Left ventricular function after oral milrinone in patients with congestive heart failure. A hemodynamic and angiographic study

  • F. Piscione
  • Patrick W. Serruys
  • P. G. Hugenholtz
Conference paper


The diastolic properties of the left ventricle (LV) are important determinants of cardiac function; alteration in diastolic function accounts for many of the clinical manifestations of congestive heart failure. Changes in myocardial relaxation and filling phases, changes in coronary blood flow, diastolic tone and ventricular shape all contribute to the abnormal diastolic compliance of the failing heart. To assess the short-term effects of a single oral dose (10 mg) of milrinone (M) on diastolic function, 14 patients (pts), mean age 59 ± 6 years, with severe congestive heart failure underwent this study. After baseline hemodynamic measurements, LV angiography with simultaneous recording of LV pressure (tip-manometry) and pressure-derived parameters was performed at paced heart rate (15 beats above spontaneous heart rate). After repeat baseline measurements, M was administered followed by LV pressure measurements at 10′ intervals to 50′ together with coronary blood flow measurement. Blood samples to determine the plasma concentration of M were withdrawn at the same intervals. Blood arterial and coronary sinus samples for catecholamine levels and oxygen saturations were withdrawn before and 50′ after M. LV angiography was repeated 60′ after M at matched atrial paced rates with simultaneous pressure recordings. During the first phase of the study, peak negative dP/dt progressively and significantly increased from 827 ± 209 to 904 ± 194mm Hg/sec (p < 0.01) whereas LV systolic pressure slightly decreased. The time constant of early relaxation, Tau1,(fit for the first 40 msec. after the occurrence of peak negative dP/dt), decreased progressively and significantly from 71 ± 17 to 58 ± 14 msec (p < 0.01). Minimal LV diastolic pressure and LV end-diastolic pressure (LVEDP) were significantly lowered after 50′ from 13 ± 4 to 10 ± 7 mm Hg (p < 0.05) and from 27 ± 7 to 20 ± 10 mm Hg (p < 0.01), respectively. Coronary blood flow rose progressively during the first 40′ but the increase failed to be significant at 50′. Coronary vascular resistance reciprocated these changes. Myocardial oxygen consumption remained unchanged over 50′. Noradrenaline, adrenaline and dopamine mean values also remained unchanged over 50′, thus demonstrating a lack of effect of M on the basal, elevated sympathetic tone. Mean plasma level of M rose progressively, achieving a therapeutic level after 30′. The analysis of LV volume, pressure and pressure-derived parameters during angiography showed an improved relaxation phase with an increase in peak filling rate from 290 ± 27 to 338 ± 55 ml sec. The constant of elastic chamber stiffness, measured by the simple elastic model, decreased but not significantly. Pressure-volume loops showed a downward shift in 10/14 pts, mainly because of a major reduction in LVEDP from 29 ± 10 to 20 ± 11 mm Hg (p < 0.001) while end-diastolic volume only slightly decreased.

Conclusion: improvement in parameters of LV diastolic relaxation and filling with changes in chamber distensibility following oral M, suggest that improved diastolic function may contribute to the beneficial effects of M on the failing heart.

During the last two years several investigators have demonstrated that the administration of milrinone in patients with congestive heart failure leads to an increased inotropism together with a vasodilation, in absence or with only slight changes in heart rate and aortic pressure (1, 7, 10, 16). Recently an improvement in diastolic left ventricular performance, occurring after intravenous milrinone, has been reported (14). In the present study we evaluated the effect of a single oral dose of milrinone on central hemodynamics and on systolic and diastolic mechanics in patients with congestive heart failure.


