Skip to main content

Advertisement

SpringerLink
Log in

Landiolol has a less potent negative inotropic effect than esmolol in isolated rabbit hearts

  • Original Article
  • Published:
Journal of Anesthesia Aims and scope Submit manuscript

Abstract

Purpose

We compared the negative chronotropic and inotropic effects of landiolol and esmolol, two clinically available short-acting β1-blockers with high β1-selectivity, using whole isolated rabbit heart preparations.

Methods

Tachycardia was induced by continuous perfusion of 10−7 M isoproterenol, and we used concentrations of landiolol or esmolol in ascending steps (1 · 10−6, 3 · 10−6, 1 · 10−5, 3 · 10−5, and 1 · 10−4 M). Heart rate (HR), left ventricular developed pressure (LVDP), the maximal rates of left ventricular force development (LVdP/dtmax), and myocardial oxygen consumption (MVO2) were measured and compared.

Results

Both landiolol and esmolol produced dosedependent decreases in HR, LVDP, LVdP/dtmax, and MVO2. The HR lowering effects of the two agents were comparable. At concentrations of 3 · 10−5 and 1 · 10−4 M, esmolol produced more profound depression of LVDP (47 ± 26 and 12 ± 11 mmHg, respectively; mean ± SD) and reduction of LVdP/dtmax (650 ± 287 and 120 ± 103 mmHg·s−1) than landiolol (68 ± 20 and 64 ± 20 mmHg, and 897 ± 236 and 852 ± 240 mmHg·s−1, respectively). At the same concentrations, esmolol caused more profound reduction in MVO2 (40 ± 11 and 35 ± 10 μl·min−1 · g−1) than landiolol (50 ± 8 and 48 ± 8 μl·min−1 · g−1), respectively.

Conclusion

Our results indicate that in the isolated rabbit heart, landiolol and esmolol had equipotent negative chronotropic effects, however, landiolol had a less potent negative inotropic effect than esmolol.

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. Wallace A, Layug B, Tateo I, Li J, Hollenberg M, Browner W, Miller D, Mangano DT. Prophylactic atenolol reduces postoperative myocardial ischemia. McSPI Research Group. Anesthesiology. 1998;88:7–17.

    Article  PubMed  CAS  Google Scholar 

  2. Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med. 1996;335:1713–1720.

    Article  PubMed  CAS  Google Scholar 

  3. American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery); American Society of Echocardiography; American Society of Nuclear Cardiology; Heart Rhythm Society; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society for Vascular Surgery, Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE, Freeman WK, Froehlich JB, Kasper EK, Kersten JR, Riegel B, Robb JF, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Buller CE, Creager MA, Ettinger SM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Anesth Analg. 2008;106:685–712.

    PubMed  Google Scholar 

  4. Gorczynski RJ. Basic pharmacology of esmolol. Am J Cardiol. 1985;56:3F–13F.

    Article  PubMed  CAS  Google Scholar 

  5. Kirshenbaum JM, Kloner RA, Antman EM, Braunwald E. Use of an ultra short-acting beta-blocker in patients with acute myocardial ischemia. Circulation. 1985;72:873–880.

    PubMed  CAS  Google Scholar 

  6. Jacobs JR, Maier GW, Rankin JS, Reves JG. Esmolol and left ventricular function in the awake dog. Anesthesiology. 1985;68:373–378.

    Article  Google Scholar 

  7. Deegan R, Wood AJ. Beta-receptor antagonism does not fully explain esmolol-induced hypotension. Clin Pharmacol Ther. 1994;56:223–228.

    PubMed  CAS  Google Scholar 

  8. Iguchi S, Iwamura H, Nishizaki M, Hayashi A, Senokuchi K, Kobayashi K, Sakaki K, Hachiya K, Ichioka Y, Kawamura M. Development of a highly cardioselective ultra short-acting beta-blocker, ONO-1101. Chem Pharm Bull. 1992;40:1462–1469.

    PubMed  CAS  Google Scholar 

  9. Sasao J, Tarver SD, Kindscher JD, Taneyama C, Benson KT, Goto H. In rabbits, landiolol, a new ultra-short-acting β-blocker, exerts a more potent negative chronotropic effect and less effect on blood pressure than esmolol. Can J Anaesth. 2001;48:985–989.

    PubMed  CAS  Google Scholar 

  10. Motomura S, Hagihara A, Narumi Y, Hashimoto K. Time course of a new ultrashort-acting beta-adrenoceptor-blocking drug, ONO-1101: comparison with those of esmolol and propranolol by using the canine isolated, blood-perfused heart preparations. J Cardiovasc Pharmacol. 1998;31:431–440.

    Article  PubMed  CAS  Google Scholar 

  11. Sugiyama A, Takahara A, Hashimoto K. Electrophysiologic, cardiohemodynamic and beta-blocking actions of a new ultrashort-acting beta-blocker, ONO-1101, assessed by the in vivo canine model in comparison with esmolol. J Cardiovasc Pharmacol. 1999;34:70–77.

