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Contrasting Actions of Celiprolol and Metoprolol on Cardiac Performance in Normal Volunteers

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Abstract

A double-blind, randomized, placebo-controlled comparison of metoprolol (50 mg) and celiprolol (200 mg) was undertaken in nine normal volunteers. Rest and exercise (supine bicycle) hemodynamics were assessed at 0, 2, 4, 6, and 8 hours following single oral doses of medication administered at weekly intervals. The influence of the ancillary pharmacological properties of metoprolol and celiprolol on cardiac pumping indices was assessed from heart rate and peak aortic acceleration (pkA − Exerdop). Following placebo, the heart rate and pkA increased progressively with exercise duration and workload. Following metoprolol 50 mg, the heart rate (−9.7 beat/min at 75 watts exercise) and pkA decreased. The blunting of acceleration was greater at higher exercise workloads (−6.7 m/sec2 at 75 watts exercise). Celiprolol reduced heart rate (−6.9 beat/min at 75 watts exercise) without a change in pkA. The heart rate/pkA relationship showed significant parallel displacement, downwards after metoprolol but upwards after celiprolol. Thus, for a given heart rate increment there was a greater decrease in pkA after metoprolol compared with celiprolol. The different ancillary pharmacological profiles of metoprolol and celiprolol resulted in contrasting hemodynamic profiles. The observed differences in the heart rate/pkA relationships may be attributable to the peripheral actions of these agents. The therapeutic relevance of the better maintained cardiac pumping indices on celiprolol for ischemic patients with impaired cardiac function warrants further investigation.

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References

  1. Pruss TP, Khanswala A, Wolf PS, Grebow P, Wong L. Celiprolol: A new beta adrenoceptor antagonist with novel ancillary properties. J Cardiovasc Pharmacol 1986;8(Suppl 4):S29-S32.

    Google Scholar 

  2. Tham TCK, Riddell JG, Shanks RG. The effect of increasing doses of celiprolol on sleeping heart rate and quality of sleep in man. Clin Pharmacol Ther 1991;49:187:PIII-54.

    Google Scholar 

  3. Lamon KD. Clinical safety and efficacy of celiprolol. Am Heart J 1991;121:683-687.

    Google Scholar 

  4. Heublein B, Modersohn D, Franz N, Panzner B. Acute haemodynamic profile of celiprolol in patients with coronary heart disease and hypertension: A double blind comparison with metoprolol. Eur Heart J 1991;12:617-623.

    Google Scholar 

  5. Mancia G, Grassi G, Parati G, et al. Effects of celiprolol on reflex control of the cardiovascular system in essential hypertension. J Cardiovasc Pharmacol 1986;8(Suppl 4):S67-S74.

    Google Scholar 

  6. McLenachan JM, Grant S, Ford I, Henderson E, Dargie HJ. Submaximal, but not maximal, exercise testing detects differences in the effects of beta-blockers during treadmill exercise: A study of celiprolol and atenolol. Am Heart J 1991;121:691-695.

    Google Scholar 

  7. McDevitt DG, Brown CH, Carruthers GS, Shanks RG. Influence of intrinsic sympathomimetic activity and cardioselectivity on beta-adrenoceptor blockade. J Clin Pharmacol 1977;21:556-566.

    Google Scholar 

  8. Wheeldon NM, McDevitt DG, Lipworth BJ. Evaluation of in vivo partial beta1/beta2-agonist activity: A dose-ranging study with carteolol. Br J Clin Pharmacol 1992;33:411-416.

    Google Scholar 

  9. Wheeldon NM, McDevitt DG, Lipworth BJ. Selectivity of antagonist and partial agonist activity of celiprolol in normal subjects. Br J Clin Pharmacol 1992;34:337-343.

    Google Scholar 

  10. Kolettis M, Jenkins BS, Webb-Peploe MM. Assessment of left ventricular function by indices derived from aortic flow velocity. Br Heart J 1984;38:18-31.

    Google Scholar 

  11. Bennett ED, Barclay SA, Davis AI, Mannering D, Mehta N. Ascending aortic blood velocity and acceleration using Doppler ultrasound in the assessment of left ventricular function. Cardiovasc Res 1984;18:632-638.

    Google Scholar 

  12. Clifton DG, Harrison MR, DeMaria AN. Influence of beta adrenergic blockade upon hemodynamic response to exercise assessed by Doppler echocardiography. Am Heart J 1990;120:579-584.

