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(Circulation. 1996;94:2817-2825.)
© 1996 American Heart Association, Inc.
Articles |
Comparative Hemodynamic, Left Ventricular Functional, and Antiadrenergic Effects of Chronic Treatment With Metoprolol Versus Carvedilol in the Failing Heart
the University of Utah School of Medicine (E.M.G., S.O., P.M., P.L.), Salt Lake City, and the University of Colorado Health Sciences Center (W.T.A., B.H., M.W., M.R.B.), Denver.
Correspondence to Michael Bristow, Division of Cardiology, Campus Box B-139, University of Colorado Health Sciences Center, 4200 E 9th Ave, Denver, CO 80262. E-mail Michael.Bristow@UCHSC.edu.
Background The basic pharmacology of the third-generation ß-blocking agent carvedilol differs considerably from second-generation compounds such as metoprolol. Moreover, carvedilol may produce different, ie, more favorable, clinical effects in chronic heart failure. For these reasons, we compared the effects of carvedilol and metoprolol on adrenergic activity, receptor expression, degree of clinical ß-blockade, hemodynamics, and left ventricular function in patients with mild or moderate chronic heart failure.
Methods and Results The effects of carvedilol versus metoprolol were compared in two concurrent placebo-controlled trials with carvedilol or metoprolol that had common substudies focused on adrenergic, hemodynamic, and left ventricular functional measurements. All subjects in the substudies had chronic heart failure resulting from idiopathic dilated cardiomyopathy. Carvedilol at 50 to 100 mg/d produced reductions in exercise heart rate that were similar to metoprolol at 125 to 150 mg/d, indicating comparable degrees of ß-blockade. Compared with metoprolol, carvedilol was associated with greater improvement in New York Heart Association functional class. Although there were no significant differences in hemodynamic effects between the carvedilol and metoprolol active-treatment groups, carvedilol tended to produce relatively greater improvements in left ventricular ejection fraction, stroke volume, and stroke work compared with changes in the respective placebo groups. Carvedilol selectively lowered coronary sinus norepinephrine levels, an index of cardiac adrenergic activity, whereas metoprolol did not lower coronary sinus norepinephrine and actually increased central venous norepinephrine levels. Finally, metoprolol was associated with an increase in cardiac ß-receptor density, whereas carvedilol did not change cardiac ß-receptor expression.
Conclusions The third-generation ß-blocking agent carvedilol has substantially different effects on left ventricular function, hemodynamics, adrenergic activity, and ß-receptor expression than does the second-generation compound metoprolol. Some or all of these differences may explain the apparent differences in clinical results between the two compounds.
Key Words: heart failure • receptors, adrenergic, beta • nervous system, autonomic
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|
|
|
|
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|
|
|
 |
|
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|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 M. L. Kukin {beta}-Blockers in Chronic Heart Failure: Considerations for Selecting an Agent Mayo Clin. Proc., November 1, 2002; 77(11): 1199 - 1206. [Abstract] [PDF]
|
|
|
|
|
|
M. Metra, S. Nodari, A. D'Aloia, C. Muneretto, A. D. Robertson, M. R. Bristow, and L. Dei Cas Beta-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: A randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol J. Am. Coll. Cardiol., October 2, 2002; 40(7): 1248 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W.H. Fung, S. K.W. Chan, L. Y.C. Yeung, and J. E. Sanderson Is beta-blockade useful in heart failure patients with atrial fibrillation? An analysis of data from two previously completed prospective trials Eur J Heart Fail, August 1, 2002; 4(4): 489 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Thackray, J. Easthaugh, N. Freemantle, and J. G.F. Cleland The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure--a meta-regression analysis Eur J Heart Fail, August 1, 2002; 4(4): 515 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Jourdain, F. Funck, Y. Fulla, A. Hagege, M. Bellorini, N. Guillard, J. Loiret, B. Thebault, and M. Desnos Myocardial contractile reserve under low doses of dobutamine and improvement of left ventricular ejection fraction with treatment by carvedilol Eur J Heart Fail, June 1, 2002; 4(3): 269 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zugck, A. Haunstetter, C. Kruger, R. Kell, D. Schellberg, W. Kubler, and M. Haass Impact of beta-blocker treatment on the prognostic value of currently used risk predictors in congestive heart failure J. Am. Coll. Cardiol., May 