Halothane and Isoflurane Do Not Directly Interact with Cardiac Cross-bridge Function

Abstract

Background Halogenated anesthetics depress myocardial contractility by altering a number of specific mechanisms. These alterations include decreases in inward calcium current and sarcoplasmic reticulum function and reduced calcium myofilament sensitivity. However, the direct effects of volatile anesthetics on cross-bridge function have yet to be precisely determined. Methods Myosin monomers and actin filaments were isolated from fresh rat left ventricles and rabbit skeletal muscles, respectively. Halothane or isoflurane was added at concentrations equivalent to 1 and 2 minimum alveolar concentration (MAC). Motility of actin filaments over myosin was initiated by adding 2 mm adenosine triphosphate and was analyzed at 30 degrees C. Maximum actomyosin adenosine triphosphatase activity and the association constant of myosin for actin were determined from a double-reciprocal Lineweaver-Burk plot of the adenosine triphosphatase rate versus actin concentration. A known inhibitor of actomyosin function, 2,3-butanedione 2-monoxime (2 mm), was used in positive control experiments. Data are presented as mean +/- SD. Results Motility velocities driven by myosin were not significantly different between baseline and 1 and 2 MAC halothane (2.70 +/- 0.33, 2.72 +/- 0.36, and 2.70 +/- 0.40 microm/s, respectively). Similarly, motility velocities driven by myosin were not significantly different between baseline and 1 and 2 MAC isoflurane (2.73 +/- 0.33, 2.72 +/- 0.37, and 2.72 +/- 0.40 microm/s, respectively). Neither of the two halogenated anesthetics, at any concentration tested, significantly modified the maximum actomyosin adenosine triphosphatase activity or the association constant of myosin for actin as compared with baseline. 2,3-Butanedione 2-monoxime induced a drastic reduction in both motility velocity and maximum actomyosin adenosine triphosphatase activity. Conclusion These results indicate that isoflurane and halothane do not directly depress the mechanical or enzymatic properties of cross-bridges in the heart.