Severe Congestive Heart Failure Peak Filling Rate Peak Ejection Rate Oral Milrinone Left Ventricle Systolic Pressure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Baim DS, McDowell AV, Cherniler J, Monard E, Parker JA, Edelwon J, Braunwald E, Grossmann W (1983) Evaluation of a new bipyridine inotropic agent — milrinone — in patients with severe congestive heart failure. New Engl J Med 309: 749 – 756CrossRefGoogle Scholar
  2. 2.
    Borow KM, Come PC, Neumann A, Baims DS, Braunwald E, Grossmann W (1985) Physiologic assessment of the inotropic, vasodilator and afterload reducing effects of milrinone in subjects without cardiac disease. Am J Cardiol 55: 1204 – 1209PubMedCrossRefGoogle Scholar
  3. 3.
    Brower RW, Meij S, Serruys PW (1983) A model of asynchronous left ventricular relaxation predicting the bi-exponential pressure decay. Cardiovasc Res 17: 482 – 488PubMedCrossRefGoogle Scholar
  4. 4.
    Edelson J, Koss RF, Baker JF, Park GO (1983) High performance liquid chromatographic analysis of WIN 47.203 in plasma and urine. Intravenous pharmacokinetics in the dog. Chromatogr F276: 456–462Google Scholar
  5. 5.
    Grossmann W, Haynes F, Paraskos JA, Saltz S, Dalen JE, Dexter LE (1972) Alterations in preload and myocardial mechanics in the dog and in man. Circ Res 31: 83 – 94CrossRefGoogle Scholar
  6. 6.
    Gwethmey JK, De Feo TT, Morgan JP (1984) The effects of milrinone and 2H-imidazol-2-one, 4ethyl-1,3-didydro-5-(4-pyridimilcarbonil)-(MDL 19.205) on intracellular calcium transients in mammalian working myocardium. Fed Proc 43: 768 (abstr)Google Scholar
  7. 7.
    Jaski BE, Fifer MA, Wright RF, Braunwald E, Colucci WS (1985) Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside. J Clin Invest 75: 643–649Google Scholar
  8. 8.
    Mahler F, Yoran C, Ross J Jr (1974) Inotropic effect of tachycardia and post-stimulation potentiation in the conscious dog. Am J Physiol 227: 569 – 575PubMedGoogle Scholar
  9. 9.
    Mahler F, Ross J Jr, O’Rourke RA, Covell JW (1975) Effects of changes in preload, afterload and inotropic state on ejection and isovolumic phase measures of contractility in the conscious dog. Am J Cardiol 35: 626 – 634PubMedCrossRefGoogle Scholar
  10. 10.
    Maskin CS, Sinoway L, Chadwick B, Sonnenblick EH, Le Jemtel TH (1983) Sustained hemodynamic and clinical effects of a new cardiotonic agent, WIN 47203, in patients with severe congestive heart failure. Circulation 67: 1065 – 1070PubMedCrossRefGoogle Scholar
  11. 11.
    Meester GT, Bernard N, Zeelenberg C, Brower RW, Hugenholtz PG (1975) A computer system for real time analysis of cardiac catheterization data. Cathet Cardiovasc Diagno 1: 112 – 132Google Scholar
  12. 12.
    Rude RE, Grossmann W, Colucci WS, Benotti JR, Carabello BA, Wynne J, Malacoff R, Braunwald E (1981) Problems in assessment of new pharmacologic agents for the heart failure patient. Am Heart J 102: 584 – 590PubMedCrossRefGoogle Scholar
  13. 13.
    Sabbah HN, Stein PD (1981) Effect of inotropic interventions on rate of change of ventricular diastolic dimensions. Am J Physiol 241: H376 – 380PubMedGoogle Scholar
  14. 14.
    Scott Monrad E, MacKay RG, Baim DS, Colucci WS, Fifer MA, Heller CV, Royal HD, Grossmann W (1984) Improvements in indexes of diastolic performance in patients with congestive heart failure treated with milrinone. Circulation 70: 1030 – 1037CrossRefGoogle Scholar
  15. 15.
    Serruys PW, Wijns W, van den Brand M, Meij S, Slager CJ, Schuurbiers JCH, Hugenholtz PG, Brower RW (1984) Left ventricular performance, regional blood flow, wall motion and lactate metabolism during transluminal angioplasty. Circulation 70: 25 – 36PubMedCrossRefGoogle Scholar
  16. 16.
    Simonton C, Chatterjee K, Cooly RJ, Kubo SH, Leonard D, Daly P, Rutman H (1985) Milrinone in congestive heart failure: acute and chronic hemodynamic and clinical evaluation. J Am Coll Cardiol 6: 453 – 459PubMedCrossRefGoogle Scholar
  17. 17.
    Slager CJ, Reiber JHC, Schuurbiers JCH, Meester GT (1978) Contouromat, a hardwired left ventricular angio processing system. Design and application. Comput Biomed Res 11: 491–502Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • F. Piscione
    • 1
  • Patrick W. Serruys
    • 1
    • 2
  • P. G. Hugenholtz
    • 1
  1. 1.The Catheterization Laboratory, ThoraxcenterErasmus UniversityRotterdamThe Netherlands
  2. 2.Catheterization Laboratory, ThoraxcenterRotterdamThe Netherlands

Personalised recommendations