Skip to main content
SpringerLink
Log in

Why Does Halothane Relax Cardiac Muscle but Contract Malignant Hyperthermic Skeletal Muscle?

  • Chapter
Mechanisms of Anesthetic Action in Skeletal, Cardiac, and Smooth Muscle

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 301))

Summary

We have studied the question of the possible role of sarcoplasmic reticulum (SR) in the interaction of volatile anesthetics (such as halothane, enflurane and isoflurane) with muscle. We used two cardiac muscle models, i.e., isolated rat myocytes and Langendorff perfused rat hearts. We compared the results with those for skeletal muscle SR from rabbits, rats and pigs susceptible to malignant hyperthermia (MH). In both skeletal and cardiac muscle SR, volatile anesthetics enhanced the calcium release from the SR. In cardiac muscle, these agents are known to decrease contracility (negative inotropism). We found that caffeine, a well-known agent which releases calcium from the SR, also had a negative inotropic effect in cardiac muscle, raising the possibility of an unexpected link between the potentiation of calcium release and mechanism underlying the observed negative inotropism. Current understanding of anesthetic mechanisms does not include this possibility. We further found that both volatile anesthetics and caffeine decrease the content of calcium in the SR, suggesting that the increase of calcium permeability results in the decrease of calcium ions in the SR which are available for excitation-contraction (E-C) coupling. In MH-susceptible skeletal muscle, a similar increase in calcium permeability does not cause a decrease of contractility, but rather may contribute to a fatal syndrome of temperature increase provoked by abnormal contracture. This difference may be because in skeletal myoplasm calcium ions recycle internally, while in the cardiac muscle cell they are in dynamic equilibrium with extracellular calcium ions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. S. T. Ohnishi, Calcium-induced calcium release from fragmented sarcoplasmic reticulum, J Biochem 86:1147–1150 (1979).

    PubMed  CAS  Google Scholar 

  2. S. T. Ohnishi, Calcium-Induced calcium release as a gated calcium transport, in: “Mechanism of Gated Calcium Transport Across Biological Membranes,” S. T. Ohnishi, M. Endo, eds., Academic Press, New York (1981).

    Google Scholar 

  3. S. T. Ohnishi, A. J. Waring, S. G. Fang, K. Horiuchi, J. L. Flick, K. K. Sadanaga, T. Ohnishi, Abnormal membrane properties of the sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia: Modes of action of halothane, caffeine, dantrolene and two other drugs, Arch Biochem Biophys 247:294–301, (1986).

    Article  PubMed  CAS  Google Scholar 

  4. S. T. Ohnishi, Effects of halothane, caffeine, dantrolene and tetracaine on the calcium permeability of skeletal sarcoplasmic reticulum of malignant hyperthermic pigs, Biochem Biophys Acta 897:261–268, (1987).

    Article  PubMed  CAS  Google Scholar 

  5. S. T. Ohnishi, J. L. Flick, F. Rubin, Ethanol increases calcium permeability of heavy sarcoplasmic reticulum of skeletal muscle, Arch Biochem Biophys 233:588–594, (1984).

    Article  PubMed  CAS  Google Scholar 

  6. S. T. Ohnishi, A. J. Waring, S. G. Fang, K. Horiuchi, T. Ohnishi, Sarcoplasmic reticulum membrane of rat skeletal muscle is disordered with chronic alcohol ingestion, Membr Biochem 6:49–63, (1984).

    Article  Google Scholar 

  7. S. T. Ohnishi, S. Taylor, G. A. Gronert, Calcium-induced calcium-release from sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia: The effect of halothane and dantrolene, FEBS Lett 161:103–107 (1983).

    Article  PubMed  CAS  Google Scholar 

  8. A. Fabiato, F. Fabiato, Contractions induced by a calcium triggered release of calcium from the sarcoplasmic reliculum of single skinned cardiac cells, J Physiol (Lond) 249:469–495 (1975).

    CAS  Google Scholar 

  9. W. R. Brewster, J. P. Isaacs, T. Waing-Anderson, Depressant effect of ether on myocardium of the dog and its modification by reflex release of epinephrine and norepinephrine, J Pharmacol Exp Ther 175:399–414 (1953).

    CAS  Google Scholar 

  10. H. L. Price, M. Helrich, The effect of cyclopropane, diethyl ether, nitrous oxide, thiopental and hydrogen ion concentration on the myocardial function of the dog heart-lung preparation, J Pharmacol Exp Ther 115:206–216 (1955).

    PubMed  CAS  Google Scholar 

  11. B. R. Brown, J. R. Crout, A comparative study of the effect of five general anesthetics on myocardial contractility, Anesthesiology 34:236–245 (1971).

    Article  PubMed  CAS  Google Scholar 

  12. B. F. Rusy, H. Komai, Anesthetic depression of myocardial contractility: A review of possible mechanisms, Anesthesiology 67:745–766 (1987).

    Article  PubMed  CAS  Google Scholar 

  13. H. L. Price, Calcium reverses myocardial depression caused by halothane: Site of action, Anesthesiology 218:576–579 (1974).

