The differential effects of midazolam and diazepam on intracellular Ca2+ transients and contraction in adult rat ventricular myocytes.

Abstract:

UNLABELLED:We investigated the direct effects of midazolam and diazepam on cardiac excitation-contraction coupling in adult rat ventricular myocytes. Freshly isolated rat ventricular myocytes were loaded with fura-2/AM and field-stimulated at 28 degrees C. Intracellular Ca(2+) transients (340:380 ratio) and myocyte shortening (video edge detection) were simultaneously monitored in individual cells. Midazolam (3-100 micro M) caused a dose-dependent decrease in both peak intracellular Ca(2+) and cell shortening. Diazepam (30 and 100 micro M) increased myocyte shortening and peak Ca(2+) concomitant with a decrease in time to peak Ca(2+). A larger concentration of diazepam (>300 micro M) nearly abolished intracellular Ca(2+) and cell shortening. Midazolam (100 micro M) and diazepam (300 micro M) decreased the amount of Ca(2+) released from intracellular stores in response to caffeine. Diazepam (30 micro M), but not midazolam (10 micro M), caused a downward shift in the dose-response curve to extracellular Ca(2+) for shortening, with no concomitant effect on peak intracellular Ca(2+) transient. These results indicate that midazolam and diazepam have different inotropic effects on cardiac excitation-contraction coupling at the cellular level, which is mediated by altering the availability of intracellular-free Ca(2+). However, the benzodiazepines have no direct influence on excitation-contraction coupling in rat ventricular myocytes, except at very large doses. Inhibition of Ca(2+) release from caffeine-sensitive intracellular Ca(2+) stores may play some part in myocardial depression at the larger concentrations of benzodiazepines. Diazepam, but not midazolam, decreased myofilament responsiveness to Ca(2+). IMPLICATIONS:Midazolam and diazepam differentially alter the cardiac excitation-contraction coupling at the cellular level, which is mediated by altering the availability of intracellular free Ca(2+) in adult rat ventricular myocytes. In addition, diazepam, but not midazolam, decreases myofilament Ca(2+) sensitivity. However, the benzodiazepines have no direct influence on excitation-contraction coupling, except at very large doses.

journal_name

Anesth Analg

journal_title

Anesthesia and analgesia

authors

Kanaya N,Murray PA,Damron DS

doi

10.1097/00000539-200212000-00030

subject

Has Abstract

pub_date

2002-12-01 00:00:00

pages

1637-44, table of contents

issue

6

eissn

0003-2999

issn

1526-7598

journal_volume

95

pub_type

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