    Article  PubMed  CAS  Google Scholar 

  12. Riess ML, Kevin LG, Camara AK, Heisner JS, Stowe DF. Dual exposure to sevoflurane improves anesthetic preconditioning in intact hearts. Anesthesiology. 2004;100:569–574.

    Article  PubMed  CAS  Google Scholar 

  13. Murakami M, Furuie H, Matsuguma K, Wanibuchi A, Kikawa S, Irie S. Pharmacokinetics and pharmacodynamics of landiolol hydrochloride, an ultra short-acting beta1-selective blocker, in a dose escalation regimen in healthy male volunteers. Drug Metab Pharmacokinet. 2005;20:337–344.

    Article  PubMed  CAS  Google Scholar 

  14. Tsunekawa K, Imawaka H, Yamamoto K, Shibakawa K, Hiraku S. Studies on the metabolic fate of ultra short acting β1 blocker ONO-1101 (3): metabolism and protein binding (in Japanese with English abstract). Xenobio Metab Dispos. 1997;12:31–41.

    CAS  Google Scholar 

  15. Sum CY, Yacobi A. Gas chromatographic-mass spectrometric assay for the ultra-short-acting beta-blocker esmolol. J Pharm Sci. 1984;73:1177–1179.

    Article  PubMed  CAS  Google Scholar 

  16. Reynolds RD, Gorczynski RJ, Quon CY. Pharmacology and pharmacokinetics of esmolol. J Clin Pharmacol. 1986;26(Suppl A):A3–A14.

    PubMed  CAS  Google Scholar 

  17. Su Z, Li F, Spitzer KW, Yao A, Ritter M, Barry WH. Comparison of sarcoplasmic reticulum Ca2+-ATPase function in human, dog, rabbit, and mouse ventricular myocytes. J Mol Cell Cardiol. 2003;35:761–767.

    Article  PubMed  CAS  Google Scholar 

  18. Arlock P, Wohlfart B, Sjoberg T, Steen S. The negative inotropic effect of esmolol on isolated cardiac muscle. Scand Cardiovasc J. 2005;39:250–254.

    Article  PubMed  CAS  Google Scholar 

  19. Deng CY, Lin SG, Zhang WC, Kuang SJ, Qian WM, Wu SL, Shan ZX, Yang M, Yu XY. Esmolol inhibits Na+ current in rat ventricular myocytes. Methods Find Exp Clin Pharmacol. 2006;28:697–702.

    Article  PubMed  CAS  Google Scholar 

  20. Kuhn-Regnier F, Natour E, Dhein S, Dapunt O, Geissler HJ, LaRose K, Gorg C, Mehlhorn U. Beta-blockade versus Buckberg blood-cardioplegia in coronary bypass operation. Eur J Cardiothorac Surg. 1999;15:67–74.

    Article  PubMed  CAS  Google Scholar 

  21. Bessho R, Chambers DJ. Myocardial protection: the efficacy of an ultra-short-acting beta-blocker, esmolol, as a cardioplegic agent. J Thorac Cardiovasc Surg. 2001;122:993–1003.

    Article  PubMed  CAS  Google Scholar 

  22. Muraki K, Nakagawa H, Nagano N, Henmi S, Kawasumi H, Nakanishi T, Imaizumi K, Tokuno T, Atsuki K, Imaizumi Y, Watanabe M. Effects of ONO-1101, a novel beta-antagonist, on action potential and membrane currents in cardiac muscle. J Pharmacol Exp Ther. 1996;278:555–563.

    PubMed  CAS  Google Scholar 

  23. Yamazaki A, Kinoshita H, Shimogai M, Fujii K, Nakahata K, Hironaka Y, Iranami H, Hatano Y. Landiolol attenuates tachycardia in response to endotracheal intubation without affecting blood pressure. Can J Anaesth. 2005;52:254–257.

    Article  PubMed  Google Scholar 

  24. Biccard BM. Peri-operative beta-blockade and haemodynamic optimization in patients with coronary artery disease and decreasing exercise capacity presenting for major noncardiac surgery. Anaesthesia. 2004;59:60–68.

    Article  PubMed  CAS  Google Scholar 

  25. London MJ, Zaugg M, Schaub MC, Spahn DR. Perioperative beta-adrenergic receptor blockade: physiologic foundations and clinical controversies. Anesthesiology. 2004;100:170–175.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Yao Tokusyukai General Hospital, 3-15-38 Kyuhoji, Yao, Osaka, 581-0072, Japan

    Kazutoshi Ikeshita, Sumiko Toriyama, Tomoyuki Yamashita & Yoshiyuki Tani

  2. Department of Anesthesiology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Kiyonobu Nishikawa, Tokuhiro Yamada & Akira Asada

Authors
  1. Kazutoshi Ikeshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kiyonobu Nishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sumiko Toriyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tomoyuki Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshiyuki Tani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tokuhiro Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Akira Asada
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Ikeshita, K., Nishikawa, K., Toriyama, S. et al. Landiolol has a less potent negative inotropic effect than esmolol in isolated rabbit hearts. J Anesth 22, 361–366 (2008). https://doi.org/10.1007/s00540-008-0640-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00540-008-0640-4

Key words

Search

Navigation