Electrophysiological studies of some semisynthetic cardiac glycoside derivatives in isolated papillary muscle of the guinea‐pig

Abstract

1 The effects of digitoxin, 3a-methyl-digitoxigenin-3p-monoglucoside (3a-MDM), 3a-methyldigitoxigenin (3a-MD), proscillaridin, 4, 5-methylene-procillaridin (4, 5-MP), and 3p-hydroxy-4, 5-methylene-A, B-trans-scillarenin (3p-HMTS) on force of contraction and on the transmembrane action potentials were examined in isolated papillary muscles of guinea-pigs. 2 All derivatives exhibited the typical cardiac glycoside effects: i.e. they increased the force of contraction and shortened the action potential duration at 20% (plateau phase) and 90% of repolarization. With digitoxin, 3P-HMTS and 4, 5-MP a transient prolongation in action potential duration was observed at the lower concentrations. The action potential amplitude and the resting membrane potential were reduced consistently only with the higher concentrations used.3 The onset of the positive inotropic effects of 3a-MDM, 3x-MD and 3P-HMTS was more rapid than that of digitoxin and proscillaridin. The increment in contractile force reached a maximum well before the full shortening effect on the action potential duration had developed. The shortening of the action potential is thought to be responsible for the biphasic nature of the positive inotropic effect. 4 With 3a-MD and 3a-MDM even toxic effects, e.g. increase in baseline tension, were completely reversible after washing in drug-free solution. 5 The dose-response curves for the positive inotropism can only be compared reliably once the equilibrium of drug action has been established. This steady state is probably reflected by the development of the full shortening in action potential duration.

Acrihellin

“…Marked effects were observed during phases 2 and 3 of the action potential, with a loss of plateau and a shortening of the action-potential duration (APD). The shortening of APD at low levels of the drugs is consistent with the findings with many other cardiac steroids (34,3535). At higher concentrations M), the APD at 90% repolarization (APD,,) increased slightly, but the loss of plateau became more pronounced due to the reduction of the slow inward current (61).…”

Sind Biophotonen Wirkmediator homöopathischer Arzneien?

“…Inspiriert wurde der Versuchsaufbau durch einen Versuch in meiner vorklinischen Ausbildung 1985 an der Freien Universität Berlin. Als pharmakologischen Vergleichsversuch verweise ich auf den Versuch der Universität Kiel von 1983 [4].…”