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Enoximone: True inotropic effects? Do they cause ischemia? Analysis of end-systolic pressure-volume relations using the conductance (volume) Catheter technique

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Summary

True positive inotropy of enoximone is hard to prove clinically. It could increase the risk of myocardial ischemia when used in coronary artery disease (CAD). The analysis of the end-systolic pressure-volume relationship (ESPVR) as a load-independent parameter of the contractile left ventricular function (VLF) allows for differentiation of enoximone's unloading effects. Therefore, we analyzed ESPVR and LVF in 12 of 18 CAD patients before and after enoximone, 0.75 mg/kg intravenously. The slope k increased (seven patients) and loops of the ESPVR (12 patients) moved leftward with the enoximone an average of 32% and downward 19% in the diastolic portion. The delta percent changes in enoximone versus control (18 patients) indicated an improved LVF via load changes: LV filling pressure fell by 50% and end-systolic volume by 28%, while dp/dt max rose by 25%, LV work by 10% and ejection fraction by 11%. Lastly, the pacing-induced myocardial ischemia thershold increased from an average of 58±18 sec to 89±12 sec after enoximone, while ischemic postaacing LV filling pressure and ST-segment changes normalized under the drug's influence. Thus, enoximone improved LVF, both by unloading and by true positive inotropy. Lack of enoximone-induced angina and an increased anginal threshold indicate that the drug can be used safely in CAD patients as well.

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References

  1. Kereiakes D, Chatterjee K, Parmley WW, et al. Intravenous and oral MDL 17043 (a new inotropic-vasodilator agent) in congestive heart failure: Hemodynamic and clinical evaluation in 38 patients.Am J Coll Cardiol 1984;4:884–889.

    Google Scholar 

  2. Uretsky BF, Generalovich T, Reddy PS, et al. The acute hemodynamic effects of a new agent MDL 17043, in the treatment of congestive heart failure.Circulation 1983;67:823–828.

    PubMed  Google Scholar 

  3. Thormann J, Kramer W, Kindler M, et al. Dynamic pressure/volume loop analysis during acute amrinone effects in impaired LV-function: Computer-assisted LV-volume registration by conductance catheter. Xth World Congress of Cardiology, Washington DC, 1986:1298.

  4. Baim DS, McDowell AV, Cheniles J. Evaluation of a new bipyridine inotropic agent—milrinone—in patients with severe congestive heart failure.N Engl J Med 1983;309:748–756.

    PubMed  Google Scholar 

  5. Wilmshurst PT, Thompson DS, Suhl SM, et al. Comparison of the effects of amrinone and sodium nitroprusside on hemodynamics, contractility, and myocardial metabolism in patients with cardiac failure due to coronary artery disease and dilated cardiomyopathy.Br Heart J 1984;52:38–48.

    PubMed  Google Scholar 

  6. Jaski BE, Fifer MA, Wright RF, et al. Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure.J Clin Invest 1985;75:643–649.

    PubMed  Google Scholar 

  7. Amin DK, Shah PK, Hulse S, Shellock F. Comparative acute hemodynamic effects of intravenous sodium nitroprusside and MDL 17043, a new inotropic drug with vasodilator effects, in refractory congestive heart failure.Am Heart J 1985;109:1006–1012.

    PubMed  Google Scholar 

  8. Benotti JR, Grossman W, Braunwald E, et al. Hemodynamic assessment of amrinone: A new inotropic agent.N Engl J Med 1978;299:1373–1377.

    PubMed  Google Scholar 

  9. Crawford MH, Richards KL, Sodums MT, Kennedy GT. Positive inotropic and vasodilator effects of MDL 17043 in patients with reduced left ventricular performance.Am J Cardiol 1984;53:1051–1053.

    PubMed  Google Scholar 

  10. Herrmann HC, Ruddy TD, Dec W, et al. Inotropic effect of enoximone in patients with severe heart failure: Demonstration by left ventricular endsystolic pressure-volume analysis.J Am Coll Cardiol 1987;9:1117–1123.

    PubMed  Google Scholar 

  11. Wilmshurst PT, Thompson DS, Jenkins BS, et al. Hemodynamic effects of intravenous amrinone in patients with impaired left ventricular function.Br Heart J 1983;49:77–82.

