraktionsform abhängig ist. Während isotonischer Verkürzung wird das Aktionspotential verlängert, bei isometrischer Spannungsentwicklung abgekürzt. Als Folge dieser Aktionspotential-Veränderungen entwickeln sich treppenartige Zu-oder Abnahmen der mechanischen Aktivität während der folgenden 5–10 Kontraktionen. Durch Anwendung einer kontrollierten Dehnung konnte die Verkürzungsgeschwindigkeit des contractilen Elements (V CE ) kleiner als bei isometrischen Bedingungen gemacht werden. Dabei wurde eine weitere Aktionspotentialverkürzung beobachtet. WurdeV CE dagegen durch Entlastungsexperimente (quick release) über die bei leicht belasteten isotonischen Kontraktionen entwickelte Verkürzungsgeschwindigkeit hinaus erhöht, so ergab sich eine weitere Zunahme der Aktionspotentialdauer. Release-Experimente, die nach der vollständigen Repolarisation durchgeführt wurden, führten zur Auslösung einer neuen Repolarisationswelle von 10–15 mV Amplitude. Zuweilen wurde hierdurch ein neues Aktionspotential ausgelöst. Die Entlastungsexperimente ermöglichten die Abschätzung der “mechanoelektrischen Latenzzeit” des beschriebenen Rückkoppelungssystems. Diese betrug weniger als 10 msec. Die beschriebenen Phänomene lassen sich vermutlich nicht auf Änderungen der membranären Oberflächengeometrie zurückführen. Andere Erklärungsmöglichkeiten werden als Arbeitshypothesen diskutiert. Es erscheint zumindest sicher, daß der Control-Parameter des beschriebenen Rückkoppelungssystems in der Kraft-Geschwindigkeits-Relation des contractilen Elementes selbst zu suchen ist. Möglicherweise bestimmt dessen Kontraktionsform die Dynamik der kontraktionswirksamen Calciumbewegungen.
    Notes: Summary Measurements of transmembrane potentials were performed under different contractile conditions on isolated cat papillary muscles. It was found that the duration of the action potential (within limits of about 20%) depends on the mode of contraction. Isotonic shortening tends to prolong, isometric tension development tends to shorten the duration of the action potential. As a result of the action potential alterations negative or positive inotropic mechanical transients are observed during 5–10 subsequent beats. The decrease in action potential duration is roughly proportional to the force development, and the increase of action potential duration is related to the shortening velocity. By applying a controlled stretch the shortening velocity of the contractile element (V CE ) was reduced below its value during purely isometric conditions. A further decrease of the action potential duration was observed. IncreasingV CE by release experiments increased the action potential duration beyond that observed under lightly loaded isotonic contractions. A quick release taking place after repolarization is complete produces a new distinct wave of depolarization (10–15 mV) which can sometimes initiate a new action potential. The quick release experiments fascilitated the estimation of the time delay of the feedback interaction which is less than 10 msecs. The possibility that passive geometrical changes of the plasma membrane is a causitive factor of the described phenomenon was experimentally excluded. Alternative explanations are discussed. It seems likely that a controlling parameter of this excitation contraction feedback system is contained in the force velocity relation of the contractile element influencing the internal Ca++-transients by its mode of contraction.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 290 (1975), S. 81-97 
    ISSN: 1432-1912
    Keywords: Verapamil ; D 600 ; Optical Isomers ; Cardiac Muscle ; Transmembrane Action Potential
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Excitability, maximum velocity of depolarization (MVD), conduction velocity, discharge rate and the duration of transmembrane action potentials as a function of frequency of stimulation were studied in isolated cardiac tissues exposed to the optical isomers of verapamil and D 600. 1. In isolated papillary muscles depression of the MVD and the conduction velocity depend on concentration (1–8 μg/ml) of (+)-verapamil and (+)-D 600. 2. (+)-Verapamil and (+)-D 600 (1–30 μg/ml) increase frequency-dependently the threshold intensity of electrical stimuli needed to elicit conducted action potentials. 3. (-)-Verapamil and (-)-D 600 are about one order of magnitude less effective than the corresponding (+)-isomers. 4. Both (+)- and (-)-isomers slightly prolong the transmembrane action potential at 90% repolarization level, particularly at low frequencies. In addition, the (-)-isomers induce a frequency-dependent depression of the plateau phase. 