Effects of different cardiac steroids on intracellular sodium, inotropy and toxicity in sheep Purkinje fibers.
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)
Wasserstrom
J A
JA
Reingold ECG Center (Section of Cardiology, Department of Medicine), Northwestern University Medical School, Chicago, Illinois.
Farkas
D E
DE
Norell
M A
MA
Vereault
D V
DV
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002298:Cardenolides / Q000494:pharmacology* / Q000633:toxicity; D007424:Intracellular Fluid / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008839:Microelectrodes; D009200:Myocardial Contraction / Q000187:drug effects*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D012756:Sheep; D012964:Sodium / Q000378:metabolism / Q000502:physiology; D013327:Strophanthidin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity
D002298:Cardenolides; D013327:Strophanthidin; C006277:actodigin; D012964:Sodium; C004681:acetylstrophanthidin