ABSTRACT
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)