Advertisement

Pflügers Archiv

, Volume 354, Issue 4, pp 339–348 | Cite as

Time- and rate-dependence of the inotropic action of noradrenaline in the isolated guinea-pig's atrium

  • Kl. Baumann
  • H. Reichel
Article

Summary

The inotropic action of noradrenaline (10−6 mol/l) was studied on a left guinea-pig's atrium which was isolated functionally by ligations and perfused during artificial stimulation (basal rhythm: 120/min) over a period of 5 to 10 hrs. Each half hour the rate was varied within a range from 60 to 300 imp/min.

Results: When noradrenaline is applied continuously throughout the experiment, contractility in terms of amplitude and rate of pressure development is almost maintained on the control level at all stimulation rates over at least 4 hrs of perfusion. When noradrenaline is applied at various stages of perfusion it compensates for the foregoing decay of contractility even after 8 hrs. Since contractility during normal perfusion decreases much more at a lower than at a higher rate the inotropic action of noradrenaline is minimal at a high rate in the fresh preparation (this means: under physiological conditions) and is fully developed only during later stages of perfusion at a low rate (which is far below the physiological range).

Key words

Atrium Inotropic Action Noradrenaline Rate-Dependence Contractility 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abbott, B. C., Mommaerts, W. F. H. M.: A study of inotropic mechanisms in the papillary muscle preparation. J. gen. Physiol.42, 533–551 (1959)Google Scholar
  2. Baird, T. J., Binnion, P. F.: Factors affecting the uptake of calcium by canine myocardial sarcoplasmic reticulum. Irish J. med. Sci.2, 585–593 (1969)Google Scholar
  3. Baumann, Kl., Reichel, H.: Time dependence of frequency potentiation in the isolated guinea-pig's atrium. Pflügers Arch.350, 69–80 (1974)Google Scholar
  4. v. Buddenbrock, W.: Vergleichende Physiologie, Bd. VI, p. 189. Basel-Stuttgart: Birkhäuser 1967Google Scholar
  5. Chidsey, C. A., Kaiser, G. A., Sonnenblick, E. H., Spann, J. F., Braunwald, E.: Cardiac norepinephrine stores in experimental heart failure in the dog. J. clin. Invest.43, 2386–2393 (1964)Google Scholar
  6. Chidsey, C. A., Sonnenblick, E. H., Morrow, A. G., Braunwald, E.: Norepinephrine stores and contractile force of papillary muscle from the failing human heart. Circulation33, 43–51 (1966)Google Scholar
  7. Cooper, T., Willman, V. L., Hanlon, C.: Drug responses of the transplanted heart. Dis. Chest45, 284–287 (1964)Google Scholar
  8. Cooper, T., Willman, V. L., Hanlon, C. R.: Influence of cardiac innervation on the response of the heart to adrenergic agents. In: Tanz, Kavaler, Roberts, eds.: Factors influencing myocardial contractility, pp. 465–478. New York-London: Academic Press 1967Google Scholar
  9. Dhalla, N. S., Bhagat, B. D., Sulakhe, P. V., Olson, R. E.: Catecholamine stores of the isolated rat heart perfused with substrate-free medium. J. Pharmacol. exp. Ther.177, 96–101 (1971)Google Scholar
  10. Dhingra, R. C., Winslow, E., Pouget, J. M., Rahimtoola, S. H., Rosen, C. M.: The effect of isoproterenol on atrioventricular and intraventricular conduction. Amer. J. Cardiol.32, 629–636 (1973)Google Scholar
  11. Furchgott, R. F., de Gubareff, T., Grossman, A.: Release of autonomic mediators in cardiac tissue by suprathreshold stimulation. Science129, 328–329 (1959)Google Scholar
  12. Furchgott, R. F., Sleator, W., de Gubareff, T.: Effects of acetylcholine and epinephrine on the contractile strength and action potential of electrically driven guinea pig atria. J. Pharmacol. exp. Ther.129, 405–416 (1960)Google Scholar
  13. Gerlings, E. D., Miller, D. T., Gilmore, J. P.: Oxygen availability: a determinant of myocardial potassium balance. Amer. J. Physiol.216, 559–562 (1969)Google Scholar
  14. Goodkind, M. J.: Myocardial contractile response to norepinephrine, isoproterenol, and calcium chloride in hyperthyroid guinea pigs. Circulat. Res.25, 237–244 (1969)Google Scholar
  15. Kavaler, F., Morad, M.: Paradoxical effects of epinephrine on excitation-contraction coupling in cardiac muscle. Circulat. Res.18, 492–501 (1966)Google Scholar
  16. Kilz, U., Schaefer, J., van Zwieten, A.: The contribution of adrenergic mechanisms to frequency potentiation and the paired stimulation in guinea-pig isolated atrial tissue. Pflügers Arch.308, 203–213 (1969)Google Scholar
  17. Koch-Weser, J.: Role of norepinephrine release in the interval-strength relationship of the heart muscle. J. Pharmacol. exp. Ther.150, 184–189 (1965)Google Scholar
