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Linear dose response and quantitative attenuation by potassium of the inotropic action of acetylstrophanthidin
Abstract:
To evaluate the nature of the inotropic dose response of digitalis and to determine the effects of potassium on this response, isometrically contracting isolated supported right ventricular cat papillary muscles were studied relative to their peak tension and peak dT/dt increases to physiologic cumulative doses of acetylstrophanthidin (ACS) in different extracellular potassium concentrations in the muscle bath. The inotropic dose response to ACS was observed to be linear in cumulative glycoside concentrations ranging from 0.40 to 4.23 X 10(-7) M ACS in 3.5 mM K+ medium and from 1.22 to 7.47 X 10(-7) M ACS in 7.0 mM K+ medium. The influence of potassium alterations in the muscle bath from the low to the high K+ concentrations prior to ACS resulted in marked attenuation of the positive inotropic property of ACS. From these data, it is concluded that the dose inotropic response of digitalis is linear, with small doses producing proportionally the same effects as larger doses, and that extracellular potassium markedly influences this linear dose response such that higher K+ concentrations considerably attenuate the positive inotropic response of digitalis.
Insights
Digitalis exhibits a linear inotropic dose response, meaning smaller doses yield proportional effects. However, elevated extracellular potassium significantly attenuates this positive inotropic effect, impacting digitalis efficacy.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
Background:
- Digitalis glycosides are crucial for treating heart failure.
- Understanding their dose-response relationship and factors influencing it is vital for clinical application.
Purpose of the Study:
- To investigate the linear inotropic dose-response of digitalis (acetylstrophanthidin).
- To determine the impact of varying extracellular potassium concentrations on this digitalis response.
Main Methods:
- Isolated cat right ventricular papillary muscles were used for isometric contractions.
- Muscles were exposed to cumulative doses of acetylstrophanthidin (ACS) in different potassium (K+) concentrations (3.5 mM and 7.0 mM).
- Inotropic effects were measured by increases in peak tension and peak dT/dt.
Main Results:
- The inotropic dose response to ACS was linear within specific concentration ranges in both 3.5 mM K+ and 7.0 mM K+ media.
- Increasing extracellular potassium from 3.5 mM to 7.0 mM markedly attenuated the positive inotropic effects of ACS.
- Higher potassium concentrations reduced the overall positive inotropic response to digitalis.
Conclusions:
- Digitalis demonstrates a linear inotropic dose-response relationship.
- Extracellular potassium concentration significantly modulates the positive inotropic effects of digitalis.
- Higher extracellular potassium levels attenuate the efficacy of digitalis, suggesting a critical role for electrolyte balance in digitalis therapy.