Selective updates on mechanisms of action of positive inotropic agents

Grupp, Günter

doi:10.1007/bf00223475

Cited by 20 publications

(2 citation statements)

References 88 publications

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“…Amrinone has been shown to be a specific phosphodiesterase (PDE) I11 inhibitor (Endoh et ul. 1982, Hayes et al 1984, thus causing increased levels of CAMP in the heart. This will lead to increased amounts of activated CAMPdepcndcnt protein kinases, which in turn govern phosphorylation of various intracellular proteins.…”

Section: Decline Of Post-extrasystolic Potentiationmentioning

confidence: 99%

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Inotropic mechanisms of amrinone in papillary muscles from guinea‐pig hearts

Mörner

Wohlfart

1990

Acta Physiologica Scandinavica

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Isometric force and action potentials were recorded in papillary muscles from guinea-pigs (temperature 33 degrees C, stimulation frequency 0.5 Hz). Amrinone (1 mM) increased peak twitch force (to 220% of control, n = 12) and rate of rise of force (to 221% of control, n = 12), while time from peak to half-relaxation was markedly reduced (to 70% of control). The time to peak force was not significantly changed. Action potential at 50% repolarization was shortened (93.3% of control, n = 8), whereas plateau voltage became more positive. Peak twitch force in response to a test stimulus after a varied interval, i.e. mechanical restitution, was increased at all intervals by the drug. However, the time to full mechanical restitution (1.5 s) was not affected. Forces in response to the test interval preceding the previous contraction (post-extrasystolic potentiation) were analysed. Maximum potentiation was 16.0 mN mm-2 (2.7 +/- 0.4%) before and 22.6 mN mm-2 (1.7 +/- 0.1%) after addition of the drug, i.e., the relative potentiation was diminished in the presence of the drug. The test interval for optimum potentiation was shortened from 370 to 320 ms (P less than 0.05, n = 12) in 1 mM amrinone. During decay of post-extrasystolic potentiation peak force of the post-potentiated contraction was linearly related to force of the potentiated contraction. The slope of this line (which is believed to monitor recirculation of activator calcium) was increased by amrinone from 0.37 to 0.50 (P less than 0.01, n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Decline Of Post-extrasystolic Potentiationmentioning

confidence: 99%

“…Both internal factors like the interval between beats (Koch-Weser & Blinks 1963, Edman & Johannsson 1976, Wohlfart & Noble 1982) and external influences, e.g. inotropic substances (Grupp 1987), can modify force production. I n this study programmed stimulation was used as a tool to vary the contractile strength.…”

mentioning

confidence: 99%

Inotropic mechanisms of amrinone in papillary muscles from guinea‐pig hearts

Mörner

Wohlfart

1990

Acta Physiologica Scandinavica

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Digitalisforschung in Berlin‐Buch – Rückblick und Ausblick

et al. 1995

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Der Arzt William Withering führte 1785 mit seinem Buch „An Account of the Foxglove and some of its Medical Uses”︁ Präparate aus Digitalisblättern in die Therapie der Wassersucht (des Herzversagens) ein und erklärte: „The following remarks consist partially of matter of fact, and partially of opinion. The former will be permanent; the latter must vary with the detection of error, or the improvement of knowledge. I hazard them with diffidence, and hope they will be examined with candour.”︁ Diese Bemerkungen sind hier vom Seniorautor angeführt, da er die Schwierigkeit sieht, einen ausgewogenen Bericht über sein lebenslanges Forschungsprojekt zur Digitalis‐Weiterentwicklung zu bieten. Seine Entscheidung, sich der Digitalisforschung zu widmen, entstand am Krankenbett, an dem er als Arzt die furchtbaren Endstadien des Herzversagens erlebte, in denen für die Kranken keine wirkliche Hilfe mehr möglich ist. Unglücklicherweise paßte dieses Vorhaben nicht in das vom Wissenschaftsministerium der DDR dekretierte Forschungsprogramm, so daß er das Digitalisprojekt zugunsten von Biomembran‐Untersuchungen einstellen sollte. Glücklicherweise entging er dem Verdikt durch Etikettierung der digitalisartig wirkenden Steroide als chemische Sonden für die Zellmembran‐lokalisierte Na+/K+ ‐transportierende ATPase, die er gerade als den Digitalisrezeptor erkannt hatte. Über die Arbeit der Autoren wird hier erstmals im Zusammenhang berichtet. Ziel des Überblicks ist, die Forschung für die Lösung einer großen Aufgabe zu fördern: die Entwicklung von Steroidwirkstoffen zur Verhinderung und Heilung der Herzinsuffizienz.

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Digitalis Research in Berlin–Buch—Retrospective and Perspective Views

Repke¹,

Megges²,

Weiland³

et al. 1995

Angew. Chem. Int. Ed. Engl.

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“The following remarks consist partially of matter of fact, and partially of opinion. The former will be permanent; the latter must vary with the detection of error, or the improvement of knowledge. I hazard them with diffidence, and hope they will be examined with candour.” These declarations, which stem from the famous book “An Account of the Foxglove and some of its Medical Uses” by physician William Withering in 1785 in which he introduced preparations from digitalis leaves in the therapy of dropsy (cardiac failure), are cited here by the senior author because of his awareness of the difficulties in presenting a balanced report on his life‐long research project on the further development of digitalis. His decision to devote himself to digitalis research originated at the bedside, when as a physician he experienced the grim final stages of cardiac failure in which no real help for the patients is possible. Unfortunately, his research project did not fit into the research program decreed by the Ministry of Science of the German Democratic Republic, so that he was ordered to stop the digitalis project in favor of biomembrane studies. Fortunately, he got round the ban simply by labeling the digitalis‐like acting steroids as probes for the cell membrane‐located Na+/K+‐transporting ATPase which he had just recognized as the digitalis target (receptor) enzyme. These and other ventures by the authors are collated here for the first time. The aim of this review is to foster straightforward research for solving a major challenge: the development of steroidal drugs for the prevention and cure of cardiac failure.

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Selective updates on mechanisms of action of positive inotropic agents

Cited by 20 publications

References 88 publications

Inotropic mechanisms of amrinone in papillary muscles from guinea‐pig hearts

Inotropic mechanisms of amrinone in papillary muscles from guinea‐pig hearts

Digitalisforschung in Berlin‐Buch – Rückblick und Ausblick

Digitalis Research in Berlin–Buch—Retrospective and Perspective Views

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