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. 1976 Aug;58(2):312–319. doi: 10.1172/JCI108474

Effects of ouabain on myocardial oxygen supply and demand in patients with chronic coronary artery disease. A hemodynamic, volumetric, and metabolic study in patients without heart failure.

H DeMots, S H Rahimtoola, E L Kremkau, W Bennett, D Mahler
PMCID: PMC333185  PMID: 783197

Abstract

The effects of digitalis glycosides on myocardial oxygen supply and demand are of particular interest in the presence of obstructive coronary artery disease, but have not been measured previously in man. We assessed the effects of ouabain (0.015 mg/kg body weight) on hemodynamic, volumetric, and metabolic parameters in 11 patients with severe chronic coronary artery disease without clinical congestive heart failure. Because the protocol was long and involved interventions which might affect the determinations, we also studied in nine patients using an identical protocol except that ouabain administration was omitted. Left ventricular end-diastolic pressure and left ventricular end-diastolic volume fell in each patient given ouabain, even though they were initially elevated in only two patients. Left ventricular end-diastolic pressure fell from 11.5+/-1.4 (mean+/-SE) to 5.6+/-0.9 mm Hg (P less than 0.001) and left ventricular end-diastolic volume fell from 100+/-17 to 82+/-12 ml/m2 (P less than 0.01) 1 h after ouabain infusion was completed. The maximum velocity of contractile element shortening increased from 1.68+/-0.11 ml/s to 2.18+/-0.21 muscle-lengths/s (P less than 0.05) and is consistent with an increase in contractility. No significant change in these parameters occurred in the control patients. No significant change in myocardial oxygen consumption occurred after ouabain administration but this may be related to a greater decrease in mean arterial pressure in the ouabain patients than in the control patients. We conclude that in patients with chronic coronary artery disease who are not in clinical congestive heart failure left ventricular end-diastolic volume falls after ouabain administration even when it is initially normal. Though this fall would be associated with a decrease in wall tension, and, therefore, of myocardial oxygen consumption, it may not be of sufficient magnitude to prevent a net increase in myocardial oxygen consumption. Nevertheless, compensatory mechanisms prevent a deterioration of resting myocardial metabolism.

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Selected References

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  1. BROWN R., RAHIMTOOLA S. H., DAVIS G. D., SWAN H. J. THE EFFECT OF ANGIOCARDIOGRAPHIC CONTRAST MEDIUM ON CIRCULATORY DYNAMICS IN MAN. CARDIAC OUTPUT DURING ANGIOCARDIOGRAPHY. Circulation. 1965 Feb;31:234–240. doi: 10.1161/01.cir.31.2.234. [DOI] [PubMed] [Google Scholar]
  2. BRUNS F. H., HORN H. D. Quantitative Bestimmung von L(+)-Milchsäure mit Milchsäuredehydrogenase. Biochim Biophys Acta. 1956 Aug;21(2):378–380. doi: 10.1016/0006-3002(56)90023-3. [DOI] [PubMed] [Google Scholar]
  3. Braunwald E., Bloodwell R. D., Goldberg L. I., Morrow A. G. STUDIES ON DIGITALIS. IV. OBSERVATIONS IN MAN ON THE EFFECTS OF DIGITALIS PREPARATIONS ON THE CONTRACTILITY OF THE NON-FAILING HEART AND ON TOTAL VASCULAR RESISTANCE. J Clin Invest. 1961 Jan;40(1):52–59. doi: 10.1172/JCI104236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bristow J. D., Porter G. A., Kloster F. E., Griswold H. E. Hemodynamic changes attending angiocardiography. Radiology. 1967 May;88(5):939–949. doi: 10.1148/88.5.939. [DOI] [PubMed] [Google Scholar]
  5. Chaitman B. R., DeMots H., Bristow J. D., Rösch J., Rahimtoola S. H. Objective and subjective analysis of left ventricular angiograms. Circulation. 1975 Sep;52(3):420–425. doi: 10.1161/01.cir.52.3.420. [DOI] [PubMed] [Google Scholar]
  6. Coleman H. N., Sonnenblick E. H., Braunwald E. Myocardial oxygen consumption associated with external work: the Fenn effect. Am J Physiol. 1969 Jul;217(1):291–296. doi: 10.1152/ajplegacy.1969.217.1.291. [DOI] [PubMed] [Google Scholar]
  7. Covell J. W., Braunwald E., Ross J., Jr, Sonnenblick E. H. Studies on digitalis. XVI. Effects on myocardial oxygen consumption. J Clin Invest. 1966 Oct;45(10):1535–1542. doi: 10.1172/JCI105460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dodge H. T., Sandler H., Baxley W. A., Hawley R. R. Usefulness and limitations of radiographic methods for determining left ventricular volume. Am J Cardiol. 1966 Jul;18(1):10–24. doi: 10.1016/0002-9149(66)90191-3. [DOI] [PubMed] [Google Scholar]
  9. Falsetti H. L., Mates R. E., Greene D. G., Bunnell I. L. Vmax as an index of contractile state in man. Circulation. 1971 Apr;43(4):467–479. doi: 10.1161/01.cir.43.4.467. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Greene D. G., Carlisle R., Grant C., Bunnell I. L. Estimation of left ventricular volume by one-plane cineangiography. Circulation. 1967 Jan;35(1):61–69. doi: 10.1161/01.cir.35.1.61. [DOI] [PubMed] [Google Scholar]
  12. Grunkemeier G. L., Burg B. S., Anderson R. P., Rahimtoola S. H. A simple method for calculating Vmax. J Lab Clin Med. 1974 Aug;84(2):235–240. [PubMed] [Google Scholar]
  13. Hattenhaur M., Neill W. A. The effect of cold air inhalation on again pectoris and myocardial oxygen supply. Circulation. 1975 Jun;51(6):1053–1058. doi: 10.1161/01.cir.51.6.1053. [DOI] [PubMed] [Google Scholar]
  14. Hugenholtz P. G., Ellison R. C., Urschel C. W., Mirsky I., Sonnenblick E. H. Myocardial force-velocity relationships in clinical heart disease. Circulation. 1970 Feb;41(2):191–202. doi: 10.1161/01.cir.41.2.191. [DOI] [PubMed] [Google Scholar]
  15. KAHLER R. L., THOMPSON R. H., BUSKIRK E. R., FRYE R. L., BRAUNWALD E. Studies on digitalis. VI. Reduction of the oxygen debt after exercise with digoxin in cardiac patients without heart failure. Circulation. 1963 Mar;27:397–405. doi: 10.1161/01.cir.27.3.397. [DOI] [PubMed] [Google Scholar]
  16. KRASNOW N., NEILL W. A., MESSER J. V., GORLIN R. Myocardial lactate and pyruvate metabolism. J Clin Invest. 1962 Nov;41:2075–2085. doi: 10.1172/JCI104665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Klocke F. J., Bunnell I. L., Greene D. G., Wittenberg S. M., Visco J. P. Average coronary blood flow per unit weight of left ventricle in patients with and without coronary artery disease. Circulation. 1974 Sep;50(3):547–559. doi: 10.1161/01.cir.50.3.547. [DOI] [PubMed] [Google Scholar]
  18. Klocke F. J., Wittenberg S. M. Heterogeneity of coronary blood flow in human coronary artery disease and experimental myocardial infarction. Am J Cardiol. 1969 Dec;24(6):782–790. doi: 10.1016/0002-9149(69)90467-6. [DOI] [PubMed] [Google Scholar]
  19. Kloster F. E., Bristow J. D., Porter G. A., Judkins M. P., Griswold H. E. Comparative hemodynamic effects of equiosmolar injections of angiographic contrast materials. Invest Radiol. 1967 Sep-Oct;2(5):353–359. doi: 10.1097/00004424-196709000-00016. [DOI] [PubMed] [Google Scholar]
  20. Knopp T. J., Rahimtoola S. H., Swan H. J. First derivative of ventricular pressure recorded by means of conventional cardiac catheters. Cardiovasc Res. 1970 Jul;4(3):398–404. doi: 10.1093/cvr/4.3.398. [DOI] [PubMed] [Google Scholar]
  21. Leighton R. F., Wilt S. M., Lewis R. P. Detection of hypokinesis by a quantitative analysis of left ventricular cineangiograms. Circulation. 1974 Jul;50(1):121–127. doi: 10.1161/01.cir.50.1.121. [DOI] [PubMed] [Google Scholar]
  22. Love W. D., Munford R. S., Abraham R. E. Comparison of the effects of 1-norepinephrine, angiotensin, dipyridamole, digitoxin, and reserpine on the regional distribution of coronary blood flow. J Lab Clin Med. 1965 Sep;66(3):423–432. [PubMed] [Google Scholar]
  23. MASON D. T., BRAUNWALD E. STUDIES ON DIGITALIS. X. EFFECTS OF OUABAIN ON FOREARM VASCULAR RESISTANCE AND VENOUS TONE IN NORMAL SUBJECTS AND IN PATIENTS IN HEART FAILURE. J Clin Invest. 1964 Mar;43:532–543. doi: 10.1172/JCI104939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mason D. T., Braunwald E. STUDIES ON DIGITALIS. IX. EFFECTS OF OUABAIN ON THE NONFAILING HUMAN HEART. J Clin Invest. 1963 Jul;42(7):1105–1111. doi: 10.1172/JCI104796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mason D. T., Spann J. F., Jr, Zelis R. Quantification of the contractile state of the intact human heart. Maximal velocity of contractile element shortening determined by the instantaneous relation between the rate of pressure rise and pressure in the left ventricle during isovolumic systole. Am J Cardiol. 1970 Sep;26(3):248–257. doi: 10.1016/0002-9149(70)90791-5. [DOI] [PubMed] [Google Scholar]
  26. Neill W. A., Kremkau E. L. Criteria for detecting ischemic myocardial hypoxia from lactate and pyruvate data during atrial pacing in humans. J Lab Clin Med. 1974 Mar;83(3):428–435. [PubMed] [Google Scholar]
  27. Rahimtoola S. H., DiGilio M. M., Sinno M. Z., Loeb H. S., Rosen K. M., Gunnar R. M. Effects of ouabain on impaired left ventricular function during convalescence after acute myocardial infarction. Circulation. 1971 Nov;44(5):866–876. doi: 10.1161/01.cir.44.5.866. [DOI] [PubMed] [Google Scholar]
  28. Rahimtoola S. H., Duffy J. P., Swan H. C. Ventricular performance after angiocardiography. Circulation. 1967 Jan;35(1):70–78. doi: 10.1161/01.cir.35.1.70. [DOI] [PubMed] [Google Scholar]
  29. Rahimtoola S. H., Sinno M. Z., Chuquimia R., Loeb H. S., Rosen K. M., Gunnar R. M. Effects of ouabain on impaired left ventricular function in acute myocardial infarction. N Engl J Med. 1972 Sep 14;287(11):527–531. doi: 10.1056/NEJM197209142871102. [DOI] [PubMed] [Google Scholar]
  30. Severinghaus J. W. Blood gas calculator. J Appl Physiol. 1966 May;21(3):1108–1116. doi: 10.1152/jappl.1966.21.3.1108. [DOI] [PubMed] [Google Scholar]

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