    Google Scholar 

  13. Mehta N, Boyle G, Bennet D, Gilmour S, Noble MIM, Mills CM, Pugh S. Haemodynamic response to treadmill exercise in normal volunteers: An assessment by Doppler ultrasonic measurement of ascending aortic blood velocity and acceleration. Am Heart J 1988;116:1298,1307.

    Google Scholar 

  14. Bojanowski LMR, Timmis AD, Najm YC, Gosling RG. Pulsed Doppler ultrasound compared with thermodilution for monitoring cardiac output responses to changing left ventricular function. Cardiovasc Res 1987;21:260-268.

    Google Scholar 

  15. Bedotto JB, Eichhorn EJ, Grayburn PA. Effects of left ventricular preload and afterload on ascending aortic blood velocity and acceleration in coronary artery disease. Am J Cardiol 1989;64:856-859.

    Google Scholar 

  16. Gardin JM. Doppler measurements of aortic blood flow velocity and acceleration: Load-independent indexes of left ventricular performance? Am J Cardiol 1989;64:935-936.

    Google Scholar 

  17. Harrison MR, Clifton GD, Berk MR, DeMaria AN. Effect of systolic blood pressure and afterload on Doppler echocardiographic measurements of systolic function in normal subjects. Am J Cardiol 1989;64:905-908.

    Google Scholar 

  18. Silke B, Thompson A, Leitch A, Riddell JG. A placebo controlled comparison of the effects of metoprolol and celiprolol on echo-Doppler measurements of cardiovascular function in normal volunteers. Br J Clin Pharmacol 1995;40:37-42.

    Google Scholar 

  19. Wheeldon NM, McDevitt DG, Lipworth BJ. Selectivity of antagonist and partial agonist effects of celiprolol in normal subjects. Br J Clin Pharmac 34:337-343.

  20. Harron DWG, Balnave K, Kinney CD, Wilson R, Russell CJ, Shanks RG. Effects on exercise tachycardia during forty-eight hours of a series of doses of atenolol, sotalol, and metoprolol. J Clin Pharmacol 1981;29:259-302.

    Google Scholar 

  21. Jassal V, Harris CM, Silke B. Reproducibility of a new continuous echo-Doppler method (Exerdop) in man. Br J Clin Pharmacol 1993;35:87P.

    Google Scholar 

  22. Ramsey M. Non-invasive automatic determination of mean arterial blood pressure. Med Biol Eng Comput 1979;17:11-18.

    Google Scholar 

  23. Hutton P, Dye J, Prys-Roberts C. An assessment of the Dinamap 845. Anaesthesia 1984;39:261-267.

    Google Scholar 

  24. Winer BJ. Statistical Principles in Experimental Design, 2nd. ed. New York: McGraw-Hill, 1971.

    Google Scholar 

  25. Altman DG, Gardner MJ. Calculating confidence intervals for regression and correlation. Br Med J 1988;296:1238-1242.

    Google Scholar 

  26. Zar JH. Multiple regression and correlation. In: Biostatistical Analysis, 2nd ed. Englewood Cliffs, NJ: Prentice-Hall, 1984.

    Google Scholar 

  27. Wheeldon NM, McDevitt DG, Lipworth BJ. Evaluation of the selectivity of antagonist and partial agonist effects of celiprolol in normal subjects. Br J Clin Pharmacol 1992;33:528P.

    Google Scholar 

  28. Harry JD, Millson DS, Morton PB. Use of Doppler echocardiography to determine the cardiac effects of dobutamine in volunteers. J Pharm Med 1988;3:173-183.

    Google Scholar 

  29. de Mey C, Belz GG, Nixdorf U, Butzer R, Schroeter V, Meyer J, Erbel R. Relative sensitivity of four non-invasive methods in assessing systolic cardiovascular effects of isoproterenol in healthy volunteers. Clin Pharmacol Ther 1992;52:609-619.

    Google Scholar 

  30. Harrison MR, Clifton GD, DeMaria AN. Hemodynamics effects of calcium channel and beta-receptor antagonists: Evaluation by Doppler echocardiography. Am Heart J 1990;121:126-133.

    Google Scholar 

  31. Clifton DG, Pennel AT, Harrison MR. Pharmacodynamics of propranolol on left ventricular function: Assessment by Doppler echocardiography. Clin Pharmacol Ther 1990;48:431-438.

    Google Scholar 

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Silke, B., Thompson, A. & Riddell, J. Contrasting Actions of Celiprolol and Metoprolol on Cardiac Performance in Normal Volunteers. Cardiovasc Drugs Ther 11, 57–61 (1997). https://doi.org/10.1023/A:1007799807554

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