    Article  Google Scholar 

  14. H. L. Price, Myocardial depression by nitrous oxide and its reversal by Ca++, Anesthesiology 44:211–215 (1976).

    Article  PubMed  CAS  Google Scholar 

  15. C. Lynch, S. Vogel, N. Sperelakis, Halothane depression of myocardial slow aciton potentials, Anesthesiology 55:360–368 (1981).

    Article  PubMed  CAS  Google Scholar 

  16. Z. J. Bosnjak, J. P. Kampine, Effects of halothane, enflurane, and isoflurane on the SA node, Anesthesiology 58:314–321 (1983).

    Article  PubMed  CAS  Google Scholar 

  17. Z. J. Bosnjak, J. P. Kampine, Effects of halothane on transmembrane potentials, Ca2+ transients, and papillary muscle tension in the cat, Am J Physiol 251:H374–H381 (1986).

    PubMed  CAS  Google Scholar 

  18. C. Lynch III, Differential depression of myocardial contractility by halothane and isoflurane in vitro, Anesthesiology 64:620–631 (1986).

    Article  PubMed  CAS  Google Scholar 

  19. G. A. Langer, S. D. Serena, L. M. Nudd, Cation exchange in heart cell culture: Correlation with effects on contractile force, J Mol Cell Cardiol 6:149–161 (1974).

    Article  PubMed  CAS  Google Scholar 

  20. W. G. Nayler, J. Szeto, Effect of sodium pentobarbilal on calcium in mammalian heart muscle, Am J Physiol 222:339–344 (1972).

    PubMed  CAS  Google Scholar 

  21. E. S. Casella, N. D. A. Suite, Y. I. Fisher, T. J. J. Blanck, The effect of volatile anesthetics on the pH dependence of calcium uptake by cardiac sarcoplasmic reticulum, Anesthesiology 67:386–390 (1987).

    Article  PubMed  CAS  Google Scholar 

  22. J. Y. Su, W. G. L. Kcrrick, Effects of halothane on caffeine-induced tension transients in functionally skinned myocardial fibers, Pflugers Arch 380:29–34 (1979).

    Article  PubMed  CAS  Google Scholar 

  23. S. T. Ohnishi, C. A. DiCamillo, M. Singer, H. L. Price, Correlation between halothane-indueed myocardial depression and decreases in La3+-displaceable Ca2+ in cardiac muscle cells, J Cardiovasc Pharmacol 2:67–75 (1980).

    Article  PubMed  CAS  Google Scholar 

  24. S. T. Ohnishi, D. M. Obzansky, H. L. Price, The increase in calcium binding of cardiac plasma membrane lipoprotein caused by general anesthetics and alcohol, Can J Physiol Pharmacol 58:525–530 (1980).

    Article  PubMed  CAS  Google Scholar 

  25. B. Drenger, T. J. J. Blanck, Volatile anesthetics depress the binding of calcium channel blocker to purified cardiac sarcolemma (abstract), Anesthesiology 69:A16 (1988).

    Article  Google Scholar 

  26. Z. J. Bosnjak, F. D. Supan, N. J. Rusch, The effects of halothane, enflurane and isoflurane on calcium current in isolated canine ventricular cells, Anesthesiology 74:340–345 (1991).

    Article  PubMed  CAS  Google Scholar 

  27. M. Endo, Calcium release from the sarcoplasmic reticulum, Physiol Rev 57:71–108 (1977).

    PubMed  CAS  Google Scholar 

  28. J. L. Sutko, L. J. Thompson, A. A. Kort, E. G. Lakatta, Comparison of effects of ryanodine and caffeine on rat ventricular myocardium, Am J Physiol 250:H786–H795 (1986).

    PubMed  CAS  Google Scholar 

  29. D. M. Wheeler, R. T. Rice, R. C. Hansford, E. G. Lakatta, The effect of halothane on the free intracellular calcium concentration of isolated rat heart cells, Anesthesiology 69:578–583 (1988).

    Article  PubMed  CAS  Google Scholar 

  30. J. S. Herland, D. G. Stephenson, F. J. Julian, Halothane affects the contractile apparatus and sarcoplasmic reticulum of mechanically skinned rat ventricular fibers (abstract), Biophys J 53:335a (1988).

    Google Scholar 

  31. H. L. Price, S. T. Ohnishi, Effects of anesthetics on the heart, Fed Proc 39:575–1579 (1980).

    Google Scholar 

  32. M. Katsuoka, S. T. Ohnishi, Volatile anesthetics decrease calcium content of isolated myocytcs, Anesthesiology 70:954–960 (1989).

    Article  PubMed  CAS  Google Scholar 

  33. M. Katsuoka, S. T. Ohnishi, Inhalation anaesthetics decrease calcium content of cardiac sarcoplasmic reticulum, Br J Anaesth 62:669–673 (1989).

    Article  PubMed  CAS  Google Scholar 

  34. R. L. Kao, E. W. Christman, S. L. Luh, J. M. Kraubs, G. F. Tylers, G. H. Williams, The effects of insulin and anoxia on the metabolism of isolated mature rat cardiac myocytes, Arch Biochem Biophys 203:587–599 (1980).

