acetylstrophanthidin and actodigin

The purpose of the present study was to examine the differences between cardiac steroids that might underlie the variations in toxic/therapeutic ratios that have been reported to occur in vitro as well as in vivo. We used Na(+)-sensitive microelectrodes to measure changes in intracellular Na+ activity (aiNa) associated with positive inotropic and toxic effects of acetylstrophanthidin (AS) and a semisynthetic agent, actodigin. Measurements of aiNa, twitch tension and transmembrane potential were made in sheep Purkinje fibers stimulated at 0.03, 1 and 2 Hz. Ca(+)+i overload toxicity was indicated by the presence of transient depolarizations (TD). The following results were obtained: 1) at a stimulation frequency of 1 Hz, aiNa was significantly higher at peak tension with AS (13.6 +/- 1.1 mM) than with actodigin (11.0 +/- 0.4 mM, P less than .01), yet TD occurred at the same aiNa (10.9 +/- 0.7 vs. 11.9 +/- 0.7 mM, respectively, N.S.); 2) at frequencies of 1 to 2 Hz, aiNa was lower when TD occurred (10.4 +/- 0.9 mM at 2 Hz) than at peak tension (12.1 +/- 0.8 mM, P less than .05) during exposure to AS, whereas aiNa was the same at peak tension (10.6 +/- 1.1 mM) and when TD occurred (10.5 +/- 1.1 mM, N.S.) during exposure to actodigin; 3) the degree of positive inotropy at a high stimulation frequency (2 Hz) was significantly greater with actodigin (about 12-fold increase in force compared to control) than with AS (about 6-fold increase in force).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Action Potentials; Animals; Cardenolides; Intracellular Fluid; Membrane Potentials; Microelectrodes; Myocardial Contraction; Purkinje Fibers; Sheep; Sodium; Strophanthidin

Changes in intracellular sodium ion activity (aiNa) produced by several cardiac glycosides were correlated with twitch tension in sheep cardiac Purkinje strands. Simultaneous measurements of aiNa and twitch tension were obtained through the use of Na-sensitive intracellular microelectrodes (ETH 227) in Purkinje preparations stimulated at a frequency of 1 Hz. All concentrations of ouabain, acetylstrophanthidin, and actodigin that were tested caused an increase in aiNa immediately before, or coincident with, a positive inotropic effect. No fall in aiNa was observed at any positive inotropic concentration of digitalis in these beating fibers. In all cases, the onset and washout of the positive inotropic effect were paralleled by the rise and fall in aiNa, respectively. No dissociation between changes in aiNa and twitch tension occurred at any concentration of any of the agents used. The relation between changes in aiNa and twitch tension was linear with 1 mM increase in aiNa producing about a 100% increase in the twitch magnitude. Propranolol did not significantly alter this relationship. The increase in aiNa with digitalis was also associated with a reduction in the maximum depolarization rate of the action potential, presumably as a consequence of a reduction in the transmembrane Na electrochemical gradient. These results indicate that the positive inotropic action of digitalis in sheep Purkinje strands is always associated with a rise in aiNa secondary to inhibition of the Na pump. This increase in aiNa could increase calcium available for contraction via the Na-Ca equilibrium exchange process. In addition, the increase in aiNa reduces Vmax, as a consequence of decreasing the electrochemical gradient for Na.

Topics: Action Potentials; Animals; Cardenolides; Digitalis Glycosides; Electrophysiology; Heart Conduction System; Ion Channels; Myocardial Contraction; Ouabain; Purkinje Fibers; Sheep; Sodium; Strophanthidin

The effects of membrane potential on digitalis-induced oscillatory afterpotentials (OAP) and aftercontractions (AC) were investigated in isolated canine false tendons and canine and feline papillary muscles. Transmembrane potential and contractions were measured simultaneously. Membrane potential was varied by current applied through an extracellular pipet. The amplitudes of OAP and AC induced by acetylstrophanthidin (0.5-1.0 X 10(-7) g/ml) or actodigin (0.5-1.0 X 10(-6) g/ml) were increased by depolarization and decreased or abolished by hyperpolarization in all tissues. Prior to the appearance of OAP and AC in preparations exposed to the drugs, depolarization caused both phenomena to appear. As in muscle, the strength of beats superimposed on the ascending limb of AC was potentiated, and the strength of beats superimposed on the relaxation phase was depotentiated. When the amplitude of AC was decreased by hyperpolarization, both potentiation and depotentiation were diminished. This effect was accompanied by a partial reversal of the changes induced by acetylstrophanthidin in the course of restitution of contractility and the configuration of the force-frequency relation.

Topics: Animals; Cardenolides; Cardiac Glycosides; Digitalis Glycosides; Dogs; Female; Heart; Male; Membrane Potentials; Myocardial Contraction; Strophanthidin