Skip to main content
NCBI home page
British Heart Journal logoLink to British Heart Journal
. 1980 Jun;43(6):668–679. doi: 10.1136/hrt.43.6.668

Haemodynamic and metabolic effects of atenolol in patients with angina pectoris.

D S Thompson, N Naqvi, S M Juul, D J Coltart, B S Jenkins, M M Webb-Peploe
PMCID: PMC482768  PMID: 7426146

Abstract

Myocardial substrate extraction, coronary sinus flow, left ventricular pressure, and cardiac output were measured in 11 patients with angina pectoris at three pacing rates before and after atenolol (0.2 mg/kg). Left ventricular pressures, and the product of systolic pressure time index and heart rate did not change, but max dP/dt and KV max fell after atenolol. Only at the lowest pacing rate did the drug reduce cardiac output. Coronary sinus blood flow and myocardial oxygen uptake did not change after atenolol. At the highest pacing rate before atenolol four patients developed angina, accompanied by a rise in end-diastolic pressure. After atenolol angina was abolished in three, but the end-diastolic pressure still rose at the highest pacing rate. Myocardial lactate extraction ratio fell as heart rate increased, and was lower in the patients who developed angina. After atenolol, lactate extraction ratio increased significantly at the highest and lowest pacing rates. Myocardial pyruvate extraction rose after the drug. Arterial concentrations of hydroxybutyrate and acetoacetate fell after atenolol, but the decrease in their extraction was not significant. Myocardial extraction of free fatty acids was related to arterial concentration, which fell after atenolol. The changes in lactate and pyruvate extraction after atenolol were related inversely to changes in arterial free fatty acid concentration suggesting that the improvement in myocardial metabolism could have been secondary to reduced peripheral lipolysis. The increase in lactate extraction was associated with relief of angina, but did not abolish the rise in end-diastolic pressure induced by pacing.