    Article  PubMed  CAS  Google Scholar 

  35. G. Grynkiewiez, M. Poenie, R. Y. Tsien, A new generation of Ca2+ indicators with greatly improved fluorescence properties, J Biol Chem 260:3440–3450 (1985).

    Google Scholar 

  36. F. Renzi, B. E. Waud, Partition coefficients of volatile anesthetics in Krebs’Solution, Anesthesiology 47:62–63 (1977).

    Article  PubMed  CAS  Google Scholar 

  37. M. Endo, Mechanism of action of caffeine on the sarcoplasmic reticulum of skeletal muscle, Proc Japan Acad 51:479–484 (1975).

    CAS  Google Scholar 

  38. R. S. V. Heide, R. A. Altschuld, K. G. Lamka, C. E. Ganote, Modification of caffeine-induced injury in calcium-free perfused rat hearts, Am J Pathol 123:351–364 (1986).

    Google Scholar 

  39. E. I. Eger, Isoflurane: A review. Anesthesiology 55:559–576 (1981).

    Article  PubMed  Google Scholar 

  40. P. R. Housmans, I. Murat, Comparative effects of halothane, enflurane, and isoflurane at equipotent anesthetic concentrations on isolated ventricular myocardium of the ferret: I. Contractility, Anesthesiology 69:451–463 (1988).

    Article  PubMed  CAS  Google Scholar 

  41. M. Morad, Y. Goldman, Excitation-contraction coupling in the sarcoplasmic reticulum skinnet of tension, Prog Biophys Mol Biol 27:259–313 (1973).

    Article  Google Scholar 

  42. G. B. McClellan, S. Winegrad, The regulation of the calcium sensitivity of the contractile system in mammalian cardiac muscle. J Gen Physiol 72:737–764 (1978).

    Article  PubMed  CAS  Google Scholar 

  43. H. Reuter, C. F. Stevens, R. W. Tsien, G. Ycllin, Properties of single calcium channels in cardiac cell culture, Nature 297:501–504 (1982).

    Article  PubMed  CAS  Google Scholar 

  44. R. A. Chapman, Excitation-contraction coupling in heart muscle, Prog Biophys Mol Biol 35:1–52 (1979).

    Article  PubMed  CAS  Google Scholar 

  45. H. Reuter, Exchange of calcium ions in the mammalian myocardium: Mechanisms and physiological significance, Circ Res 34:599–606 (1974).

    PubMed  Google Scholar 

  46. P. Caroni, E. Carafoli, An ATP-dependent Ca2+-pumping system in dog heart sarcolemma, Nature 283:765–767 (1980).

    Article  PubMed  CAS  Google Scholar 

  47. E. Caraboeuf, P. Gautier, P. Guiraudou, Potential and tension changes induced by sodium removal in dog Purkinje fibers: Role of an electrogenic sodium-calcium exchange, J Physiol (Land) 311:605–622 (1981).

    Google Scholar 

  48. E. Carafoli, The homcostasis of calcium in heart cells, J Mol Cell Cardiol 17:203–212 (1985).

    Article  PubMed  CAS  Google Scholar 

  49. F. F. Jobsis, M. J. O’Connor, Calcium release and reasborption in the sartorius muscle of the toad, Biochem Biophys Res Commun 25:246–252 (1966).

    Article  PubMed  CAS  Google Scholar 

  50. S. Winegrad, Autoradiographic studies of intracellular calcium in frog skeletal muscle, J Gen Physiol 48:455–479 (1965).

    Article  PubMed  CAS  Google Scholar 

  51. S. Wincgrad, Intracellular calcium movements of frog skeletal muscle during recovery from tetanus, J Gen Physiol 51:65–83 (1968).

    Article  Google Scholar 

  52. A. J. Sweetman, A. F. Esmail, Evidence for the role of calcium ions and mitochondria in the maintenance of anesthesia in the rat, Biochem Biophys Res Commun 64:885–890 (1975).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Philadelphia Biomedical Research Institute, King of Prussia, Pennsylvania, 19406, USA

    S. Tsuyoshi Ohnishi

  2. Ihara Chemical Company, Shizuoka, Japan

    Masayuki Katsuoka

Authors
  1. S. Tsuyoshi Ohnishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masayuki Katsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, 21205, Baltimore, Maryland, USA

    Thomas J. J. Blanck  & David M. Wheeler  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Plenum Press, New York

About this chapter

Cite this chapter

Ohnishi, S.T., Katsuoka, M. (1991). Why Does Halothane Relax Cardiac Muscle but Contract Malignant Hyperthermic Skeletal Muscle?. In: Blanck, T.J.J., Wheeler, D.M. (eds) Mechanisms of Anesthetic Action in Skeletal, Cardiac, and Smooth Muscle. Advances in Experimental Medicine and Biology, vol 301. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5979-1_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-5979-1_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5981-4

  • Online ISBN: 978-1-4684-5979-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation