Clofibrate, calcium and cardiac muscle

Area of Science:

• Cardiology
• Pharmacology
• Molecular Biology

Background:

• Clofibrate is an anti-hyperlipidemic agent.
• Cardiac dysfunction and arrhythmias are potential side effects of clofibrate.

Purpose of the Study:

• To investigate the effects of clofibrate on cardiac muscle contractility and calcium handling.
• To elucidate the mechanisms underlying clofibrate-induced cardiac effects.

Main Methods:

• Isolated perfused rabbit heart Langendorff preparations.
• Electrically stimulated rat and guinea-pig atria.
• Varying calcium concentrations and stimulation frequencies.
• Assessment of sarcoplasmic reticulum and mitochondrial calcium uptake.

Main Results:

• Clofibrate induced negative inotropic effects and arrhythmias in rabbit hearts.
• In rat atria, clofibrate's negative inotropic effects were modulated by calcium concentration and stimulation frequency.
• The drug inhibited calcium uptake by cardiac sarcoplasmic reticulum and mitochondria, but not calcium release.
• Sensitivity to clofibrate varied under different electrophysiological conditions.

Conclusions:

• Clofibrate exerts multiple effects on cardiac calcium handling.
• These effects on calcium ions likely contribute to clofibrate's negative inotropic actions and potential for arrhythmias.
• Further research is needed to fully understand the clinical implications of these findings.