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

Su, Judy Y. PhD; Bell, Janet G. BS
Anesthesia & Analgesia: May 1986

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.

This study was supported by grant HL 20754 and Research Career Development Award HL 01100 from the National Institutes of Health.

© 1986 International Anesthesia Research Society