5. The results indicate that, at least in ventricular myocardium, the (+)-isomers of verapamil and D 600 have a quite specific inhibitory effect on the fast Na-inward current and, therefore, may contribute to some extent to the anti-dysrhythmic potency of the racemic drugs. 6. In isolated cat SA-nodes, both (+)- and (-)-isomers of verapamil and D 600 (0.2–1.0 μg/ml) reduce the discharge rate to the point of complete suppression of automaticity; different mechanisms are responsible for the effects. 7. The (-)-isomers (0.3–0.6 μg/ml) slightly reduce the slope of the slow diastolic depolarization, while causing a more effective depression of MVD and nodal conduction velocity until partial or complete nodal conduction blocks occur. 8. The (+)-isomers (1–2μg/ml) do not affect MVD or nodal conduction, but obviously shift the threshold voltage for the fast depolarization to less negative voltages. Cessation of automaticity occurs with a stable membrane potential and the ability to generate conducted action potentials by electrical stimulation persists.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Rapid Communications in Mass Spectrometry 4 (1990), S. 293-296 
    ISSN: 0951-4198
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: The matrix-assisted desorption/ionization of large biomolecules with a wavelength of 2.94 μm in the infrared is reported. A mechanically Q-switched Erbium-YAG laser with a pulse width of ca. 200 ns was used for the experiments. A large variety of matrices have been used successfully, among them all matrices found useful for ultraviolet desorption and, in addition, carboxylic acids, glycerol and urea. Desorption of molecules at this wavelength and caffeic acid as a matrix results in ions with up to 13 charges per ion.
    Additional Material: 6 Ill.
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  • 9
    ISSN: 0951-4198
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: In matrix-assisted laser desorption ionization (MALDI) a large fraction of analyte ions undergo post-source decay (PSD) during flight in the field-free drift path. By means of a modified two-stage reflectron, product ion time-of-flight spectra of medium-sized linear peptides (up to 2800 u) were recorded, containing full sequence information. Precision, accuracy and mass resolution of fragment ions were almost as good as obtained in high-energy collisionally activated dissociation (CAD) studies performed in four-sector instruments. Instrumental sensitivity was better by at least one order of magnitude. In reflectron time-of-flight mass spectrometry (RETOF-MS) the cleavage pattern of PSD products is different from that obtained by high-energy and low-energy CAD. Activation mechanisms of PSD were found to be largely determined by collisional events (ion/neutral) occurring in the acceleration field during early plume expansion. Future potentials of PSD analysis after MALDI are discussed.
    Additional Material: 6 Ill.
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  • 10
    ISSN: 0142-2421
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: The composition and the chemical states of components of Zircaloy-4 (zirconium alloy) surfaces were studied in the temperature range between room temperature and 500°C. Each sample was kept at constant temperature (25, 100, 200, 300, 400, 500°C) for up to 16 hours. The changes of composition and chemical states of the Zircaloy-4 surface during heating were monitored by x-ray photoelectron spectroscopy (XPS). Originally, the components form well-defined layers elucidated by angle-resolved x-ray photoelectron spectroscopy (ARXPS). In contrast to depth profiling using ion sputtering, ARXPS is non-destrutive. However, it is applicable for layers of up to a few nanometres thickness only.The experiments showed a decomposition of the ZrO2 coverage above 200°C accompanied by oxygen diffusion into the bulk. These processes lead to the reduction of ZrO2 to metallic zirconium on the surface at 300°C and higher temperatures. The oxygen diffusion into the bulk was indicated by AES depth profiles. The layered structure observed up to a heating temperature of 200°C could not be seen at higher temperatures. After Zr metal appears at the surface during the heating process, a reaction with the adsorbed hydrocarbons takes place, leading to the formation of zirconium carbide.Though the depth resolution of an AES depth profile does not permit identification of layers with thicknesses in the nanometre region, the temperature-dependent behaviour of oxyen is reflected by its AES profiles, showing features in accordance with the results from ARXPS, especially with respect to the fact that well-defined layers vanish above 200°C.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
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