Related Experiment Videos
Differential influence of various calcium-modulating compounds on ouabain intoxication in isolated rat left atria
D Wilhelm1, E Scheufler, T Peters
1Janssen Research Foundation, Neuss, FRG.
Abstract:
Various calcium-modulating compounds were tested with respect to their protective action against cardiac glycoside toxicity. At the concentrations applied, control force of contraction was reduced by nifedipine and verapamil and slightly attenuated by flunarizine, R 56865, and cimetidine, while it was strongly enhanced by Bay K 8644. The positive inotropic response to ouabain (stimulation rate: 1 Hz) was impaired by nifedipine and verapamil. The increment in contractile force induced by Bay K 8644 was not enhanced by ouabain. The increase in diastolic tension during toxic conditions of ouabain (stimulation rate: 3 Hz) was attenuated by nifedipine, verapamil, bepridil, flunarizine, cimetidine, phenytoin, and R 56865 but not by diltiazem, amiodarone, and amiloride. K loss was prevented by nifedipine, verapamil, diltiazem, bepridil, flunarizine, cimetidine, phenytoin, and R 56865. The increase in cellular Na content was inhibited by R 56865 only. Ca gain was prevented by verapamil, bepridil, flunarizine, R 56865, and cimetidine but not by nifedipine, diltiazem, phenytoin, amiodarone, and amiloride. Ionic deterioration was enhanced by Bay K 8644. These results suggest that pretreatment with various calcium-modulating compounds protects against mechanical and ionic changes during ouabain intoxication induced by Na-Ca overload through different mechanisms.
Insights
Calcium-modulating drugs protect against cardiac glycoside toxicity by mitigating mechanical and ionic changes. These compounds offer varied protective mechanisms against ouabain-induced sodium-calcium overload.
Area of Science:
- Cardiology
- Pharmacology
- Cell Physiology
Background:
- Cardiac glycosides, like ouabain, induce toxicity through sodium-calcium overload.
- Calcium-modulating compounds are investigated for their potential to counteract this toxicity.
Purpose of the Study:
- To evaluate the protective effects of various calcium-modulating compounds against cardiac glycoside toxicity.
- To elucidate the mechanisms underlying the protective actions of these compounds.
Main Methods:
- Assessment of contractile force and diastolic tension in cardiac preparations.
- Measurement of intracellular potassium (K), sodium (Na), and calcium (Ca) content.
- Administration of ouabain and various calcium-modulating drugs, including nifedipine, verapamil, and others.
Main Results:
- Nifedipine and verapamil reduced contractile force and impaired ouabain's positive inotropic effect.
- Several compounds, including nifedipine, verapamil, and R 56865, attenuated increased diastolic tension and prevented potassium loss during ouabain intoxication.
- R 56865 uniquely inhibited sodium gain, while verapamil, bepridil, flunarizine, R 56865, and cimetidine prevented calcium gain.
Conclusions:
- Pretreatment with calcium-modulating compounds offers protection against the mechanical and ionic disturbances caused by ouabain intoxication.
- The protective effects are mediated through diverse mechanisms, including modulation of ion transport and cellular calcium handling.