    PubMed  Google Scholar 

  12. Hermiller JB, Leithe ME, Magorien RD, et al. Amrinone in severe congestive heart failure: Another look at an intriguing new cardioactive drug.J Pharmac Exp Ther 1984;228:319–326.

    Google Scholar 

  13. Sagawa K., Endsystolic pressure-volume relationship in retrospect and prospect.Fed Proc 1984;43:2399–2409.

    PubMed  Google Scholar 

  14. Suga H, Sagawa K. Instantaneous pressure volume relationships and their ratio in the excised, supported canine left ventricle.Circ Res 1974;35:117–123.

    PubMed  Google Scholar 

  15. Kass DA, Midei M, Graves W. Use of conductance (volume) catheter and transient inferior vena caval occlusion for rapid determination of pressure-volume relationships in man.Cath Cardiovasc Diag 1988;15:192–202.

    Google Scholar 

  16. Baan J, Van de Velde ET, DeBruin HG, et al. Continuous measurement of left ventricular volume in animals and humans by conductance catheter.Circulation 1984;70:812–823.

    PubMed  Google Scholar 

  17. Thormann J, Kramer W, Kindler M, et al. Bestimmung der wirkkomponenten von amrinon durch kontinuierliche analyse der druck-volumenbeziehung; Anwendung der conductance-(volumen-) kathetertechnik und der schnellen laständerung durch ballonokklusion der vena cava inferior.Z Kardiol 1987;76:530–540.

    PubMed  Google Scholar 

  18. Thormann J, Hüting J, Kremer P, et al. Do class 1 antiarrhythmic drugs impair myocardial contractility? The class 1A example of ajmaline (conductance technique).J Cardiovasc Pharmacol.

  19. Bashore TM, Walker S, Fossen DV, et al. Use of inferior vena caval occlusion to acutely alter preload in man.Circulation 1985;72(Suppl III):III43.

    Google Scholar 

  20. McKay RG, Miller MJ, Ferguson JJ, et al. Assessment of left ventricular end-systolic pressure-volume relations with an impedance catheter and transient inferior vena cava occlusion: Use of this system in the evaluation of the cardiotonic effects of dobutamine, milrinone.Am J Coll Cardiol 1986;8:1152–1160.

    Google Scholar 

  21. Van Fossen D, Fontana ME, Unverferth DV, et al. Safety and efficacy of inferior vena caval occlusion to rapidly alter ventricular loading conditions in idiopathic dilated cardiomyopathy.Am J Cardiol 1987;59:937–942.

    PubMed  Google Scholar 

  22. Baller D, Bretschneider HJ, Hellige G. A critical look at currently used indirect indices of myocardial oxygen consumption.Basic Res Cardiol 1981;76:163–181.

    PubMed  Google Scholar 

  23. Schaper W. Determinants of myocardial oxygen consumption and coronary blood flow. In: Schaper W, ed.The pathophysiology of myocardial perfusion. Amsterdam: Elsevier/North-Holland Biomedical Press, 1979; 173–176.

    Google Scholar 

  24. Thormann J, Kremer P, Mitrovic V, et al. Effects of enoximone in coronary artery disease: Increased pump function. improved ventricular wall motion, and abolition of pacing-induced myocardial ischemia.J Appl Cardiol 1989;4:31–45.

    Google Scholar 

  25. White DH, Crawford MH, O'Rourke RA. Beneficial effects of prolonged low dose dopamine in hospitalized patients with severe refractory heart failure.Clin Cardiol 1979;2:135–159.

    PubMed  Google Scholar 

  26. Thompson DS, Juul SM, Wilmshurst P. Effects of sodium nitroprusside upon cardiac work, efficiency and substrate extraction in severe left ventricular failure.Br Heart J 1981;46:394–400.

    PubMed  Google Scholar 

  27. Strain J, Grose R, Maskin CS, LeJemtel TH. Effects of a new cardiotonic agent, MDL 17043 on myocardial contractility and left ventricular performance in congestive heart failure.Am Heart J 1985;110:91–96.

