Skip to main content
SpringerLink
Log in

The effects of calcium antagonists on extracellular potassium accumulation during global ischaemia in isolated perfused rat hearts

  • Calcium Antagonists
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Summary

The effects of equipotent concentrations of diltiazem, verapamil, and nifedipine upon the accumulation of extracellular potassium [K+]out and the left ventricular pressure (LVP) were studied during global ischemia in isolated perfused rat hearts. Measurement of [K+]out and LVP were performed in two series of experiments. Diltiazem (2×10-6, 3×10-6, and 10-5M), verapamil (3×10-8, 10-7, and 3×10-7 M), and nifedipine (3×10-8, 10-7, and 1.5×10-7 M) were able to slow, in a concentration-dependent manner, the initial rate of rise of [K+]out without affecting the final plateau value of [K+]out reached at t=5 to t=10 minutes. Notably, at the lowest concentrations, which slightly influenced LVP diltiazem, verapamil, and to a lesser degree nifedipine, were still able to slow the rise in [K+]out. In addition, after preper-fusion with low-calcium media ([Ca2+] from 1.8 to 1.3 or 0.9 mM), inducing similar negative inotropic effects as those of the calcium antagonists, the rise in [K+]out was not significantly influenced. Our data indicate that the ability to slow the rise in [K+]out is a specific characteristic of calcium antagonists that is independent of their negative inotropic effects.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Coronel R, Fiolet JWT, Wilms-Schopman FJG, et al. Distribution of extracellular potassium and its relation to electrophysiologic changes during acute myocardial ischemia in the isolated perfused porcine heart. Circulation 1988;77:1125–1138.

    Google Scholar 

  2. Hill JL, Gettes LW. Effect of acute coronary artery occlusion on local myocardial extracellular K+ activity in swine. Circulation 1980;61:768–778.

    Google Scholar 

  3. Harris AS, Bisteni A, Russell RA, et al. Excitatory factors in ventricular tachycardia resulting from myocardial ischemia. Potassium a major excitant. Science 1954;119:200–203.

    Google Scholar 

  4. Hirche HJ, Franz CHR, Bos L, et al. Myocardial extracellular K+ and H+ increase and noradrenaline release as possible cause of early arrhythmias following acute coronary artery occlusion in pigs. J Mol Cell Cardiol 1980;12:579–593.

    Google Scholar 

  5. Blake K, Clusin WT. Effect of diltiazem on ischaemic myocardial depolarization and extracellular K+ accumulation. Eur J Pharmacol 1986;127:261–265.

    Google Scholar 

  6. Kirchengast M, Raschack M. Effects of gallopamil, diltiazem and nifedipine on the loss of K+ from ischaemic pig hearts. Eur J Pharmacol 1989;160:349–358.

    Google Scholar 

  7. Lopez JF, Orchard RC. Effects of verapamil on the extracellular K+ rise during myocardial ischaemia in dogs. Cardiovasc Ress 1985;19:363–369.

    Google Scholar 

  8. Fleet WF, Johnson TA, Graebner LA, et al. Effects of verapamil on ischaemic-induced changes in extracellular K+, pH and local activation in the pig. Circulation 1986;83:837–846.

    Google Scholar 

  9. Budder M, Kirchengast M, Zhang KM, Meesmann W. Effects of the calcium antagonist gallopamil on the increase of myocardial extracellular potassium activity during LAD occlusion in dogs. Basic Res Cardiol 1987;82:279–289.

    Google Scholar 

  10. Grover GJ, Sleph PG. Dissociation of cardiodepression from cardiodepression with calcium antagonists: Diltiazem protects ischemic rat myocardium with a lower functional cost as compared with verapamil or nifedipine. J Cardiovasc Pharmacol 1989;14:331–340.

    Google Scholar 

  11. Watts JA, Mairano LJ, Maiorano PC. Comparison of the protective effects of verapamil, diltiazem, nifedipine, and buffer containing low calcium upon global myocardial ischaemic injury. J Mol Cell Cardiol 1986;18:255–263.

    Google Scholar 

  12. Cascio WE, Yan G, Kleber AG. Passive electrical properties, mechanical activity, and extracellular potassium in arterially perfused and ischemic rabbit ventricular muscle: Effects of calcium entry blockade or hypocalcemia. Circ Res 1990;66:1461–1473.

    Google Scholar 

  13. Wilensky R, Tranum-Jensen J, Coronel R, et al. The subendocardial border zone during acute ischemia of the rabbit heart: An electrophysiological, metabolic, and morphologic correlative study. Circulation 1986;74:1137–1146.

    Google Scholar 

  14. Knopf H, Theising R, Hirche HJ. The effect of desipramine on ischemia-induced changes in extracellular K+, Na+ and H+ concentrations and noradrenaline release in the isolated rat heart during global ischemia. J Cardiovasc Pharmacol 1988;12(Suppl 1):S8-S14.

    Google Scholar 

  15. Kleber AG. Resting membrane potential, extracellular potassium activity, and intracellular sodium activity during acute global ischemia in isolated perfused guinea-pig hearts. Circ Res 1983;52:442–450.

    Google Scholar 

  16. Rau EE, Shine KI, Langer GA. Potassium exchange and mechanical performance in anoxic mammalian myocardium. Am J Physiol 1977;232:H85-H94.

    Google Scholar 

  17. Isenberg G. Cardiac purkinje fibres: [Ca2+]i controls steady state potassium conductance. Pflügers Arch 1977;371:71–76.

    Google Scholar 

  18. Gaspardone A, Shine KI, Seabrooke SR, Poole-Wilson PA. Potassium loss from rabbit myocardium during hypoxia: Evidence for passive efflux linked to anion extrusion. J Mol Cell Cardiol 1985;18:389–399.

    Google Scholar 

  19. Crake T, Kirby MS, Poole-Wilson PA. Potassium efflux from the myocardium during hypoxia: Role of lactate ions. Cardiovasc Res 1987;21:886–891.

    Google Scholar 

  20. Poole-Wilson PA, Langer GA. Effect of pH on ionic exchange and function in rat and rabbit myocardium. Am J Physiol 1975;229:570–581.

    Google Scholar 

  21. Skinner RB, Kunze DL. Changes in extracellular potassium activity in response to decreased pH in rabbit atrial muscle. Circ Res 1976;39:678–683.

    Google Scholar 

  22. Kleber AG, Riegger CB, Janse MJ. Extracellular K+ and H+ shifts in early ischemia: Mechanisms and relation to changes in impulse propagation. J Mol Cell Cardiol 1987; 19(Suppl 5):35–44.

    Google Scholar 

  23. Noma A. ATP-regulated K+ channels in cardiac muscles. Nature 1983;305:147–148.

    Google Scholar 

  24. Noma A, Shibasaki T. Membrane current through adenosine-triphosphate-regulated potassium channels in guineapig ventricular cells. J Physiol 1985;363:463–480.

    Google Scholar 

  25. Kantor PF, Coetzee WA, Carmeliet EE, et al. Reduction of ischemic K+ loss and arrhythmias in rat hearts: Effect of glibenclamide, a sulfonylurea. Circ Res 1990;66:478–485.

    Google Scholar 

  26. Hamm CW, Opie LH. Protective effects of verapamil, nifedipine, and diltiazem in coronary-ligated, isolated working rat heart. Circ Res 1983;52(Suppl 1): 29–38.

    Google Scholar 

  27. Curtis MJ, Walker MJA. The mechanism of action of the optical enantiomers of verapamil against ischaemia-induced arrhythmias in the conscious rat. Br J Pharmacol 1986; 89:137–147.

    Google Scholar 

  28. Herzig S, Wansora G. The cardiodepressant action of gallopamil depends upon the extracellular K+ concentration. Naunyn-Schmiedeberg's Arch Pharmacol 1988;337(Suppl): R54.

    Google Scholar 

  29. Knopf H, Theising R, Moon CH, Hirche HJ. Continuous determination of extracellular space and changes of K+, Na+, Ca2+, and H+ during global ischaemia in isolated rat hearts. J Mol Cell Cardiol 1990;22:1259–1272.

    Google Scholar 

  30. Fiolet JWT, Baartscheer A, Scumacher CA, et al. The change of the free energy of ATP hydrolysis during global ischemia and anoxia in the rat heart. Its possible role in the regulation of the transsarcolemmal sodium and potassium gradients. J Mol Cell Cardiol 1984;16:1023–1036.

    Google Scholar 

  31. Tranum-Jensen J, Janse MJ, Fiolet JWT, Krieger WJG. Tissue osmolality, cell swelling, and reperfusion in acute regional myocardial ischemia in the isolated porcine heart. Circ Res 1981;49:364–381.

    Google Scholar 

  32. Hugtenburg JG, Mathy MJ, Boddeke HWGM, et al. Differences between negative inotropic and vasodilator effects of calcium antagonists on extra- and intracellular calcium movements in rat and guinea-pig cardiac preparations. Naunyn-Schmiedeberg's Arch Pharmacol 1989;340:567–575.

    Google Scholar 

  33. Schaapherder AFM, Schumacher CA, Coronel R, Fiolet JWT. Transmural inhomogeneity of extracellular [K+] and pH and myocardial energy metabolism in the isolated rat heart during acute global ischemia; dependence on gaseous environment. Basic Res Cardiol 1990;85:33–44.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacotherapy, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands

    J. B. Heijnis & P. A. van Zwieten

  2. Department of Clinical and Experimental Cardiology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands

    R. Coronel

  3. Department of Pharmacotherapy, University of Amsterdam, Academic Medical Center, Meibergdreef 15, 1105, Amsterdam, The Netherlands

    J. B. Heijnis

Authors
  1. J. B. Heijnis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Coronel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. A. van Zwieten
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heijnis, J.B., Coronel, R. & van Zwieten, P.A. The effects of calcium antagonists on extracellular potassium accumulation during global ischaemia in isolated perfused rat hearts. Cardiovasc Drug Ther 5, 1035–1041 (1991). https://doi.org/10.1007/BF00143532

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00143532

Key Words

Search

Navigation