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The influence of high-dose simvastatin and diltiazem on myocardium in rabbits: a haemodynamic study

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 int...

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Autores principales: Jasińska, Magdalena, Owczarek, Jacek, Orszulak-Michalak, Daria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Termedia Publishing House 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258750/
https://www.ncbi.nlm.nih.gov/pubmed/22312373
http://dx.doi.org/10.5114/aoms.2011.23401
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author Jasińska, Magdalena
Owczarek, Jacek
Orszulak-Michalak, Daria
author_facet Jasińska, Magdalena
Owczarek, Jacek
Orszulak-Michalak, Daria
author_sort Jasińska, Magdalena
collection PubMed
description 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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spelling pubmed-32587502012-02-06 The influence of high-dose simvastatin and diltiazem on myocardium in rabbits: a haemodynamic study Jasińska, Magdalena Owczarek, Jacek Orszulak-Michalak, Daria Arch Med Sci Basic Research 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. Termedia Publishing House 2011-06 2011-07-11 /pmc/articles/PMC3258750/ /pubmed/22312373 http://dx.doi.org/10.5114/aoms.2011.23401 Text en Copyright © 2011 Termedia & Banach http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic Research
Jasińska, Magdalena
Owczarek, Jacek
Orszulak-Michalak, Daria
The influence of high-dose simvastatin and diltiazem on myocardium in rabbits: a haemodynamic study
title The influence of high-dose simvastatin and diltiazem on myocardium in rabbits: a haemodynamic study
title_full The influence of high-dose simvastatin and diltiazem on myocardium in rabbits: a haemodynamic study
title_fullStr The influence of high-dose simvastatin and diltiazem on myocardium in rabbits: a haemodynamic study
title_full_unstemmed The influence of high-dose simvastatin and diltiazem on myocardium in rabbits: a haemodynamic study
title_short The influence of high-dose simvastatin and diltiazem on myocardium in rabbits: a haemodynamic study
title_sort influence of high-dose simvastatin and diltiazem on myocardium in rabbits: a haemodynamic study
topic Basic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258750/
https://www.ncbi.nlm.nih.gov/pubmed/22312373
http://dx.doi.org/10.5114/aoms.2011.23401
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