    PubMed  Google Scholar 

  28. Quinones MA, Gaasch WH, Alexander JK. Influence of acute changes in preload, afterload, contractile state and heart rate on ejection and isovolumetric indices of myocardial contractility in man.Circulation 1976;53:293–302.

    PubMed  Google Scholar 

  29. Mason DT. Usefulness and limitations of the rate of rise of intraventricular pressure (dP/dt) in the evaluation of myocardial contractility in man.Am J Cardiol 1969;23:516–527.

    PubMed  Google Scholar 

  30. Ludmer PL, Wright RF, Arnold MO, et al. Separation of the direct myocardial and vasodilator actions of milrinone administered by an intracoronary infusion technique.Circulation 1986;73:130–137.

    PubMed  Google Scholar 

  31. Cody RJ, Kubo SH, Covit AB. Regional blood flow and neurohumoral responses to chronic milrinone in CHF.Circulation 1984;70:II192.

    Google Scholar 

  32. Bristow MR, Ginsburg R, Minobe W, Decreased catecholamine sensitivity and beta-adrenegric receptor density in failing human hearts.N Engl J Med 1982;307:205–211.

    PubMed  Google Scholar 

  33. Sagawa K. The ventricular pressure-volume diagram revisited.Circ Res 1978;43:677–687.

    PubMed  Google Scholar 

  34. Thormann J, Kramer W, Kindler M, et al. Linksventrikuläre funktionsdiagnostik mit analyse serieller druckvolumenbeziehungen: Erster Einsatz der conductance (volumen-)kathetertechnik.Z Kardiol 1985;74(Suppl 5):124.

    Google Scholar 

  35. Burkhoff D, Van der Velde ET, Kass D, et al. Accuracy of volume measurements by conductance catheter in isolated, ejecting canine hearts.Circulation 1985;72:440–447.

    PubMed  Google Scholar 

  36. Boltwood CM, Appleyard RF, Glantz SA. Left ventricular volume measurement by conductance catheter in intact dogs. Parallel conductance volume depends on left ventricular size.Circulation 1989;80:1360–1377.

    PubMed  Google Scholar 

  37. Leatherman GF, Shook TL, Leatherman SM, Colucci WS. Use of a conductance catheter to detect increased left ventricular inotropic state by end-systolic pressure-volume analysis.Basic Res Cardiol 1989;84(Suppl 1):247–256.

    Google Scholar 

  38. Kass DA, Maugham WL. From “E max” to pressure-volume relations: A broader view.Circulation 1988;77:1203–1212.

    PubMed  Google Scholar 

  39. Aroney CN, Herrmann HC, Semigran MJ, et al. Linearity of left ventricular end-systolic pressure-volume relation in patients with severe heart failure.J Am Coll Cardiol 1989;14:127–134.

    PubMed  Google Scholar 

  40. Crotogini AJ, Willshaw P, Barra JG, et al. Inconsistency of the slope and the volume intercept of the end-systolic pressure-volume relationship as individual indexes of inotropic state in conscious dogs: Presentation of an index combining both variables.Circulation 1987;76:1115–1126.

    PubMed  Google Scholar 

  41. Mirsky I, Tajimi T, Peterson KL. The development of the entire endsystolic pressure-volume and ejection fraction—afterload relations: A new concept of systolic myocardial stiffness.Circulation 1987;76:343–356.

    PubMed  Google Scholar 

  42. Burkhoff D, Sugiura S, Yue DT, Sagawa K. Contractility-dependent curvilinearity of endsystolic pressure-volume relations.Am J Physiol 1987;252:H1218–127.

    PubMed  Google Scholar 

  43. Spartt JA, Tyson GS, Glower DD. The end-systolic pressure-volume relationship in conscious dogs.Circulation 1987;75:1295–1302.

    PubMed  Google Scholar 

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Thormann, J., Hueting, J., Kremer, P. et al. Enoximone: True inotropic effects? Do they cause ischemia? Analysis of end-systolic pressure-volume relations using the conductance (volume) Catheter technique. Cardiovasc Drug Ther 4, 1403–1415 (1990). https://doi.org/10.1007/BF02018269

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