Summary
The phosphodiesterase inhibitors have been recognised as potent inotropic and vasodilating drugs. In acute congestive heart failure they increase cardiac output, decrease left pulmonary capillary wedge pressure, and reduce total peripheral resistance with an improvement in loading conditions of the failing heart. Their potency in reversal of symptoms of acute congestive heart failure is quite similar to, or even better than, treatment with intravenous catecholamines and sodium nitroprusside. In chronic congestive heart failure, however, these agents increase mortality and have deleterious effects in the outcome of patients with severe left ventricular dysfunction.
Similar content being viewed by others
References
Alousi AA, Canter JM, Cicero F. Pharmacology of milrinone. In Braunwald E et al. (Eds) Milrinone: investigation of new inotropic therapy for congestive heart failure pp. 21–48, Raven Press, New York, 1984
Alousi AA, Canter JM, Montenaro MJ, Fort DJ, Ferrari RA. Cardiotonic activity of amrinone, a new and potent cardiac bipyridine, on the normal and failing heart of experimental animals. Journal of Cardiovascular Pharmacology 5: 792–803, 1983
Alousi AA, Farah AE, Lesher GY, Opalka Jr CJ. Cardiotonic activity of amrinone-WIN 40680. Circulation Research 45: 666–677, 1979
Alousi AA, Johnson DC. Pharmacology of the bipyridines: amrinone and milrinone. Circulation 73 (Suppl. III): III–10–24, 1986
Amin DK, Shah PK, Hulse S, Shellock FG, Swan HJC. Myocardial metabolic and hemodynamic effects of intravenous MDL 17,043, a new cardiotonic drug, in patients with chronic severe heart failure. American Heart Journal 108: 1285–1292, 1984
Amin DK, Shah PK, Hulse S, Shellock F. Comparative acute hemodyamic effects of MDL 17,043, a new inotropic drug with vasodilator effects, in refractory congestive heart failure. American Heart Journal 109: 1006–1012, 1985a
Amin DK, Shah PK, Shellock FG, Hulse S, Brandon G, Spangenberg R, Swan HJC. Comparative hemodynamic effects of intravenous dobutamine and MDL-17,043, a new cardioactive drug, in severe congestive heart failure. American Heart Journal 109: 91–99, 1985b
Anderson JL, Askins JC, Gilbert EM, Menlove RL, Lutz JR. Occurence of ventricular arrhythmias in patients receiving acute and chronic infusions of milrinone. American Heart Journal 111: 466–474, 1986
Anderson JL, Bairn DS, Fein SA, Goldstein RA, Le Jemtel TH, Likhoff MJ for the milrinone investigators and their associates. Efficacy and safety of sustained (48 hour) intravenous infusions of milrinone in patients with severe congestive heart failure: a multicenter study. Journal of the American College of Cardiology 9: 711–722, 1987
Arbogast R, Brand C, Haegele KD, Fincker JL, Schechter PJ. Hemodynamic effects of MDL 17,043, an new cardiotonic agent, in patients with congestive heart failure: comparison with nitroprusside. Journal of Cardiovascular Pharmacology 5: 998–1004, 1983
Arbogast R, Brandt CM, Finkcer JL, Schechter PJ. Acute hemodynamic effects of piroximone (MDL 19,205) in patients with moderate congestive heart failure: comparison with sodium nitroprusside. Journal of Cardiovascular Pharmacology 8: 82–89, 1986
Axelrod RJ, de Marco T, Dae M, Botvinick EH, Chaterjee K. Hemodynamic and clinical evaluation of piroximone, a new inotropevasodilator agent, in severe congestive heart failure. Journal of the American College of Cardiology 9: 1124–1130, 1987
Bairn DS, McDowell AV, Cherniles. Evaluation of a new bipyridine inotropic agent — milrinone — in patients with severe congestive heart failure. New England Journal of Medicine 309: 748–756, 1983
Bairn DS, Colucci WS, Monrad EC, Smith HS, Wright RF, et al. Survival of patients with severe congestive heart failure treated with oral milrinone. Journal of the American College of Cardiology 7: 661–670, 1986
Baumann G, Ningel K, Vieweg J, Joder-Ohlenbusch AM, Cremer G. Piroximone, dobutamine and nitroprusside: comparative effects on haemodynamics in patients with congestive heart failure. European Heart Journal 12: 533–540, 1991
Belz GG, Meinicke T, Schafer-Korting M. The Relationship between pharmacokinetics and pharmacodynamics of enoximone in healthy man. European Journal of Clinical Pharmacology 35: 631–635, 1988
Benotti JR, Lesko LJ, McCue JE. Acute pharmacodynamics and pharmacokinetics of oral amrinone. Journal of Clinical Pharmacology 22: 425–432, 1982
Benotti JR, Grossman W, Braunwald E, Davolos DD, Alousi AA. Hemodynamic assessment of amrinone: a new inotropic agent. New England Journal of Medicine 299: 1373–1377, 1978
Bethke, T, Brunkhorst D, van der Leyen H, Meyer W, Nigur R, Scholz H. Mechanisms of action and cardiotonic activity of a new phosphodiesterase inhibitor, the benzimidazole derivate adibendan (BM 14,478) in guinea-pig hearts. Naunyn-Schmiedeberg’s Archives of Pharmacology 337: 576–582, 1988
