Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1986 Dec;22(6):697–706. doi: 10.1111/j.1365-2125.1986.tb02960.x

A rest and exercise haemodynamic evaluation of a new cardio-selective beta-adrenoceptor blocker celiprolol alone and in combination with nitroglycerine in ischaemic heart disease.

B Silke, S P Verma, M A Frais, G Reynolds, S H Taylor
PMCID: PMC1401208  PMID: 2882772

Abstract

The symptomatic benefits of combining beta-adrenoceptor blockers and nitrates in angina pectoris are well recognised. Their actions on cardiac haemodynamics and volumes when combined have been poorly characterized. Accordingly this study investigated a new cardioselective beta-adrenoceptor blocking agent celiprolol and buccal nitroglycerine in 24 patients with angiographically documented coronary artery disease. Following a control period, with confirmed stable haemodynamics, three groups (n = 8/group) of prospectively matched patients, were studied following intravenous celiprolol (8 mg), buccal nitrate (10 mg) or their combination. Haemodynamics and left ventricular ejection fraction (nuclear probe) were determined following each intervention. The actions of each regimen on the haemodynamics of exercise-induced angina were compared by exercise testing in the control state and following each regimen. At rest, celiprolol did not alter haemodynamic parameters. Nitrate therapy reduced left ventricular filling pressure (pulmonary artery occluded pressure--PAOP) and volumes; the ejection fraction and heart rate increased. Combination therapy resulted in a highly significant reduction in left ventricular preload and afterload (PAOP and mean arterial blood pressure) at an increased left ventricular ejection fraction and reduced cardiac volumes; there was a trend to reduce cardiac double product (HR X SBP). During exercise celiprolol reduced systolic blood pressure, heart rate and cardiac index; systemic vascular resistance index increased. Nitrate therapy reduced blood pressure and PAOP, and increased ejection fraction. Combination therapy reduced all components of the triple product (heart rate, systolic blood pressure and PAOP) without affecting the other haemodynamic or radionuclide parameters. These data suggest improvements in cardiac function from the combination of celiprolol and nitrate therapy which were not achieved by either agent when used as monotherapy; they afford an interesting insight into the manner in which such widely utilised therapeutic modalities interact in coronary artery disease.

