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[Pharmacologic effects of mansonine on arrhythmias induced in isolated rat heart]
E E Ehile1, A Mensah-Nyagan, G F Guédé
1Laboratoire de Physiologie Animale et de Psychophysiologie, Faculté des Sciences et Techniques, Université Nationale de Côte d'Ivoire, Abidjan, Côte d'Ivoire.
Abstract:
The effect of 3 x 10(-13) M Mansonine (MSN) was observed on arrythmias induced on isolated rat heart, perfused with either hypopotassic solution, atropine solution, or MacEwen physiological saline at 18 degrees C. Generally the reversal of induced arrythmias was complete with the hypopotassic solution, and partial with the MacEwen solution at 18 degrees C. On the other hand, when atropine and MSN were combined, their effects induced heart arrest, probably due to an intracellular calcium accumulation. In this case, the heart recovery occurred by preventing the calcium influx, either through EDTA chelation, or blockade of calcium channels. It was concluded that MSN probably acts like most cardiac glycosides, by blocking the Na(+)-K+ ATPase. This may activate a calcium influx, which causes the subsequent positive inotropic effect, as well as a negative chronotropic effect due to an increase of the membrane activation set point.
Insights
Mansonine (MSN) reversed induced heart arrhythmias in rat models. Combined with atropine, it caused heart arrest, likely via calcium accumulation, suggesting a cardiac glycoside-like mechanism.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Cardiac Electrophysiology
Context:
- Investigating the effects of novel compounds on cardiac function is crucial for understanding potential therapeutic applications.
- Arrhythmias pose a significant health risk, necessitating research into agents that can modulate cardiac rhythm.
- The Na(+)-K+ ATPase is a key regulator of cardiac cell function and a target for various drugs.
Purpose:
- To elucidate the electrophysiological effects of Mansonine (MSN) on isolated rat hearts.
- To determine the mechanism of action of MSN, particularly its interaction with ion channels and intracellular calcium.
- To assess the potential of MSN in managing experimentally induced cardiac arrhythmias.
Summary:
- Mansonine (MSN) at 3 x 10(-13) M demonstrated varying degrees of arrhythmia reversal in isolated rat hearts under different perfusion conditions (hypopotassic, atropine, MacEwen saline at 18°C).
- Co-administration of atropine and MSN resulted in cardiac arrest, attributed to intracellular calcium accumulation, which was reversible by blocking calcium influx (EDTA chelation, calcium channel blockade).
- The study concludes that MSN likely functions similarly to cardiac glycosides by inhibiting Na(+)-K+ ATPase, leading to calcium influx, a positive inotropic effect, and a negative chronotropic effect.
Impact:
- Provides insights into the potential anti-arrhythmic and inotropic properties of Mansonine.
- Suggests a novel mechanism involving Na(+)-K+ ATPase inhibition and calcium modulation for MSN.
- Highlights the importance of calcium homeostasis in mediating the cardiac effects of MSN and its potential interactions.