Full text

PDF
668

Selected References

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

  1. BASSENGE E., WENDT V. E., SCHOLLMEYER P., BLUEMCHEN G., GUDBJARNASON S., BING R. J. EFFECT OF KETONE BODIES ON CARDIAC METABOLISM. Am J Physiol. 1965 Jan;208:162–168. doi: 10.1152/ajplegacy.1965.208.1.162. [DOI] [PubMed] [Google Scholar]
  2. BING R. J. CARDIAC METABOLISM. Physiol Rev. 1965 Apr;45:171–213. doi: 10.1152/physrev.1965.45.2.171. [DOI] [PubMed] [Google Scholar]
  3. Barrett A. M. The pharmacology of atenolol. Postgrad Med J. 1977;53 (Suppl 3):58–64. [PubMed] [Google Scholar]
  4. Barry W. H., Brooker J. Z., Alderman E. L., Harrison D. C. Changes in diastolic stiffness and tone of the left ventricle during angina pectoris. Circulation. 1974 Feb;49(2):255–263. doi: 10.1161/01.cir.49.2.255. [DOI] [PubMed] [Google Scholar]
  5. Braunwald E. Control of myocardial oxygen consumption: physiologic and clinical considerations. Am J Cardiol. 1971 Apr;27(4):416–432. doi: 10.1016/0002-9149(71)90439-5. [DOI] [PubMed] [Google Scholar]
  6. Carruthers M., Young D. A. Free fatty acid estimation by a semi-automated fluorimetric method. Clin Chim Acta. 1973 Dec 27;49(3):341–348. doi: 10.1016/0009-8981(73)90231-3. [DOI] [PubMed] [Google Scholar]
  7. Coore H. G., Denton R. M., Martin B. R., Randle P. J. Regulation of adipose tissue pyruvate dehydrogenase by insulin and other hormones. Biochem J. 1971 Nov;125(1):115–127. doi: 10.1042/bj1250115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Day J. L. The metabolic consequences of adrenergic blockade: a reveiw. Metabolism. 1975 Aug;24(8):987–996. doi: 10.1016/0026-0495(75)90090-6. [DOI] [PubMed] [Google Scholar]
  9. Deacon S. P. The effects of atenolol and propranolol upon lipolysis. Br J Clin Pharmacol. 1978 Feb;5(2):123–125. doi: 10.1111/j.1365-2125.1978.tb01611.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. GUZMAN S. V., WEST J. W. Cardiac effects of intracoronary arterial injections of various roentgenographic contrast media. Am Heart J. 1959 Oct;58:597–607. doi: 10.1016/0002-8703(59)90095-x. [DOI] [PubMed] [Google Scholar]
  11. Ganz W., Tamura K., Marcus H. S., Donoso R., Yoshida S., Swan H. J. Measurement of coronary sinus blood flow by continuous thermodilution in man. Circulation. 1971 Aug;44(2):181–195. doi: 10.1161/01.cir.44.2.181. [DOI] [PubMed] [Google Scholar]
  12. Graber J. D., Conti C. R., Lappe D. L., Ross R. S. Effect of pacing-induced tachycardia and myocardial ischemia on ventricular pressure-velocity relationships in man. Circulation. 1972 Jul;46(1):74–83. doi: 10.1161/01.cir.46.1.74. [DOI] [PubMed] [Google Scholar]
  13. Graham T. P., Jr, Covell J. W., Sonnenblick E. H., Ross J., Jr, Braunwald E. Control of myocardial oxygen consumption: relative influence of contractile state and tension development. J Clin Invest. 1968 Feb;47(2):375–385. doi: 10.1172/JCI105734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Grossman W., Brooks H., Meister S., Sherman H., Dexter L. New technique for determining instantaneous myocardial force-velocity relations in the intact heart. Circ Res. 1971 Feb;28(2):290–297. doi: 10.1161/01.res.28.2.290. [DOI] [PubMed] [Google Scholar]
  15. HOHORST H. J., KREUTZ F. H., BUECHER T. [On the metabolite content and the metabolite concentration in the liver of the rat]. Biochem Z. 1959;332:18–46. [PubMed] [Google Scholar]
  16. Jackson G., Atkinson L., Oram S. Improvement of myocardial metabolism in coronary arterial disease by beta-blockade. Br Heart J. 1977 Aug;39(8):829–833. doi: 10.1136/hrt.39.8.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jackson G., Harry J. D., Robinson C., Kitson D., Jewitt D. E. Comparison of atenolol with propranolol in the treatment of angina pectoris with special reference to once daily administration of atenolol. Br Heart J. 1978 Sep;40(9):998–1004. doi: 10.1136/hrt.40.9.998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. KORN E. D. Clearing factor, a heparin-activated lipoprotein lipase. I. Isolation and characterization of the enzyme from normal rat heart. J Biol Chem. 1955 Jul;215(1):1–14. [PubMed] [Google Scholar]
  19. Kerbey A. L., Randle P. J., Cooper R. H., Whitehouse S., Pask H. T., Denton R. M. Regulation of pyruvate dehydrogenase in rat heart. Mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: role of coenzyme A, acetyl-coenzyme A and reduced and oxidized nicotinamide-adenine dinucleotide. Biochem J. 1976 Feb 15;154(2):327–348. doi: 10.1042/bj1540327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kjekshus J. K., Mjos O. D. Effect of free fatty acids on myocardial function and metabolism in the ischemic dog heart. J Clin Invest. 1972 Jul;51(7):1767–1776. doi: 10.1172/JCI106978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kolettis M., Jenkins B. S., Webb-Peploe M. M. Assessment of left ventricular function by indices derived from aortic flow velocity. Br Heart J. 1976 Jan;38(1):18–31. doi: 10.1136/hrt.38.1.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lassers B. W., Kaijser L., Wahlqvist M. L., Carlson L. A. Relationship in man between plasma free fatty acids and myocardial metabolism of carbohydrate substrates. Lancet. 1971 Aug 28;2(7722):448–450. doi: 10.1016/s0140-6736(71)92624-9. [DOI] [PubMed] [Google Scholar]
