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Mechanism of the negative inotropic effect of midazolam and diazepam in cultured foetal mouse cardiac myocytes

Published online by Cambridge University Press:  16 August 2006

A. Nonaka ,
S. Kashimoto ,
M. Imamura ,
A. Furuya  and
T. Kumazawa
A. Nonaka
Affiliation:
Department of Anaesthesiology, Yamanashi Medical University, Shimokato 1110, Tamaho, Nakakoma, Yamanashi, 409-38, Japan
S. Kashimoto
Affiliation:
Department of Anaesthesiology, Yamanashi Medical University, Shimokato 1110, Tamaho, Nakakoma, Yamanashi, 409-38, Japan
M. Imamura
Affiliation:
Department of Anaesthesiology, Yamanashi Medical University, Shimokato 1110, Tamaho, Nakakoma, Yamanashi, 409-38, Japan
A. Furuya
Affiliation:
Department of Anaesthesiology, Yamanashi Medical University, Shimokato 1110, Tamaho, Nakakoma, Yamanashi, 409-38, Japan
T. Kumazawa
Affiliation:
Department of Anaesthesiology, Yamanashi Medical University, Shimokato 1110, Tamaho, Nakakoma, Yamanashi, 409-38, Japan
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Abstract

We have investigated the effects of midazolam and diazepam on intracellular calcium (Ca2+) handling in foetal mouse ventricular myocytes using the Ca2+-sensitive fluorescent indicator, indo-1. We also investigated separately whether flumazenil or the L-type Ca2+channel agonist, Bay K8644, antagonized these myocardial depressive effects. Midazolam and diazepam decreased the Ca2+transient and beating rate in a concentration-dependent manner, and these decreases were prevented by Bay K8644. Flumazenil did not antagonize the myocardial depressive effects. In myocytes whose sarcoplasmic reticulum was inhibited by ryanodine, midazolam and diazepam had the same potent cardiodepressive effects. Midazolam and diazepam are direct cardiac depressants, which decrease the Ca2+transient and beating rate, and the L-type Ca2+channel is important in the negative inotropism and chronotropism caused by these drugs.

Keywords

benzodiazepinesdiazepammidazolamheartmyocyteionscalciummethodscalcium sensitive fluorescent dyeindo-1
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 14 , Issue 5 , September 1997 , pp. 481 - 487
Copyright
1997 European Society of Anaesthesiology

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