  18. Langer, G. A.: Calcium exchange in the dog ventricular muscle: relation to frequency of contraction and maintenance of contractility. Circulat. Res.17, 78–89 (1965)Google Scholar
  19. Langer, G. A.: Ion fluxes in cardiac excitation and contraction and their relation to myocardial contractility. Physiol. Rev.48, 708–757 (1968)Google Scholar
  20. Langer, G. A., Brady, A. J.: Potassium in the dog ventricular muscle: kinetic studies of distribution and effects of varying frequency of contraction and potassium concentration of perfusate. Circulat. Res.18, 164–177 (1966)Google Scholar
  21. Levy, J. V., Richards, V.: Inotropic and metabolic effects of three β-adrenergic receptor blocking drugs on isolated rabbit left atria. J. Pharmacol. exp. Ther.150, 361–369 (1965)Google Scholar
  22. Lindmar, R., Muscholl, E.: Die Wirkung von Cocain, Guanethidin, Reserpin, Hexamethonium, Tetracain und Psicain auf die Noradrenalin-Freisetzung aus dem Herzen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.240, 214–227 (1961)Google Scholar
  23. Monroe, R. G., la Farge, C. G., Gamble, W. J., Hammond, R. P., Morgan, C. L.: Norepinephrine release and ventricular pressure in the isolated heart. Circulat. Res.19, 774–790 (1966)Google Scholar
  24. Niedergerke, R.: The “staircase”-phenomen and the action of calcium on the heart. J. Physiol. (Lond.)134, 569–583 (1956)Google Scholar
  25. Noble, M. I. M., Trenchard, D., Guz, A.: Left ventricular ejection in conscious dogs: II. Determinants of stroke volume. Circulat. Res.19, 148–152 (1966)Google Scholar
  26. Paul, L. T.: The effect of epinephrine on myocardial synchronization and diastolic filling time. Proc. Soc. exp. Biol. (N. Y.)140, 1197–1202 (1972)Google Scholar
  27. Reiter, M.: Differences in the inotropic cardiac effects of noradrenaline and dihydroouabain. Naunyn-Schmiedebergs Arch. Pharmacol.275, 243–250 (1972)Google Scholar
  28. Rumberger, E., Reichel, H.: The force-frequency relationship: a comparative study between warm- and cold-blooded animals. Pflügers Arch.332, 206–217 (1972)Google Scholar
  29. Rushmer, R. F.: Constancy of stroke volume in ventricular responses to exertion. Amer. J. Physiol.196, 745–750 (1959)Google Scholar
  30. Spann, J. F., Sonnenblick, E. H., Cooper, T., Chidsey, C. A., Willman, V. L., Braunwald, E.: Cardiac norepinephrine stores and the contractile state of heart muscle. Circulat. Res.19, 317–325 (1966)Google Scholar
  31. Stafford, A.: Adrenaline, anti-adrenaline drugs and potassium movements in rabbit auricles. Brit. J. Pharmacol.19, 274–285 (1962)Google Scholar
  32. Stafford, A.: Actions of adrenaline on the potassium balance of the isolated heart. Brit. J. Pharmacol.36, 571–581 (1969)Google Scholar
  33. Teiger, D. G., Farah, A.: Calcium movements in resting and stimulated isolated rabbit atria. J. Pharmacol. exp. Ther.157, 8–18 (1967)Google Scholar
  34. Toda, N.: Effects of calcium, sodium and potassium ions on contractility of isolated atria and their responses to noradrenaline. Brit. J. Pharmacol.36, 350–367 (1969)Google Scholar
  35. Trendelenburg, U.: Supersensitivity and subsensitivity to sympathomimetic amines. Pharmacol. Rev.15, 225–276 (1963)Google Scholar
  36. Tritthart, H., Kaufmann, R., Volkmer, H.-P., Bayer, R., Krause, H.: Ca-movement controlling myocardial contractility I—voltage-, current- and time-dependence of mechanical activity under voltage clamp conditions (cat papillary muscle and trabeculae). Pflügers Arch.338, 207–231 (1973)Google Scholar
  37. Tuttle, R. S., Farah, A.: The effect of ouabain on the frequency-force relation and on post-stimulation potentiation in isolated atrial and ventricular muscle. J. Pharmacol. exp. Ther.135, 142–150 (1962)Google Scholar
  38. Ullrich, K. J., Riecker, G., Kramer, K.: Das Druckvolumdiagramm des Warmblüterherzens. Pflügers Arch. ges. Physiol.259, 481–498 (1954)Google Scholar
  39. Wende, W., Henrich, H., Limbourg, P., Bauereisen, E.: Vergleichende Untersuchungen über die Wirkung adrenerger, cholinerger und durch künstlichen Antrieb verursachter Frequenzänderungen auf die Dynamik des Herzens in situ. Arch. Kreisl.-Forsch.64, 82–97 (1971)Google Scholar
  40. Westfall, T. C., Peach, M. J.: Influence of perfusion time on norepinephrine uptake, heart rate and intracellular cations in guinea pig hearts. Proc. Soc. exp. Biol. (N. Y.)142, 76–81 (1973)Google Scholar
  41. Winegrad, S., Shanes, A. M.: Calcium flux and contractility in guinea pig atria. J. gen. Physiol.45, 371–394 (1962)Google Scholar

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • Kl. Baumann
    • 1
  • H. Reichel
    • 1
  1. 1.Physiologisches Institut der Universität HamburgHamburg 20Germany

Personalised recommendations