  23. Lech J. J., Jesmok G. J., Calvert D. N. Effects of drugs and hormones on lipolysis in heart. Fed Proc. 1977 Jun;36(7):2000–2008. [PubMed] [Google Scholar]
  24. Leighton R. F., Zaron S. J., Robinson J. L., Weissler A. M. Effects of atrial pacing on left ventricular performance in patients with heart disease. Circulation. 1969 Nov;40(5):615–622. doi: 10.1161/01.cir.40.5.615. [DOI] [PubMed] [Google Scholar]
  25. Linhart J. W., Hildner F. J., Barold S. S., Listejw, Samet P. Left heart hemodynamics during angina pectoris induced by atrial pacing. Circulation. 1969 Oct;40(4):483–492. doi: 10.1161/01.cir.40.4.483. [DOI] [PubMed] [Google Scholar]
  26. Linhart J. W. Pacing-induced changes in stroke volume in the evaluation of myocardial function. Circulation. 1971 Feb;43(2):253–261. doi: 10.1161/01.cir.43.2.253. [DOI] [PubMed] [Google Scholar]
  27. Mathey D. G., Chatterjee K., Tyberg J. V., Lekven J., Brundage B., Parmley W. W. Coronary sinus reflux. A source of error in the measurement of thermodilution coronary sinus flow. Circulation. 1978 Apr;57(4):778–786. doi: 10.1161/01.cir.57.4.778. [DOI] [PubMed] [Google Scholar]
  28. Most A. S., Brachfeld N., Gorlin R., Wahren J. Free fatty acid metabolism of the human heart at rest. J Clin Invest. 1969 Jul;48(7):1177–1188. doi: 10.1172/JCI106082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. O'Brien K. P., Higgs L. M., Glancy D. L., Epstein S. E. Hemodynamic accompaniments of angina: a comparison during angina induced by exercise and by atrial pacing. Circulation. 1969 Jun;39(6):735–743. doi: 10.1161/01.cir.39.6.735. [DOI] [PubMed] [Google Scholar]
  30. Parker J. O., Khaja F., Case R. B. Analysis of left ventricular function by atrial pacing. Circulation. 1971 Feb;43(2):241–252. doi: 10.1161/01.cir.43.2.241. [DOI] [PubMed] [Google Scholar]
  31. Parker J. O., Ledwich J. R., West R. O., Case R. B. Reversible cardiac failure during angina pectrois: hemodynamic effects of atrial pacing in coronary artery disease. Circulation. 1969 Jun;39(6):745–757. doi: 10.1161/01.cir.39.6.745. [DOI] [PubMed] [Google Scholar]
  32. Rahimtoola S. H., Gau G. T., Raphael M. J. Cardiac performance after diagnostic coronary arteriography. Circulation. 1970 Mar;41(3):537–544. doi: 10.1161/01.cir.41.3.537. [DOI] [PubMed] [Google Scholar]
  33. Robinson C., Jackson G., Fisk C., Jewitt D. Haemodynamic effects of atenolol in patients with coronary artery disease. Br Heart J. 1978 Jan;40(1):22–28. doi: 10.1136/hrt.40.1.22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rutstein D. D., Castelli W. P., Nickerson R. J. Heparin and human lipid metabolism. Lancet. 1969 May 17;1(7603):1003–1008. doi: 10.1016/s0140-6736(69)91801-7. [DOI] [PubMed] [Google Scholar]
  35. SARNOFF S. J., BRAUNWALD E., WELCH G. H., Jr, CASE R. B., STAINSBY W. N., MACRUZ R. Hemodynamic determinants of oxygen consumption of the heart with special reference to the tension-time index. Am J Physiol. 1958 Jan;192(1):148–156. doi: 10.1152/ajplegacy.1957.192.1.148. [DOI] [PubMed] [Google Scholar]
  36. Schang S. J., Pepine C. J. Effects of propranolol on coronary hemodynamic and metabolic responses to tachycardia stress in patients with and without coronary disease. Cathet Cardiovasc Diagn. 1977;3(1):47–57. doi: 10.1002/ccd.1810030106. [DOI] [PubMed] [Google Scholar]
  37. Shrago E. The effect of long chain fatty acyl CoA esters on the adenine nucleotide translocase and myocardial metabolism. Life Sci. 1978 Jan;22(1):1–5. doi: 10.1016/0024-3205(78)90403-4. [DOI] [PubMed] [Google Scholar]
  38. Simonsen S. Effect of atenolol (ICI 66 082) on coronary haemodynamics in man. Br Heart J. 1977 Nov;39(11):1210–1216. doi: 10.1136/hrt.39.11.1210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. WILLIAMSON D. H., MELLANBY J., KREBS H. A. Enzymic determination of D(-)-beta-hydroxybutyric acid and acetoacetic acid in blood. Biochem J. 1962 Jan;82:90–96. doi: 10.1042/bj0820090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wolfson S., Gorlin R. Cardiovascular pharmacology of propranolol in man. Circulation. 1969 Oct;40(4):501–511. doi: 10.1161/01.cir.40.4.501. [DOI] [PubMed] [Google Scholar]
  41. Wolfson S., Heinle R. A., Herman M. V., Kemp H. G., Sullivan J. M., Gorlin R. Propranolol and angina pectoris. Am J Cardiol. 1966 Sep;18(3):345–353. doi: 10.1016/0002-9149(66)90052-x. [DOI] [PubMed] [Google Scholar]
  42. Zierler K. L. Fatty acids as substrates for heart and skeletal muscle. Circ Res. 1976 Jun;38(6):459–463. doi: 10.1161/01.res.38.6.459. [DOI] [PubMed] [Google Scholar]

Articles from British Heart Journal are provided here courtesy of BMJ Publishing Group

RESOURCES