Full text

PDF
697

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bacharach S. L., Green M. V., Borer J. S., Ostrow H. G., Redwood D. R., Johnston G. S. ECG-gated scintillation probe measurement of left ventricular function. J Nucl Med. 1977 Dec;18(12):1176–1183. [PubMed] [Google Scholar]
  2. Berger H. J., Davies R. A., Batsford W. P., Hoffer P. B., Gottschalk A., Zaret B. L. Beat-to-beat left ventricular performance assessed from the equilibrium cardiac blood pool using a computerized nuclear probe. Circulation. 1981 Jan;63(1):133–142. doi: 10.1161/01.cir.63.1.133. [DOI] [PubMed] [Google Scholar]
  3. CHRISTENSSON B., KARLEFORS T., WESTLING H. HAEMODYNAMIC EFFECTS OF NITROGLYCERIN IN PATIENTS WITH CORONARY HEART DISEASE. Br Heart J. 1965 Jul;27:511–519. doi: 10.1136/hrt.27.4.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Feild B. J., Russell R. O., Jr, Dowling J. T., Rackley C. E. Regional left ventricular performance in the year following myocardial infarction. Circulation. 1972 Oct;46(4):679–689. doi: 10.1161/01.cir.46.4.679. [DOI] [PubMed] [Google Scholar]
  5. Forrester J. S., Ganz W., Diamond G., McHugh T., Chonette D. W., Swan H. J. Thermodilution cardiac output determination with a single flow-directed catheter. Am Heart J. 1972 Mar;83(3):306–311. doi: 10.1016/0002-8703(72)90429-2. [DOI] [PubMed] [Google Scholar]
  6. Hendry W. G., Silke B., Taylor S. H. Haemodynamic dose-response effects of i.v. metoprolol in coronary heart disease. Eur J Clin Pharmacol. 1981;19(5):323–327. doi: 10.1007/BF00544581. [DOI] [PubMed] [Google Scholar]
  7. Hoel B. L. Some aspects of the clinical use of thermodilution in measuring cardiac output. With particular reference to the Swan-Ganz thermodilution catheters. Scand J Clin Lab Invest. 1978 Jun;38(4):383–388. doi: 10.3109/00365517809108438. [DOI] [PubMed] [Google Scholar]
  8. Lahiri A., Bowles M. J., Jones R. I., Crawley J. C., Raftery E. B. Assessment of left ventricular function in coronary artery disease with the nuclear probe during intervention studies. Br Heart J. 1984 Oct;52(4):422–430. doi: 10.1136/hrt.52.4.422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Links J. M., Becker L. C., Shindledecker J. G., Guzman P., Burow R. D., Nickoloff E. L., Alderson P. O., Wagner H. N. Measurement of absolute left ventricular volume from gated blood pool studies. Circulation. 1982 Jan;65(1):82–91. doi: 10.1161/01.cir.65.1.82. [DOI] [PubMed] [Google Scholar]
  10. Mann T., Brodie B. R., Grossman W., McLaurin L. P. Effect of angina on the left ventricular diastolic pressure-volume relationship. Circulation. 1977 May;55(5):761–766. doi: 10.1161/01.cir.55.5.761. [DOI] [PubMed] [Google Scholar]
  11. McAnulty J. H., Hattenhauer M. T., Rösch J., Kloster F. E., Rahimtoola S. H. Improvement in left ventricular wall motion following nitroglycerin. Circulation. 1975 Jan;51(1):140–145. doi: 10.1161/01.cir.51.1.140. [DOI] [PubMed] [Google Scholar]
  12. McKay R. G., Aroesty J. M., Heller G. V., Royal H., Parker J. A., Silverman K. J., Kolodny G. M., Grossman W. Left ventricular pressure-volume diagrams and end-systolic pressure-volume relations in human beings. J Am Coll Cardiol. 1984 Feb;3(2 Pt 1):301–312. doi: 10.1016/s0735-1097(84)80013-3. [DOI] [PubMed] [Google Scholar]
  13. Najmi M., Griggs D. M., Jr, Kasparian H., Novack P. Effects of nitroglycerin on hemodynamics during rest and exercise in patients with coronary insufficiency. Circulation. 1967 Jan;35(1):46–54. doi: 10.1161/01.cir.35.1.46. [DOI] [PubMed] [Google Scholar]
  14. Parker J. O., Di Giorgi S., West R. O. A hemodynamic study of acute coronary insufficiency precipitated by exercise. With observations on the effects of nitroglycerin. Am J Cardiol. 1966 Apr;17(4):470–483. doi: 10.1016/0002-9149(66)90237-2. [DOI] [PubMed] [Google Scholar]
  15. Parker J. O., West R. O., Di Giorgi S. The effect of nitroglycerin on coronary blood flow and the hemodynamic response to exercise in coronary artery disease. Am J Cardiol. 1971 Jan;27(1):59–65. doi: 10.1016/0002-9149(71)90083-x. [DOI] [PubMed] [Google Scholar]
  16. Prichard B. N., Aellig W. H., Richardson G. A. The action of intravenous oxprenolol, practolol, propranolol and sotalol on acute exercise tolerance in angina pectoris: the effect on heart rate and the electrocardiogram. Postgrad Med J. 1970 Nov;(Suppl):77–85. [PubMed] [Google Scholar]
  17. Rackley C. E., Dear H. D., Baxley W. A., Jones W. B., Dodge H. T. Left ventricular chamber volume, mass, and function in severe coronary artery disease. Circulation. 1970 Apr;41(4):605–613. doi: 10.1161/01.cir.41.4.605. [DOI] [PubMed] [Google Scholar]
