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Anesth Analg 2007;104:332-337
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000252432.51717.9f

ANESTHETIC PHARMACOLOGY

Halothane, Isoflurane, and Sevoflurane Increase the Kinetics of Ca2+-Induced Conformational Change of Recombinant Human Cardiac Troponin C

Dirk Breukelmann, MD*, and Philippe R. Housmans, MD, PhD{dagger}

From the *Department of Anesthesiology and Intensive Care, University of Muenster, Muenster, Germany; and {dagger}Mayo Clinic and Foundation, Rochester, Minnesota.

Address correspondence and reprint requests to Dirk Breukelmann, MD, University of Muenster, Klinik und Poliklinik fuer Anaesthesiologie und Operative Intensivmedizin, Albert-Schweitzer-Strasse 33, 48149 Muenster, Germany. Address e-mail to breukel{at}uni-muenster.de.

BACKGROUND: Halothane, isoflurane, and sevoflurane exert negative inotropic side effects, generally mediated via a reduced availability of intracellular calcium. Other possible mechanisms include modified intracellular calcium handling, impaired actomyosin cross-bridge cycling, and/or alteration of calcium-induced conformational changes of the regulatory troponin complex.

METHODS: We investigated the effect of halothane, isoflurane, and sevoflurane on calcium-dependent kinetics of isolated human recombinant cardiac troponin C labeled with IAANS (HrcTnCIAANS) using stopped-flow and calcium titration techniques.

RESULTS: Calcium concentration at half-maximal fluorescence intensity (Kd) in the control group was 2.1 ± 0.1 mM. Volatile anesthetics increased calcium sensitivity in a concentration-dependent fashion sevoflurane (Kd 1.5–1.7 mM, P = 0.001) > halothane (Kd 1.7–1.9 mM, P < 0.01) > isoflurane (Kd 1.8–1.9 mM, P < 0.05). The rate constant of conformational changes after rapid dissociation of calcium from HrcTnCIAANS (koff(c)) was moderately prolonged at 4°C by halothane and isoflurane > sevoflurane.

CONCLUSION: These mechanisms may counteract the effects of lower calcium availability, and can be responsible for abbreviated, and possibly incomplete, relaxation of cardiac muscle fibers in the presence of volatile anesthetics.






Lippincott, Williams & Wilkins 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 HighWire Press
Copyright © 2007 by the International Anesthesia Research Society.