Biddle TL, Benotti JR, Creager MA, Faxon DP, Firth BG, et al. Comparison of intravenous milrinone and dobutamine for congestive heart failure secondary to either ischemic or dilated cardiomyopathy. American Journal of Cardiology 59: 1345–1350, 1987
Bleifeld WH, Storstein L. Heart failure: therapeutic challenges and strategies and the role of phosphodiesterase inhibitors. European Heart Journal 10 (Suppl. 10): 1–59, 1989
Boehm M, Morano I, Piske B, Rueg JC, Wankerl M, Zimmermann R, Erdmann E. Contribution of cAMP-phosphodiest-erase inhibition and sensitization of the contractile proteins for calcium to the inotropic effect of pimobendan in the failing human myocardium. Circulation 68: 689–701, 1991
Brown L, Lorenz B, Erdmann E. Reduced positive inotropic effects in diseased human ventricular myocardium. Cardiovascular Research 20: 516–520, 1986
Brunkhorst D, van der Leyen H, Meyer W, Nigbur R, Schmidt-Schumacher C, Scholz H. Relation of positive inotropic and chronotropic effects of pimobendan, UD-CG 212, milrinone and other phosphodiesterase inhibitors to phosphodiesterase III inhibition in guinea-pig heart. Naunyn-Schmiederberg’s Archives Pharmacology 339: 575–583, 1989
Campell CA, Mehta PM, Wynne J, Kloner RA. The cardiotonic agent amrinone does not increase anatomic infarct size. Journal of Cardiovascular Pharmacology 9: 225–229, 1987
Chapman RA. Excitation-contraction coupling in cardiac muscle. Progress in Biophysical Molecular Biology 35: 1–52, 1980
Choraria SK, Taylor D, Pilcher J. Double-blind crossover comparison of enoximone and placebo in patients with congestive heart failure. Circulation 76: 1307–1311, 1987
Cody RJ, Muller FB, Kubo SH, Rutman H, Leonard D. Identification of the direct vasodilator effect of milrinone with an isolated limb preparation in patients with chronic congestive heart failure. Circulation 73: 124–129, 1986
Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, et al. A comparison of enalapril with hydralazine — isosorbide dinitrate in the treatment of congestive heart failure. New England Journal of Medicine 325: 303–310, 1991
Coghlan JG, Norell M, Ilsley CD, Mitchell AG. Oral treatment with enoximone in patients referred for cardiac transplantation. International Journal of Cardiology 32: 57–64, 1991
Colucci WS, Wright RF, Braunwald E. New positive inotropic agents in the treatment of congestive heart failure. New England Journal of Medicine 314: 290–299, 1986
Colucci WS. Observations on the intracoronary administration of milrinone and dobutamine to patients with congestive heart failure. American Journal of Cardiology 63: 17A-22A, 1989
Crawford MH, Richards KL, Sodums MT, Kennedy GT. Positive inotropic and vasodilator effects of MDL 17,043 in patients with reduced left ventricular performance. American Journal of the College of Cardiology 53: 1051–1053, 1984
Crawford MH. Intravenous use of enoximone. American Journal of Cardiology 60: 42C-45C, 1987
Dage RC, Roebel LE, Hsieh CP, Woodward JK. Cardiovascular properties of a new cardiotonic agent, MDL 19,205. Journal of Cardiovascular Pharmacology 6: 35–42, 1984
Di Bianco R, Shabetai R, Silverman BD, Leier CY, Benotti JR with the amrinone multicenter study inverstigators. Oral amrinone for the treatment of chronic congestive heart failure: results of a multicenter randomized double blind and placebocontrolled withdrawal study. Journal of the American College of Cardiology 4: 855–866, 1984
Di Bianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R. A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. New England Journal of Medicine 320: 677–683, 1989
Dies F, Krell MJ, Whitlow P, et al. Intermittent dubutamine in ambulatory outpatients with chronic cardiac failure. Circulation 74 (Suppl. II): 11–38, 1986
Ebashi S, Endo M. Calcium ion and muscle contraction. Progress in Biophysical and Molecular Biology 18: 123–183, 1968
Eichhorn EJ, Konstam MA, Weiland DS, Roberts DJ, Martin TT, et al. Differential effects of milrinone and dobutamine on right ventricular preload, afterload and systolic performance in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. American Journal of Cardiology 60: 1329–1333, 1987
Erbel R, Meyer J, Diefenbach C, Delorme G, Bourdarias JP, et al. A dose response study of intravenous enoximone in congestive heart failure. American Journal of Cardiology 59: 31C-36C, 1987
Erhard PW, Hagedorn AA, Sabio M. Cardiotonic agents. A topographical model for the cardiac cAMP phosphodiesterase receptor. Journal of Molecular Pharmacology 33: 1–13, 1988
Fabiato A, Fabiato F. Calcium and cardiac excitation-contraction coupling. Annual Reviews of Physiology 41: 473–484, 1979
Farah AE, Alousi AA. New cardiotonic agents search for digitalis substitute. Life Science 22: 1139–1148, 1978
Feldman MD, Copelas L Gwathmey JK, Philipps P, Warren SE, et al. Deficient production of cyclic AMP: pharmacologic evidence of an important cause of contractile dysfunction in patients with end-state heart failure. Circulation 75: 331–339, 1987
Ferrick KJ, Fein SA, Ferrick AM, Keane AT, Wright EM, et al. Effects of milrinone on ventricular arrhythmias in patients with congestive heart failure. Abstract no. 2027. Circulation 74 (Suppl. II): 11–508, 1986
Ferry DR, Kennedy GT, ORourke RA, Crawford MH. Hemodynamic effects of prolonged intravenous therapy with enoximone in patients with severe congestive heart failure. Journal of Cardiovascular Pharmacology 11: 115–122, 1988
Firth B, Ratner AV, Grassman ED, Winniford MD, Nicod P, Hillis LD. Assessment of the inotropic and vasodilator effects of amrinone versus isoproterenol. American Journal of Cardiology 54: 1331–1336, 1984
Fischer THA, Rohmann S, Treese N, Erbel R, Meyer J. What is the mode of action of ACE inhibitors in congestive heart failure? Letter to the Editor. New England Journal of Medicine 326: 1220, 1992
Franciosa JA. Intravenous amrinone: an advantage or a wrong step? Annuals of Internal Medicine 102: 399–400, 1985
Fujino K, Sperelakis N, Solaro RJ. Sensitization of dog and guinea pig heart myofilaments to calcium activation and the inotropic effect of pimobendan: comparison with milrinone. Circulation Research 63: 911–922, 1988
Gage J, Rutman H, Lucido D, Le Jemtel TH. Additive effects of dobutamine and amrinone on myocardial contractility and ventricular performance in patients with severe heart failure. Circulation 74: 367–373, 1986
Gain KR, Appleman MM. Distribution and reputation of the phosphodiesterase of muscle tissues. In George WJ & Ignarro LJ (Eds) Advances in cyclic nucleotide research, pp. 221–231, Raven Press, New York, 1978
Gilfrich HJ, Wizke-Gross J, Romer A. Chronic therapy of severe heart failure with enoximone. Journal of Cardiovascular Pharmacology 14 (Suppl. 1): S75–S77, 1989
Goldstein RA, Geraci SA, Gray EL, Rinkenberger RL, Dougherty AH, Naccarelli. Electrophysiologic effects of milrinone in patients with congestive heart failure. American Journal of Cardiology 57: 624–628, 1986
Hagemeijer F, Brand HJ, Mechelen R. Hemodynamic effects of pimobendan given orally in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. American Journal of Cardiology 63: 571–576, 1989a
Hagemeijer F, Roth W, Brand HJ. Correlations between the cardiovascular effects of pimobendan and plasma concentrations of the parent compound and its major metabolite, UD-CG 212 CL in patients with congestive heart failure. Journal of Cardiovascular fharmacology 14 (Suppl. 2): S57–S64, 1989b
Harrison SA, Reifsnyder DH, Gallis B, Cadd GG, Beavo JA. Isolation and characterization of bovine cardiac muscle cGMP-inhibited phosphodiesterase: a receptor for new cardiotonic drugs. Journal of Molecular Pharmacology 29: 506–514, 1986
Hasenfuss G, Holubarsch C, Heiss W, Just H. Influence of UDCG-115 on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy. American Heart Journal 118: 512–519, 1989
Hasenfuss G, Holubarsch C, Heiss W, Meinertz T, Hofmann T, Just H. Influence of enoximone on myocardial energetics in patients with idiopathic dilated cardiomyopathy: comparison with nitroprusside. Journal of Cardiovascular Pharmacology 14 (Suppl. 1): S69–S74, 1989
Herrmann HC, Ruddy TD, Dec GW, Strauss HW, Boucher CA, Fifer MA. Inotropic effects of enoximone in patients with severe heart failure: demonstration by left ventricular end-systolic pressure-volume analysis. Journal of the American College of Cardiology 9: 1117–1123, 1987a
Herrmann HC, Ruddy TD, Dec GW, Strauss HW, Boucher CA,, Fifer MA. Diastolic function in patients with severe heart failure: comparison of the effects of enoximone and nitroprusside. Circulation 75: 1214–1221, 1987b
Heuer H, Frenkling B, Muller US, Gulker H. Wirkung von Amrinone bei akuter schwerer Herzinsuffizienz. Intensivmedizin und Notfallmedizin 24: 133–137, 1987
Hohnloser SH, Zehender M, Geibel A, Meinertz T, Just H. Electrophysiologic effects of enoximone in patients with congestive heart failure. Journal of Cardiovascular Pharmacology 14 (Suppl. 1): S29–S32, 1989
Holmberg SRM, Williams AJ. Phosphodiesterase inhibitors and the cardiac sarcoplasmic reticulum calcium release channel: differential effects of milrinone and enoximone. Cardiovascular Research 25: 537–545, 1991
Holmes JR, Kubo SH, Cody RJ Kligfield P. Milrinone in congestive heart failure: observation on ambulatory arrhythmias. Abstract no. 42. Circulation 70 (Suppl. II): 11–11, 1984
Holmes JR, Kubo SH, Cody RJ, Kligfield P. Milrinone in congestive heart failure: observations on ambulatory ventricular arrhythmias. American Heart Journal 110: 800–806, 1985
Holz J. Bedeutung der Myokardhypertrophie bei Herzinsuffizienz. Abstract no 5. Zeitschrift für Kardiologie 81 (Suppl. 1): 9, 1992
Honerjäger P. Drugs affecting cardiac calcium metabolism. In Baker PF (Ed.) Handbook of experimental pharmacology, Vol, 83, pp. 383–410, Springer, Heidelberg, New York, 1988
Honerjäger P, Schafer-Korting M, Reiter M. Involvement of cyclic AMP in the direct inotropic action of amrinone: biochemical and functional evidence. Naunyn-Schmiedeberg’s Archives of Pharmacology 318: 112–120, 1981
Jain P, Brown Jr EJ, Langenback EG et al. Effects of milrinone on left ventricular remodelling after acute myocardial infarction. Circulation 84: 796–804, 1991
Janicki JS, Shroff SG, Weber KT. Physiologic response to the inotropic and vasodilator properties of enoximone. American Journal of Cardiology 60: 15C-20C, 1987
Jaski BE, Fifer MA, Wright RF, Braunwald E, Colucci WS. Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure: dose-response relationship and comparison to nitroprusside. Journal of Clinical Investigation 75: 643–649, 1985
Karija T, Wille LJ, Dage RC. Studies on the mechanism of the cardiotonic activity of MDL 19,205: effects on several biochemical systems. Journal Cardiovascular Pharmacology 6: 50–55, 1984
Katz AM. Contractile proteins of the heart. Physiology reviews 50: 63–158, 1970
Katz AM. Cyclic adenosine monophosphate effects on the myocardium: a man who blows hot and cold with one breath. Journal of the American College of Cardiology 2: 143–149, 1983
Katz AM. Cardiomyopathy of overload: a major determinant of prognosis in congestive heart failure. New England Journal of Medicine 322: 100–110, 1990
Katz SD, Kubo SH, Jesupp M, Brozena S, Troha JM, Wahl J, Cohn JN, LeJemtel TH. Pimobendan improves exercise capacity in digitalized patients with severe congestive heart failure. Circulation 80 (Suppl. 11 J): 11–176, 1989
Kauffmann RF, Crowe, Utterback BG, Robertson DW. LY 195115: a potent, selective inhibitor of cyclic nucleotide phosphodiesterase located in the sarcoplasma reculum. Journal of Molecular Pharmacology 30: 609–616, 1986
Kereiakes D, Chatterjee K, Parmlay WW. Intravenous and oral MDL 17, 043 (a inotrope-vasodilator agent) in congestive heart failure: hemodynamic and clinical evaluation in 38 patients. Journal of the American College of Cardiology 4: 884–889, 1984
Kereiakes D, Chatterjee K, Parmley WW. Intravenous and oral MDL 17043 (a new inotrope-vasodilator agent) in congestive heart failure: hemodynamic and clinical investigating in 38 patients. Journal of the American College of Cardiology 4: 884–889, 1984
Kinney EL, Carlin B, Ballard JO, Burks JM, Hallahan WF, Zelis R. Clinical experience with amrinone in patients with advanced congestive heart failure. Journal of Clinical Pharmacology 22: 433–440, 1982
Kithas P, Artmann M, Thompson WJ, Strada SJ. Subcellular distribution of high-affinity type IV cyclic AMP phosphodiesterase activity in rabbit myocardium: relation to the effects of cardiotonic drugs. Circulation Research 62: 782–789, 1989
Kitzen JM, Lynch JJ, Driscoll EM, Lucche BR. Cardiac electrophysiologic and hemodynamic activity of pimobendan (UDCG 115 BSJ), a new inotropic agent. Pharmacologie Experimental Theory and Practise 244: 929–939, 1988
Klauss V, Zwehl W, Mudra H, Huber R, Schmidt R, et al. Shortterm effects of oral enoximone on hemodynamics, exercise capacity, anaerobic threshold, and arrhythmias in congestive heart failure. Klinische Wochenschrift 69: 430–435, 1991
Klein NA, Siskind SJ, Frishman WH, Sonnenblick EH, LeJemtel TH. Hemodynamic comparison of intravenous amrinone and dobutamine in patients with chronic congestive heart failure. American Journal of Cardiology 48: 170–175, 1981
Klepzig M, Kleinhans E, Bull U, Strauer BE. Amrinone in Akutund Langzeittherapie. Zeitschrift fur Kardiologie 74: 85–90, 1985
Konstam MA, Cohen SR, Weiland DS, Martin TT, Das D, et al. Relative contribution of inotropic and vasodilator effects to amrinone-induced hemodynamic improvement in congestive heart failure. American Journal of Cardiology 57: 242–248, 1986
Kubo SH, Cody RJ, Chatterjee K, Simonton C, Rutman H, et al. Acute dose range study of milrinone in congestive heart failure. American Journal of Cardiology 55: 726–730, 1985
Kubo SH, Gollub S, Boure R, Rahko P, Cobb F, et al. for the Pimobendan Multicenter Research Group. Beneficial effects of pimobendan on exercise tolerance and quality of life in patients with heart failure: results of a multicenter trial. Circulation 85: 942–949, 1992
Kukovetz WR, Poch G, Holzmann S. Cyclic nucleotides and relaxation of vascular smooth muscle. In Vanhoutte PM & Leusen I (Eds) Vasodilation, pp. 339–353, Raven Press, New York, 1981
Kullberg MP, Freeman GB, Biddlecome C, Alousi AA, Edelson J. Amrinone metabolism. Clinical Pharmacology and Therapy 29: 394–401, 1981
Lee JA, Ruegg JC, Allen DG. Effects of pimobendan, a novel inotropic agent, on intracellular calcium and tension in isolated ferret ventricular muscle. Clinical Science 76: 609–618, 1989
Leier CV, Binkley PF, Starling RC, Huss-Randolph P. Disparity between improvement in left ventricular function and changes in clinical status and exercise capacity during chronic enoximone therapy. American Heart Journal 117: 1092–1097, 1989
Leier CV, Dalpiaz K, Huss P, Hermiller JB, Magorien RD, Bashore TM, Unverferth DV. Amrinone therapy for congestive heart failure in outpatients with idiopathic dilated cardiomyopathy. American Journal of Cardiology 52: 304–309, 1983
Le Jemtel TH, Gembardo D, Chadwick B, Gutman HI, Sonnenblick EH. Milrinone for long-term therapy of severe heart failure: clinical experience with special reference to maximal exercise tolerance. Circulation 73 (Suppl. III): III–213–218, 1986
Le Jemtel TH, Keren G, Reis D, Sonnenblick EH. The role of novel inotropic agents in the treatment of heart failure. Journal of Cardiovascular Pharmacology Suppl. 9: S47–S54, 1986
Likhoff MJ, Weber KT, Andrews V. Amrinone in the treatment of chronic heart failure. Journal of the American College of Cardiology 3: 1282–1290, 1984
Ludmer PL, Bairn DS, Antman EM, Gauthier DF, Rocco MB, et al. Effects of milrinone on complex ventricular arrhythmias in congestive hart failure secondary to ischemic or idiopathic dilated cardiomyopathy. American Journal of Cardiology 59: 1351–1355, 1987
Ludmer PL, Bairn DS, Gauthier DF, Lanoue AS, Antman EM, et al. Effects of milrinone on complex ventricular arrhythmias in congestive heart failure. Abstract no. 1619. Circulation 72 (Suppl. Ill): III: 405, 1985
Mager G, Klocke RK, Volkmann A, Kux A, Hopp HW, Hilger HH. Hamodynamik unter Dobutamin und Milrinon bei Patienten mit schwerer Herzinsuffizienz im individuellen Vergleich. Zeitschrift für Kardiologie 80: 149–157, 1991
Martin JL, Likhoff MJ, Janicki LS, Lakey WK, Hirshfeld JW jr, Weber KT. Myocardial energetics and clinical response to the cardiotonic agent MDL 17,043 in advanced heart failure. Journal of the American College of Cardiology 4: 875–883, 1984
Maskin CS, Chadwick B, Sonnenblick EH, LeJemtel TH. Withdrawal and reinstitution of long-term amrinone therapy: evidence of drug dependent improvement in cardiac performance without tachyphylaxis. In Braunwald E et al. (Eds) Milrinone: investigation of new inotropic therapy for congestive heart failure, pp. 155–166, Raven Press, New York, 1984
Maskin CS, Forman R, Klein NA, Sonnenblick EH, LeJemtel TH. Long term amrinone therapy in patients with severe heart failure. American Journal of Cardiology 72: 113–119, 1982
Maskin CS, Forman R, Sonnenblick, Frishman WH, LeJemtel TH. Failure of dobutamine to increase exercise capacity despite hemodynamic improvement in severe chronic heart failure. American Journal of Cardiology 51: 177–182, 1983a
Maskin CS, Kugier J, Sonnenblick EH, LeJemtel TH. Acute inotropic stimulation with dopamine in severe congestive heart failure: beneficial hemodynamic effect at rest but not during maximal exercise. American Journal of Cardiology 52: 1028–1032, 1983b
Massie B, Bourassa M, di Bianco R, Hess M, Konstam M, et al. Long-term administration of amrinone for congestive heart failure: lack of efficacy in a multicenter controlled trial. Circulation 71: 963–971, 1985
Massie BM, Cornyn J, Topic N, Loge D, Podolin RA. Combined hemodynamic and scintigraphic assessment of piroximone (MDL 19,205) and comparison with dobutamine and nitroprusside. American Journal of Cardiology 60: 647–653, 1987
Miles WM, Heger JJ, Minardo JD, Klein LS, Prystowsky EN, Zipes DP. The electrophysiologic effects of enoximone in patients with preexisting ventricular tachyarrhythmias. American Heart Journal 117: 112–121, 1989
Mitrovic V, Thormann J, Neutzner J, Bahawar H, Volz M, et al. Hemodynamic, antiischemic, and neurohumoral effects of enoximone in patients with coronary artery disease. American Heart Journal 117: 106–111, 1989
Monrad ES, Bairn DS, Smith HS, Lanoue A, Braunwald E, Grossman W. Effects of milrinone on coronary hemodynamics and myocardial energetics in patients with congestive heart failure. Circulation 5: 972–979, 1985a
Monrad ES, Bairn DS, Smith HS, Lanoue A. Braunwald E, Grossman W. Effects of milrinone on coronary hemodynamics and myocardial energetics in patients with congestive heart failure. Circulation 71: 972–979, 1985b
Monrad ES, McKay RG, Bairn DS. Improvement in indices of diastolic performance in patients with congestive heart failure treated with milrinone. Circulation 70: 1030–1037, 1984
Morad M, Cleeman C. Role of calcium channel in development of tension in heart muscle. Journal of Molecular and Cellular Cardiology 19: 527–553, 1978
Morgan JP, Gwathmey JK, deFeo TT, Morgan KG. The effects of amrinone and related drugs on intracellular calcium in isolated mamillian cardiac and vascular smooth muscle. Circulation 73 (Suppl. III): 111–65–76, 1986
Morgan JP, Perreault CL, Morgan KG. The cellular basis of contraction and relaxation in cardiac and vascular smooth muscle. American Heart Journal 121: 961–968, 1991a
Morgan JP. Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. New England Journal of Medicine 325: 625–632, 1991b
Nemanich JW, Shurman AJ, Rossen JD, Kremser C, Davis F, Rajfer SI. Effects of long-term therapy with oral piroximone on resting hemodynamics, peak aerobic capacity and the anaerobic threshold in patients with heart failure. Journal of Cardiovascular Pharmacology 10: 580–588, 1987
Packer M, Medina N, Yushak M. Hemodynamic and clinical limitations of long-term inotropic therapy with amrinone in patients with severe chronic heart failure. Circulation 70: 1038–1047, 1984a
Packer M, Medina N, Yushak M. Failure of low doses of amrinone to produce sustained hemodynamic improvement in patients with severe chronic congestive heart failure. American Journal of Cardiology 54: 1025–1029, 1984b
Packer M, Medina N, Yushak M. Comparative immediate hemodynamic and hormonal effects of amrinone and captopril in patients with severe chronic heart failure. American Journal of Medical Sciences 291: 815, 1986
Packer M. Vasodilator and inotropic drugs for the treatment of chronic heart failure: distinguishing type from hope. Journal of the American College of Cardiology 12: 1299–1317, 1988
Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, diBianco R, et al. for the PROMISE Study Research Group. Effect of oral milrinone on mortality in severe chronic heart failure. New England Journal of Medicine 325: 1468–1475, 1991
Pang DC. Cyclic AMP and cyclic GMP phosphodiesterase: target for drug development. Drugs Development Research 12: 85–92, 1988
Petein M, Levine TB, Cohn JN. Hemodynamic effects of a new inotropic agent, piroximone (MDL 19,205) in patients with chronic heart failure. Journal of the American College of Cardiology 4: 364–371, 1984
Petein M, Levine TB, Cohn JM. Persistent hemodynamic effects without long-term clinical benefits in response to oral piroximone (MDL 19205) in patients with congestive heart failure. Circulation 73 (Suppl. III). III–230–236, 1986
Petein M, Pierpont GL, Heppner B, Bache RJ, Cohn JM. Hemodynamic and regional blood flow response to MDL 19,205 in dogs: a comparison with dobutamine. Circulation 68 (Suppl. III): 128, 1983
Podolin R, Massie B, Topic N, Szlachcic J, Loge D. Comparison of intravenous MDL 19,205 and dobutamine in severe heart failure. Journal of the American College of Cardiology 5: 509, 1985
Pop T, Treese N, Cremer GMJ, Haegele KD, Meyer J. Electrophysiological effects of intravenous MDL 17, 043. International Journal of Cardiology 12: 223–232, 1986
Rettig G, Sen S, Frohlich G, Schieffer H, Bette L. Withdrawal of long-term amrinone therapy in patients with congestive heart failure: a placebo controlled trial. European Heart Journal 7: 628–631, 1986
Ribeiro JP, White HD, Arnold JMO, Hartley LH, Colucci WS. Exercise response before and after long term treatment with oral milrinone in patients with severe heart failure. American Journal of Medicine 81: 759–764, 1986
Robertson SP, Johnson JD, Holroyde MJ, Kranias EG, Potter JD, Solaro RJ. The effect of troponin I phosphorylation on the calcium binding properties of the calcium regulatory site of bovine cardiac troponin. Journal of Biological Chemistry 257: 260–263, 1982
Rubin SA, Tabak L. MDL 17,043: short and long-term cardiopulmonary and clinical effects in patients with heart failure. Journal of the American College of Cardiology 5: 1422–1427, 1985
Ruegg JC. Effects of new inotropic agents on calcium sensitivity of contractile proteins. Circulation 73 (Suppl. III): 111–78–84, 1986
Schlepper M, Mitrovic V, Thormann J. Wirkungen der Phosphodiesterase-III-Hemmer bei ischämischer Herzerkrankung. Zeitschrift für Kardiologie 80 (Suppl. 4): 75–83, 1991
Schmitz W, v der Leyen H, Meyer W, Neumann J, Scholz H. Phosphodiesterase inhibition and and positive inotropic effects. Journal of Cardiovascular Pharmacology 14 (Suppl. 3): 511–514, 1989
Scholz H, Meyer W. Phosphodiesterase-inhibiting properties of newer inotropic agents. Circulation 73 (Suppl. III): III–99–108, 1986
Scriven AJL, Lipkin DP, Anand IS, Sutton GC, Poole-Wilson PA. A comparison of hemodynamic effects of one-month oral captopril and enoximone treatment for severe congestive heart failure. American Journal of Cardiology 60: 68C-71C, 1987
Scriven AJL, Lipkin DP, Anand IS, Sutton GC, Poole-Wilson PA. Double-blind, randomized, cross-over comparison of oral captopril and enoximone added to diuretic treatment in patients with severe heart failure. Journal of Cardiovascular Pharmacology 11: 45–50, 1988
Shah PK, Amin DK, Hulse S, Shellock F, Swan HJC. Inotropic therapy for refractory congestive heart failure with oral fenoximone (MDL-17,043): poor long term results despite early hemodynamic and clinical improvement. Circulation 71: 326–332, 1985
Siegel LA, Keung E, Siskind SJ, Forman R, Feinberg H, et al. Beneficial effects of amrinone-hydralazine combination on resting hemodynamics and exercise capacity in patients with severe congestive heart failure. Circulation 63: 839–844, 1981
Siegel LA, LeJemtel TH, Strom J, Maskin C, Forman R, et al. Improvement in exercise capacity despite cardiac deterioration: noninvasive assessment of long-term therapy with amrinone in severe heart failure. American Heart Journal 106: 1042–1047, 1983
Siegl PKS, Morgan G, Sweet CS. Response to amrinone in isolated cardiac muscles from cat, rabbit, and guinea-pig Journal of Cardiovascular Pharmacology 6: 281–287, 1984
Silke B, Verma SP, Midtbo KA, Reynolds G, Taylor SH. Comparative haemodynamic dose-response effects of dobutamine and amrinone in left ventricular failure complicating acute myocardial infarction. Journal of Cardiovascular Pharmacology 9: 19–25, 1987
Silverman BD, Merrill AJ, Gerber L. Clinical effects and side effects of amrinone. Archives of Internal Medicine 145: 825–829, 1985
Simonton CA, Chatterjee K, Cody RJ. Milrinone in congestive heart failure: acute and chronic hemodynamic and clinical evaluation. Journal of the American College of Cardiology 6: 453–459, 1985
Sinoway LS, Maskin CS, Chadwik B, Forman R, Sonnenblick EH, LeJemtel T. Long-term therapy with a new cardiotonic agent, WIN 47203: drug dependent improvement in cardiac performance and procession of the underlying disease. Journal of the American College of Cardiology 2: 327–331, 1983
Siskind SJ, Sonnenblick EH, Forman R, Scheuer J, LeJemtel TH. Acute substantial benefit of inotropic therapy with amrinone on exercise hemodynamics and metabolism in severe congestive heart failure. Circulation 64: 966–973, 1981
Solaro RJ, Ruegg JC. Stimulation of calcium binding and ATPase activity of dog cardiac myofibrils by AR-L 115BS, a novel cardiotonic agent. Circulation Research 51: 290–294, 1982
Stroshane RM, Benziger DP, Edelson J. Pharmacokinetics of milrinone in congestive heart failure patients. In Braunwald E et al. (Eds) Milrinone: investigation of new inotropic therapy for congestive heart failure, pp. 119–132, Raven Press, New York, 1984
Tenor H, Bartel S, Krause EG. Cyclic nucleotide phosphodiesterase activity in the rat myocardium: evidence of four different PDE subtypes. Biomedical and Biochemistry Acta 46: 749–753, 1987
The Xamoterol in Severe Heart Failure Study Group. Xamoterol in severe heart failure. Lancet 336: 1–6, 1990
Thormann J, Kramer W, Kindler M, Kremer P, Schlepper M. BestimmVung der Wirkkomponenten von Amrinon durch kontinuierliche Analyse der Druck-Volumen-Beziehungen; Anwendung der Conductance-(Volumen)-Kathetertechnik und der schnellen Lastande rung durch Ballonokklusion der V.cava inferior. Zeitschrift fur Kardiologie 76: 530–540, 1987
Thormann J, Hueting J, Kremer P, Wissemann J, Mitrovic V, Dieterich HA, Schlepper M. Enoximone: true inotropic effects Do they cause ischemia. Analysis of end-systolic pressure-volume relations using the conductance (volume) catheter technique. Cardiovascular Drugs and Therapy 4: 1403–1416, 1990
Timmis AD, Smyth P, Jewitt DE. Milrinone in heart failure. Effects on exercise haemodynamics during short term treatment. British Heart Journal 54: 42–47, 1985
Trautwein W, Hescheler J. Regulation of cardiac L-type calcium current by phosphorylation and G-proteins. Annual Reviews of Physiology 52: 257–274, 1990
Treese N, Erbel R, Rhein S, Diefenbach C, Alken RG, Mohr-Kahaly S, Meyer J. Langzeittherapie der chronischen Herzinsuffizienz mit Enoximon. Deutsche Medizinische Wochenschrift 112: 1163–1169, 1987a
Treese N, Erbel R, Pilcher J, Choraria S, Rhein S, et al. Longterm treatment with oral enoximone for chronic congestive heart failure: the European experience. American Journal of Cardiology 60: 85C-9OC, 1987b
Treese N, Erbel R, Rhein S, Henrichs KJ, Meyer J. Additive effects of enoximone and nitroprusside in unstable chronic heart failure. European Heart Journal 10: 484–492, 1989a
Treese N, Rhein S, Erbel R, Meyer J. Long-term enoximone therapy in unstable chronic heart failure. Journal of Cardiovascular Pharmacology 14 (Suppl. 1): S78–S83, 1989b
Treese N, Rhein S, Werneyer A, Erbel R, von Olshausen K, Meyer J. Der Einfluss oraler Enoximon-Langzeittherapie auf das Arrhythmieprofil bei chronischer Herzinsuffizienz. Zeitschrift für Kardiologie 77: 653–659, 1988
Uretsky BF, Generalovich T, Reddy PS, Spangenberg RB, Follansbee WP. The acute hemodynamic effects of a new agent, MDL 17,043, in the treatment of congestive heart failure. Circulation 67: 823–828, 1983
Uretsky BF, Generalovich T, Verbalis JG, Valdes AM, Reddy PS. MDL 17,043 therapy in severe congestive heart failure: characterization of the early and late hemodynamic, pharmacokinetic, hormonal and clinical response. Journal of the American College of Cardiology 5: 1414–1421, 1985
Uretsky BF, Valdes AM. Reddy PS. Positive inotropic therapy for short-term management of patients with congestive heart failure: hemodynamic effects and clinical efficacy of MDL 17,043. Circulation 73 (Suppl. III): III–219–229, 1986
Uretsky BF, Jesupp M, Konstam MA, Dec W, Leier CV, et al. for the Enoxiomone Multicenter Trial Group. Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure: lack of benefit compared with placebo. Circulation 82: 774–780, 1990
van der Leyen H, Brunkhorst D, Meyer W, Scholz H. Positive inotropic and chronotropic effects and phosphodiesterase III inhibition of new cardiotonic agents. Circulation 76 (Suppl. IV): IV–155, 1987
van der Leyen H, Meyer W, Scholz H. Positive inotropic and chronotropic effects of phosphodiesterase III inhibition of new cardiotonic agents. Abstract no. 155. Circulation 76 (Suppl. IV): IV–155, 1987
Vernon MW, Heel RC, Brogden RN. Enoximone. A review of its pharmacological properties and therapeutic potential. Drugs 42: 997–1017, 1991
Viquerat CE, Kereiakes D, Morris DL. Alterations in left ventricular function, coronary hemodynamics and myocardial catecholamine balance with MDL 17,043, a new inotropic vasodilator agent, in patients with severe heart failure. Journal of the American College of Cardiology 5: 326–332, 1985
Weber KT, Andrews V, Janicki JS, Wilson JR, Fishman AP. Amrinone and exercise performance in patients with chronic heart failure. American Journal of Cardiology 48: 164–169, 1981
Weber KT, Janicki JS, Jain MC Piroximone (MDL 19205) in the treatment of unstable and stable chronic cardiac failure. American Heart Journal 114: 805–813, 1987
Weishaar RE, Cain MH, Bristol JA. A new generation of phosphodiesterase inhibitors: multiple forms of phosphodieaterase and the potential for drug selectivity. Journal of Medical Chemistry 28: 537–545, 1985
Weishaar RE, et al. Multiple molecular forms of cyclic nucleotide phosphodiesterase in cardiac and smooth muscle and in platelets. Isolation, characterization, and effects of various reference phosphodiesterase inhibitors and cardiotonic agents. Biochemical Pharmacology 35: 787–800, 1986
Weishaar RE, Kobylarz-Singer DC, Steffen RD, Kaplan HR. Subclasses of cyclic AMP specific phosphodiesterase in left ventricular muscle and their improvement in regulating myocardial contractility. Circulation Research 61: 539–547, 1987
White HD, Ribeiro JP, Hartley LH, Colucci WS. Immediate effects of milrinone on metabolic and sympathetic responses to exercise in severe heart failure. American Journal of Cardiology 56: 93–98, 1985
Wilmshurst PT, Thompson DS, Jenkins BS, Coltart DJ, Webb-Peploe MM. Haemodynamic effects of intravenous amrinone in patients with impaired left ventricular function. British Heart Journal 49: 77–82, 1983a
Wilmshurst PT, Webb-People MM. Side effects of amrinone therapy. British Heart Journal 49: 447–451, 1983b
Wilmshurst PT, Thompson DS, Juul SM, Jenkins BS, Coltart DJ, Webb-Peploe MM. Comparison of the effects of amrinone and sodium nitroprusside on haemodynamics, contractility and myocardial metabolism in patients with cardiac failure due to coronary artery disease and dilated cardiomyopathy. British Heart Journal 52: 38–48, 1984
Wynne J, Malacoff RF, Benoti JR, Curfman GD, Grossman W, et al. Oral amrinone in refractory congestive heart failure. American Journal of Cardiology 45: 1245–1249, 1980
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fischer, T.A., Erbel, R. & Treese, N. Current Status of Phosphodiesterase Inhibitors in the Treatment of Congestive Heart Failure. Drugs 44, 928–945 (1992). https://doi.org/10.2165/00003495-199244060-00003
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199244060-00003