  18. Schwarz F., Ensslen R., Thormann J., Schlepper M. Abolished compensation of cardiac performance after nitroglycerin in patients with ventricular asynergy. Am Heart J. 1977 Oct;94(4):421–427. doi: 10.1016/s0002-8703(77)80034-3. [DOI] [PubMed] [Google Scholar]
  19. Shah R., Bodenheimer M. M., Banka V. S., Helfant R. H. Nitroglycerin and ventricular performance. Differential effect in the presence of reversible and irreversible asynergy. Chest. 1976 Oct;70(4):473–479. doi: 10.1378/chest.70.4.473. [DOI] [PubMed] [Google Scholar]
  20. Silke B., Hilal A., Taylor S. H. Haemodynamic dose-response effects of intravenous oxprenolol in coronary heart disease. J Cardiovasc Pharmacol. 1981 Jul-Aug;3(4):716–727. doi: 10.1097/00005344-198107000-00006. [DOI] [PubMed] [Google Scholar]
  21. Silke B., Verma S. P., Frais M. A., Hafizullah M., Taylor S. H. Effects of buccal nitrate on left ventricular haemodynamics and volume at rest and during exercise-induced angina. Br J Clin Pharmacol. 1985 Nov;20(5):437–445. doi: 10.1111/j.1365-2125.1985.tb05094.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Silke B., Verma S. P., Frais M. A., Reynolds G., Jackson N., Taylor S. H. Haemodynamic analysis of the effects of nicardipine and metoprolol alone and in combination in coronary artery disease. Eur Heart J. 1985 Nov;6(11):930–938. doi: 10.1093/oxfordjournals.eurheartj.a061790. [DOI] [PubMed] [Google Scholar]
  23. Silke B., Verma S. P., Frais M. A., Reynolds G., Taylor S. H. Differential actions of atenolol and celiprolol on cardiac performance in ischemic heart disease. J Cardiovasc Pharmacol. 1986;8 (Suppl 4):S138–S144. doi: 10.1097/00005344-198608004-00032. [DOI] [PubMed] [Google Scholar]
  24. Slutsky R., Watkins J., Costello D. Radionuclide evaluation of the systolic blood pressure/end-systolic volume relationship: response to pharmacologic agents in patients with coronary artery disease. Am Heart J. 1983 Jan;105(1):53–59. doi: 10.1016/0002-8703(83)90278-8. [DOI] [PubMed] [Google Scholar]
  25. Sorensen M. B., Bille-Brahe N. E., Engell H. C. Cardiac output measurement by thermal dilution: reproducibility and comparison with the dye-dilution technique. Ann Surg. 1976 Jan;183(1):67–72. doi: 10.1097/00000658-197601000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Steele P. P., Maddoux G., Kirch D. L., Vogel R. A. Effects of propranolol and nitroglycerin on left ventricular performance in patients with coronary arterial disease. Chest. 1978 Jan;73(1):19–23. doi: 10.1378/chest.73.1.19. [DOI] [PubMed] [Google Scholar]
  27. Strashun A., Horowitz S. F., Goldsmith S. J., Teichholz L. E., Dicker A., Miceli K., Gorlin R. Noninvasive detection of left ventricular dysfunction with a portable electrocardiographic gated scintillation probe device. Am J Cardiol. 1981 Mar;47(3):610–617. doi: 10.1016/0002-9149(81)90545-2. [DOI] [PubMed] [Google Scholar]
  28. Svendsen T. L., Hartling O. J., Trap-Jensen J., McNair A., Bliddal J. Adrenergic beta receptor blockade: hemodynamic importance of intrinsic sympathomimetic activity at rest. Clin Pharmacol Ther. 1981 Jun;29(6):711–718. doi: 10.1038/clpt.1981.100. [DOI] [PubMed] [Google Scholar]
  29. Svendsen T. L., Hartling O., Trap-Jensen J. Immediate haemodynamic effects of propranolol, practolol, pindolol, atenolol and ICI 89,406 in healthy volunteers. Eur J Clin Pharmacol. 1979 May 21;15(4):223–228. doi: 10.1007/BF00618509. [DOI] [PubMed] [Google Scholar]
  30. Taylor S. H., Silke B., Lee P. S., Hilal A. Haemodynamic dose-response effects of intravenous beta-blocking drugs with different ancillary properties in patients with coronary heart disease. Eur Heart J. 1982 Dec;3(6):564–569. doi: 10.1093/oxfordjournals.eurheartj.a061353. [DOI] [PubMed] [Google Scholar]
  31. Thadani U., Davidson C., Singleton W., Taylor S. H. Comparison of the immediate effects of five beta-adrenoreceptor-blocking drugs with different ancillary properties in angina pectoris. N Engl J Med. 1979 Apr 5;300(14):750–755. doi: 10.1056/NEJM197904053001402. [DOI] [PubMed] [Google Scholar]
  32. Wagner H. N., Wake R., Nickoloff E., Natarajan T. K. The nuclear stethoscope: a simple device for generation of left ventricular volume curves. Am J Cardiol. 1976 Nov 23;38(6):747–750. doi: 10.1016/0002-9149(76)90352-0. [DOI] [PubMed] [Google Scholar]
  33. Wiener L., Dwyer E. M., Jr, Cox J. W. Left ventricular hemodynamics in exercise-induced angina pectoris. Circulation. 1968 Aug;38(2):240–249. doi: 10.1161/01.cir.38.2.240. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES