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CARDIOVASCULAR ANESTHESIA

Morphine Enhances Myofilament Ca²⁺ Sensitivity in Intact Guinea Pig Beating Hearts

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

*Department of Anesthesiology, Sapporo Medical University School of Medicine; and Department of Anesthesia, Hokkaido Keiaikai Minami 1-jyo Hospital, Sapporo, Japan

Address correspondence and reprint requests to Yuri Nakae, MD, PhD, Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226-0509. Address e-mail to ynakae{at}mcw.edu

We investigated whether morphine alters intracellular Ca²⁺ concentration ([Ca²⁺]_i), left ventricular pressure (LVP), and myofilament Ca²⁺ sensitivity under physiologic conditions in intact guinea pig beating hearts and whether ₁, ₂, and opioid stimulations are related to the direct cardiac effects of morphine. Transmural LV phasic [Ca²⁺]_i was measured from fluorescence signals at 385 nm and 456 nm. The Ca²⁺ transients during each contraction were defined as available [Ca²⁺]_i. The hearts were perfused with modified Krebs-Ringer solution containing morphine in the absence and presence of ₁ (BNTX), ₂ (NTB), and (nor-BNI) antagonists, while developed LVP and available [Ca²⁺]_i were recorded. Morphine (1 µM) decreased available [Ca²⁺]_i by 44 ± 12 nM without decreasing developed LVP at 2.5 mM of [CaCl₂]_e (P < 0.05). Morphine (1 µM) caused a leftward shift in the curve of developed LVP as a function of available [Ca²⁺]_i (P < 0.05). BNTX (1 µM), but not nor-BNI (1 µM) or NTB (0.1 µM) blocked morphine (1 µM) effects to decrease available [Ca²⁺]_i. Morphine decreases available [Ca²⁺]_i but not LVP, and it enhances myofilament Ca²⁺ sensitivity under physiologic conditions at clinical concentrations in intact isolated beating guinea pig hearts. The ₁ opioid stimulation modifies the effects of morphine on Ca²⁺ transients and myofilament Ca²⁺ sensitivity.

Implications: Morphine modifies myofilament Ca²⁺ sensitivity and Ca²⁺ transients in guinea pig hearts at concentrations that are clinically relevant.

This article has been cited by other articles:

				Y. Nakae, S. Fujita, and A. Namiki Modulation of Myofilament Ca2+ Sensitivity by {delta}- and {kappa}-Opioid Agonists in Intact Guinea Pig Hearts Anesth. Analg., March 1, 2003; 96(3): 733 - 739. [Abstract] [Full Text] [PDF]