Related Experiment Videos
Calcium-dependent toxic effects of digoxin in isolated myocardial preparations
Abstract:
On isolated guinea-pig papillary muscles as well as on electrically driven atria digoxin was infused into the bath fluid until cardiac arrest occurred. The concentration of digoxin which caused standstill is defined as the toxic one. The toxicity was determined under various Ca2+-concentrations. On the papillary muscle the increase of extracellular Ca2+ from 0.9 to 7.2 mM increased the toxicity of digoxin, i.e. significantly diminished its toxic concentrations. Likewise, on electrically driven atria an increase of Ca2+ from 0.45 to 7.2 mM increased the toxicity of digoxin. These results demonstrate that with regard to the toxicity Ca2+ and digoxin act synergistically.
Insights
Calcium and digoxin toxicity show synergy. Increasing extracellular calcium concentrations significantly reduced the toxic levels of digoxin, enhancing its cardiotoxicity in guinea-pig heart muscle preparations.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
Background:
- Digoxin is a cardiac glycoside used to treat heart failure and arrhythmias.
- Its therapeutic index is narrow, and toxicity can lead to serious cardiac events.
- Extracellular calcium concentration is a critical factor in cardiac function and drug response.
Purpose of the Study:
- To investigate the effect of varying extracellular calcium concentrations on digoxin toxicity.
- To determine if calcium and digoxin interact synergistically in causing cardiac toxicity.
Main Methods:
- Isolated guinea-pig papillary muscles and electrically driven atria were used.
- Digoxin was infused until cardiac arrest occurred, defining the toxic concentration.
- Experiments were conducted across a range of extracellular calcium concentrations (0.45–7.2 mM).
Main Results:
- In papillary muscles, increasing extracellular calcium from 0.9 to 7.2 mM significantly decreased the toxic concentration of digoxin.
- In electrically driven atria, increasing calcium from 0.45 to 7.2 mM also enhanced digoxin's toxicity.
- These findings indicate a synergistic interaction between calcium and digoxin toxicity.
Conclusions:
- Extracellular calcium concentration modulates digoxin toxicity.
- Calcium and digoxin exhibit a synergistic relationship in inducing cardiac toxicity.
- Clinical management of digoxin therapy may need to consider patient calcium levels.