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ANESTHETIC PHARMACOLOGY

Modulation of Myofilament Ca²⁺ Sensitivity by - and -Opioid Agonists in Intact Guinea Pig Hearts

Yuri Nakae, MD PhD^*, Satoshi Fujita, MD PhD, and Akiyoshi Namiki, MD PhD^*

*Department of Anesthesiology, Sapporo Medical University School of Medicine; and Departments of Anesthesiology and Critical Care Medicine, Asahikawa Medical College, Japan

Address correspondence and reprint requests to Yuri Nakae, MD, PhD, Department of Anesthesiology, Sapporo Medical University School of Medicine, West-16, South-1, Chuo-ku, Sapporo 060-8543, Japan. Address e-mail to yurinaka{at}mac.com

We investigated whether - and -opioid agonists alter myocardial function, intracellular Ca²⁺ concentration ([Ca²⁺]_i), and myofilament Ca²⁺ sensitivity in intact guinea pig beating hearts and whether these effects are mediated by an opioid receptor. Intact guinea pig hearts were perfused with modified Krebs Ringer solution containing - (TAN-67) and - (ICI-199441) opioid agonists in the absence and presence of - (BNTX) and - (nor-BNI) opioid antagonists, respectively, while functional variables and [Ca²⁺]_i were recorded. TAN-67 (1 µM) and ICI-199441 (1 µM) decreased heart rate (P < 0.05). TAN-67 (1 µM) and ICI-199441 (1 µM) decreased available [Ca²⁺]_i without changing developed left ventricular pressure (LVP) (P < 0.05). TAN-67 (1 µM) and ICI-199441 (1 µM) also caused a leftward shift in the curve of developed LVP as a function of available [Ca²⁺]_i (P < 0.05). ICI-199441 (1 µM) produced a steeper slope in the relation curve compared with baseline (P < 0.05). BNTX (1 µM) and nor-BNI (1 µM) blocked the effects of TAN-67 and ICI-199441, respectively. - and -opioid agonists enhance myofilament Ca²⁺ sensitivity despite decreasing available [Ca²⁺]_i in intact isolated guinea pig hearts, and these effects are mediated by - and -opioid receptor stimulation.

IMPLICATIONS: Our results indicate that - and -opioid agonists enhance myofilament Ca²⁺ sensitivity despite decreasing available intracellular Ca²⁺ concentrations in intact isolated guinea pig beating hearts, and these effects are mediated by - and -opioid receptor stimulation.

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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