Key result
Diltiazem significantly increased the cardiac output index when given simultaneously with simvastatin in rabbits during dopamine infusion, suggesting improved cardiac efficiency.
Why the study?
Does simvastatin co-administered with diltiazem affect haemodynamic parameters after dopamine infusion in rabbits?
Does simvastatin co-administered with diltiazem affect haemodynamic parameters after dopamine infusion in rabbits?
Co-administration of simvastatin and diltiazem in a rabbit model improved cardiac efficiency (increased cardiac output index) during dopamine infusion compared to simvastatin alone.
INTRODUCTION: Simvastatin and diltiazem are often prescribed together for the treatment of hypercholesterolaemia in patients with hypertension and/or angina pectoris. However, diltiazem, a CYP3A inhibitor, is a well-recognized risk factor of skeletal muscle myopathy. It is not known whether such interaction also affects myocardial efficiency causing haemodynamic changes. The aim of the experiment was to establish the impact of simvastatin co-administered with diltiazem on the haemodynamic parameters after continuous infusion of dopamine. MATERIAL AND METHODS: The experiments were performed on 28 New Zealand white rabbits. The animals were divided into four groups receiving: 0.2% MC - methylcellulose (control group); diltiazem; simvastatin; simvastatin + diltiazem, for 14 days (po). The following haemodynamic parameters were estimated: cardiac output index (CI), heart rate (HR), systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP) and total peripheral resistance index (TPRI). The registration of haemodynamic parameters was performed by the Doppler method and during the experiments the animals were anaesthetized with α-chloralose (75 mg/kg bw) and urethane (500 mg/kg bw). RESULTS: Dopamine did not cause a statistically significant increase in CI in rabbits receiving simvastatin alone. Diltiazem significantly increased CI if given simultaneously with simvastatin, which might suggest the improvement of cardiac efficiency resulting from such interaction. CONCLUSIONS: The possibility of another mechanism of drug-drug interaction than the one based on CYP3A inhibition, and its impact on cardiac or skeletal muscle, might be considered.
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Jasińska-Stroschein et al. (2011) studied Healthy (animal model) (n=28). Simvastatin and diltiazem vs. 0.2% methylcellulose (control), diltiazem alone, simvastatin alone was evaluated on Cardiac output index (CI) during dopamine infusion (p=<0.05). Diltiazem significantly increased the cardiac output index when given simultaneously with simvastatin in rabbits during dopamine infusion, suggesting improved cardiac efficiency.
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