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

Abstract

SU JY, BELL JG. Intracellular mechanism of action of isoflurane and halothane on striated muscle of the rabbit. Anesth Analg 1986;65:457-62.Studies were conducted on the effects of isoflurane and halothane on intracellular mechanisms of striated muscle contraction: Caz+ activation of the contractile proteins and Ca2+ uptake and release from the sarcoplasmic reticulum. Functionally skinned muscle fibers (sarcolemma disrupted by homogenization) from isolated papilla y muscle (PM), soleus (SL) (slow-twitch skeletal muscle), and adductor magnus ( A M ) (fast-twitch skeletal muscle) of rabbits were mounted on a photodiode tension transducer. They were immersed in control solution (saturated with NJ, then in test solution (saturated with anesthetic-N, mixture), and in control solution again. The following two studies were carried out: I) 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 21 in the study of Ca" uptake and release from the sarcoplasmic reticulum (SR), Ca2+ was loaded into the SR and released with cafjeine and the resulting tension transients were measured. lsoflurane (1-4%) decreased (6-9%) the maximal Ca2 + -activated tension development in PM and SL but more in PM than in SL. In AM, howeuer, 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. lsoflurane and halothane increased the tension development in AM to the extent of producing a shift to the left in the pCa-tension curves of 50.1 pCa unit. lsoflurane decreased by 16% Ca2+ uptake by the SR in PM at 3% concentration, increased uptake 110-143% in S L at 1-3%, and increased by 72-121 % and 15-73% Ca2+ release from the SR in S L and A M , respectively. With submaximal caffeine concentration at 2 mM, isoflurane (4% only) increased by 21% Ca" release from the sarcoplasmic reticulum in PM. Halothane (1-3%) decreased by 19-37% Ca2 + uptake and increased by 38-75% Ca2+ release from the SR in skinned fibers of AM. We conclude that isoflurane and halothane have similar infracellular mechanisms of action in striated muscle. lsoflurane-induced decreases in submaxima1 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 S L and AM could contribute to increased muscle contraction.

Reversal of Isoflurane-Induced Depression of Myocardial Contraction by Nitroxyl via Myofilament Sensitization to Ca2+

“…Ca 2ϩ responsiveness to inhalational anesthetics decreased (Herland et al, 1993), whereas others have shown no change or increased myofilament Ca 2ϩ responsiveness (Su and Kerrick, 1980;Su and Bell, 1986;Murat et al, 1988). Taken together, these studies suggest that, at least in part, the myofilament desensitization may reflect changes in the soluble cytoplasmic factors.…”

“…This clearly hints at the possibility that ISO directly decreases myofilament Ca 2ϩ responsiveness. Nonetheless, early studies that used skinned cardiac muscle preparations yielded variable results; some failed to show any effect of ISO at low concentrations (i.e., clinically relevant doses: 1-3%) (Su and Kerrick, 1980;Su and Bell, 1986), and others showed either increased or decreased myofilament Ca 2ϩ sensitivity Herland et al, 1993). The contention was that the presence of a cellular membrane system could influence the modulation of cardiac inotropy by inhalational agents (Herland et al, 1993).…”

Anesthesia of the critically ill equine patient

“…An additional consideration is the effect of inhalant agents on calcium flux into cardiac cells, which is thought to mediate their myocardial depressant effects [92,93]. Grubb et al [94] reported improvement in myocardial function in halothane-and isoflurane-anesthetized horses with calcium gluconate infusion.…”

Mechanisms of force inhibition by halothane and isoflurane in intact rat cardiac muscle

“…In addition to reducing the amount of Ca¥ released into the cytosol, the volatile anaesthetics have also been reported to alter the response of the contractile system to activator Ca¥. Various studies using chemically (Murat, Ventura-Clapier & Vassort, 1988) or mechanically (Su & Kerrick, 1978;Su & Bell, 1986) skinned cardiac muscle preparations have consistently shown that halothane and isoflurane decrease maximal Ca¥-activated force and the Ca¥ sensitivity of the contractile system. In contrast, in an elaborate study employing a range of chemical-and mechanical-skinning techniques, Herland, Julian & Stephenson (1993) found that the magnitude and, even, direction of the effect of volatile anaesthetics on maximal Ca¥-activated force and Ca¥ sensitivity was dependent on the particular technique employed.…”