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Anesth Analg 1987; 66:711-718
© 1987 International Anesthesia Research Society
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Pharmacologic Basis of Responses to Midazolam in the Isolated, Cross-Perfused, Canine Right Atrium

Kimiaki Saegusa, MD, Yasuyuki Furukawa, MD, Yasuhiro Ogiwara, MD, Masayoshi Takeda, MD, and Shigetoshi Chiba, MD

Received from the Department of Pharmacology and the Third Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.

Abstract

The effects of midazolam on atrial rate and contractile force in the isolated canine atrium perfused with donor blood were investigated. When midazolam in a dose range of 100–1000 µg was injected directly into the sinus node artery of the isolated atrium, biphasic (negative followed by positive) chronotropic and triphasic (positive, negative followed by positive) inotropic effects were induced. After propranolol or imipramine, the positive chronotropic and the secondary positive inotropic effects were significantly suppressed, but the initial positive inotropic effect was not affected. Tetro-dotoxin, atropine, or R05–4864, a selective ligand for peripheral benzodiazepine binding sites, did not modify mid-azolam-induced effects. When midazolam in a dose of 0.1–1 mg/kg was administered intravenously to the donor dog, monophasic negative chronotropic and inotropic effects in the isolated atrium were observed but were not as prominent. We conclude that midazolam has direct cardiac inhibitory properties including catecholamine release due to a tyra-mine-like action.

Key Words: HEART—rate, contractility • SYMPATHETIC NERVOUS SYSTEM—catecholamines • HYPNOTICS, BENZODIAZEPINES—midazolam




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N. Kanaya, P. A. Murray, and D. S. Damron
The Differential Effects of Midazolam and Diazepam on Intracellular Ca2+ Transients and Contraction in Adult Rat Ventricular Myocytes
Anesth. Analg., December 1, 2002; 95(6): 1637 - 1644.
[Abstract] [Full Text] [PDF]


Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 1987 by the International Anesthesia Research Society.