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Intracellular Mechanism of Action of Isoflurane and Halothane on Striated Muscle of the Rabbit

Received from the Department of Anesthesiology, University of Washington School of Medicine, Seattle, Washington.

Abstract

Studies were conducted on the effects of isoflurane and halothane on intracellular mechanisms of striated muscle contraction: Ca²⁺ activation of the contractile proteins and Ca²⁺ uptake and release from the sarcoplasmic reticulum. Functionally skinned muscle fibers (sarcolemma disrupted by homogenization) from isolated papillary muscle (PM), soleus (SL) (slow-twitch skeletal muscle), and adductor magnus (AM) (fast-twitch skeletal muscle) of rabbits were mounted on a photodiode tension transducer. They were immersed in control solution (saturated with N₂), then in test solution (saturated with anesthetic–N₂ mixture), and in control solution again. The following two studies were carried out: 1) in the study of Ca²⁺-activated tension development of the contractile proteins, free Ca²⁺ concentration in the bathing solution was controlled by the use of a high EGTA (7 mM), and 2) in the study of Ca²⁺ uptake and release from the sarcoplasmic reticulum (SR), Ca²⁺ was loaded into the SR and released with caffeine and the resulting tension transients were measured. Isoflurane (1–4%) decreased (6–9%) the maximal Ca²⁺-activated tension development in PM and SL but more in PM than in SL. In AM, however, isoflurane and halothane (1–3%) produced no change. Isoflurane decreased submaximal Ca²⁺ -activated tension development in PM, but effected no change in it in SL. Isoflurane and halothane increased the tension development in AM to the extent of producing a shift to the left in the pCa-tension curves of 0.1 pCa unit. Isoflurane decreased by 16% Ca²⁺ uptake by the SR in PM at 3% concentration, increased uptake 110–143% in SL at 1–3%, and increased by 72–121% and 15–73% Ca²⁺ release from the SR in SL and AM, respectively. With submaximal caffeine concentration at 2 mM, isoflurane (4% only) increased by 21% Ca²⁺ release from the sarcoplasmic reticulum in PM. Halothane (1–3%) decreased by 19–37% Co²⁺ uptake and increased by 38–75% Ca²⁺ release from the SR in skinned fibers of AM. We conclude that isoflurane and halothane have similar intracellular mechanisms of action in striated muscle. Isoflurane-induced decreases in submaximal and maximal Ca²⁺-activated tension development and in Ca²⁺ uptake by the sarcoplasmic reticulum in PM could partially contribute to decreased myocardial contractility. The increases in Ca²⁺ release from the SR produced by isoflurane and halothane in SL and AM could contribute to increased muscle contraction.

Key Words: ANESTHETICS, VOLATILE—halothane, isoflurane • MUSCLE, SKELETAL—contractility • IONS—calcium

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				B. Bouhemad, O. Langeron, G. Orliaguet, P. Coriat, and B. Riou Effects of halothane and isoflurane on the contraction, relaxation and energetics of rat diaphragmatic muscle Br. J. Anaesth., September 1, 2002; 89(3): 479 - 485. [Abstract] [Full Text] [PDF]

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