15, 2002; 39(10): 1615 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Lowes, E. M. Gilbert, W. T. Abraham, W. A. Minobe, P. Larrabee, D. Ferguson, E. E. Wolfel, J. Lindenfeld, T. Tsvetkova, A. D. Robertson, et al. Myocardial Gene Expression in Dilated Cardiomyopathy Treated with Beta-Blocking Agents N. Engl. J. Med., May 2, 2002; 346(18): 1357 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Goldstein Benefits of {beta}-Blocker Therapy for Heart Failure: Weighing the Evidence Arch Intern Med, March 25, 2002; 162(6): 641 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Doi, M. Yano, S. Kobayashi, M. Kohno, T. Tokuhisa, S. Okuda, M. Suetsugu, Y. Hisamatsu, T. Ohkusa, M. Kohno, et al. Propranolol Prevents the Development of Heart Failure by Restoring FKBP12.6-Mediated Stabilization of Ryanodine Receptor Circulation, March 19, 2002; 105(11): 1374 - 1379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Richardt, D. Richardt, S. Adler, E. Kraatz, A. Notzold, and T. Kurz Unique effects of carvedilol on noradrenaline release in the human heart Eur J Heart Fail, March 1, 2002; 4(2): 147 - 149. [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Foody, M. H. Farrell, and H. M. Krumholz {beta}-Blocker Therapy in Heart Failure: Scientific Review JAMA, February 20, 2002; 287(7): 883 - 889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Buchhorn, M. Hulpke-Wette, W. Ruschewski, R. Pregla, J. Fielitz, R. Hetzer, and V. Regitz-Zagrosek {beta}-Receptor downregulation in congenital heart disease: a risk factor for complications after surgical repair? Ann. Thorac. Surg., February 1, 2002; 73(2): 610 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A Nikolaidis, T. Hentosz, A. Doverspike, R. Huerbin, C. Stolarski, Y.-T. Shen, and R. P Shannon Catecholamine stimulation is associated with impaired myocardial O2 utilization in heart failure Cardiovasc Res, February 1, 2002; 53(2): 392 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zaugg, M. C. Schaub, T. Pasch, and D. R. Spahn Modulation of {beta}-adrenergic receptor subtype activities in perioperative medicine: mechanisms and sites of action Br. J. Anaesth., January 1, 2002; 88(1): 101 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Reiken, M. Gaburjakova, J. Gaburjakova, K.-l. He, A. Prieto, E. Becker, G.-h. Yi, J. Wang, D. Burkhoff, and A. R. Marks {beta}-Adrenergic Receptor Blockers Restore Cardiac Calcium Release Channel (Ryanodine Receptor) Structure and Function in Heart Failure Circulation, December 4, 2001; 104(23): 2843 - 2848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mak and G. E. Newton The Oxidative Stress Hypothesis of Congestive Heart Failure : Radical Thoughts Chest, December 1, 2001; 120(6): 2035 - 2046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kubo, E. R. Azevedo, G. E. Newton, J. D. Parker, and J. S. Floras Lack of evidence for peripheral alpha1- adrenoceptor blockade during long-term treatment of heart failure with carvedilol J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1463 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Azevedo, T. Kubo, S. Mak, A. Al-Hesayen, A. Schofield, R. Allan, S. Kelly, G. E. Newton, J. S. Floras, and J. D. Parker Nonselective Versus Selective {beta}-Adrenergic Receptor Blockade in Congestive Heart Failure: Differential Effects on Sympathetic Activity Circulation, October 30, 2001; 104(18): 2194 - 2199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Maack, T. Elter, G. Nickenig, K. LaRosee, M. Crivaro, A. Stablein, H. Wuttke, and M. Bohm Prospective crossover comparison of carvedilol and metoprolol in patients with chronic heart failure J. Am. Coll. Cardiol., October 1, 2001; 38(4): 939 - 946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kubo, K. B. Margulies, V. Piacentino III, J. P. Gaughan, and S. R. Houser Patients With End-Stage Congestive Heart Failure Treated With {beta}-Adrenergic Receptor Antagonists Have Improved Ventricular Myocyte Calcium Regulatory Protein Abundance Circulation, August 28, 2001; 104(9): 1012 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Erdmann, J.o. Raible, J. Maki-Abadi, M. Hummel, J. Hammann, B. Wollnik, E. Frantz, E. Fleck, R. Hetzer, and V. Regitz-Zagrosek Spectrum of clinical phenotypes and gene variants in cardiac myosin-binding protein C mutation carriers with hypertrophic cardiomyopathy J. Am. Coll. Cardiol., August 1, 2001; 38(2): 322 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Stanek, B. Frey, M. Hulsmann, R. Berger, B. Sturm, J. Strametz-Juranek, J. Bergler-Klein, P. Moser, A. Bojic, E. Hartter, et al. Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction J. Am. Coll. Cardiol., August 1, 2001; 38(2): 436 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.K. Agarwal and P. Venugopalan Beneficial effect of carvedilol on heart rate response to exercise in digitalised patients with heart failure in atrial fibrillation due to idiopathic dilated cardiomyopathy Eur J Heart Fail, August 1, 2001; 3(4): 437 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gullestad, C. Manhenke, T. Aarsland, R. Skardal, H. Fagertun, J. Wikstrand, and J. Kjekshus Effect of metoprolol CR/XL on exercise tolerance in chronic heart failure -- a substudy to the MERIT-HF trial Eur J Heart Fail, August 1, 2001; 3(4): 463 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. De Boer, D. J. Van Veldhuisen, M. Metra, R. Giubbini, S. Nodari, E. Boldi, M. Grazia Modena, and L. Dei Cas {beta}-Blockade in Chronic Heart Failure Response Circulation, June 12, 2001; 103 (23): e118 - e118. [Full Text] [PDF]
|
|
|
|
|
|
K. Stoschitzky, G. Koshucharova, R. Zweiker, R. Maier, N. Watzinger, F. M. Fruhwald, and W. Klein Differing beta-blocking effects of carvedilol and metoprolol Eur J Heart Fail, June 1, 2001; 3(3): 343 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
The Beta-Blocker Evaluation of Survival Trial Inve A Trial of the Beta-Blocker Bucindolol in Patients with Advanced Chronic Heart Failure N. Engl. J. Med., May 31, 2001; 344(22): 1659 - 1667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Kaye, L. Johnston, G. Vaddadi, H. Brunner-LaRocca, G. L. Jennings, and M. D. Esler Mechanisms of Carvedilol Action in Human Congestive Heart Failure Hypertension, May 1, 2001; 37(5): 1216 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Camici and D. P. Dutka Repetitive stunning, hibernation, and heart failure: contribution of PET to establishing a link Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H929 - H936. [Full Text] [PDF]
|
|
|
|
|
|
M. Flesch, S. Ettelbruck, S. Rosenkranz, C. Maack, B. Cremers, K.-D. Schluter, O. Zolk, and M. Bohm Differential effects of carvedilol and metoprolol on isoprenaline-induced changes in {beta}-adrenoceptor density and systolic function in rat cardiac myocytes Cardiovasc Res, February 1, 2001; 49(2): 371 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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X.-J. Du, X.-M. Gao, G. L. Jennings, A. M. Dart, and E. A. Woodcock Preserved ventricular contractility in infarcted mouse heart overexpressing beta 2-adrenergic receptors Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2456 - H2463. [Abstract] [Full Text] [PDF]
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M. R. Bristow What Type of {beta}-Blocker Should Be Used to Treat Chronic Heart Failure? Circulation, August 1, 2000; 102(5): 484 - 486. [Full Text] [PDF]
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M. Metra, R. Giubbini, S. Nodari, E. Boldi, M. G. Modena, and L. D. Cas Differential Effects of {beta}-Blockers in Patients With Heart Failure : A Prospective, Randomized, Double-Blind Comparison of the Long-Term Effects of Metoprolol Versus Carvedilol Circulation, August 1, 2000; 102(5): 546 - 551. [Abstract] [Full Text] [PDF]
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W. T. Abraham {beta}-Blockers: The New Standard of Therapy for Mild Heart Failure Arch Intern Med, May 8, 2000; 160(9): 1237 - 1247. [Abstract] [Full Text] [PDF]
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S. F. Vatner, D. E. Vatner, and C. J. Homcy {beta}-Adrenergic Receptor Signaling: An Acute Compensatory Adjustment--Inappropriate for the Chronic Stress of Heart Failure? : Insights from Gs{alpha} Overexpression and Other Genetically Engineered Animal Models Circ. Res., March 17, 2000; 86(5): 502 - 506. [Full Text] [PDF]
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M. Ungerer, H.-J. Weig, S. Kubert, M. Overbeck, F. Bengel, A. Schomig, and M. Schwaiger Regional pre- and postsynaptic sympathetic system in the failing human heart -- regulation of {beta}ARK-1 Eur J Heart Fail, March 1, 2000; 2(1): 23 - 31. [Abstract] [Full Text] [PDF]
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M. R. Bristow {beta}-Adrenergic Receptor Blockade in Chronic Heart Failure Circulation, February 8, 2000; 101(5): 558 - 569. [Full Text] [PDF]
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Effects of Metoprolol CR in Patients With Ischemic and Dilated Cardiomyopathy : The Randomized Evaluation of Strategies for Left Ventricular Dysfunction Pilot Study Circulation, February 1, 2000; 101(4): 378 - 384. [Abstract] [Full Text] [PDF]
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F. Romeo, D. Li, M. Shi, and J. L Mehta Carvedilol prevents epinephrine-induced apoptosis in human coronary artery endothelial cells: modulation of Fas/Fas ligand and caspase-3 pathway Cardiovasc Res, February 1, 2000; 45(3): 788 - 794. [Abstract] [Full Text] [PDF]
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 O.-E. Brodde and M. C. Michel Adrenergic and Muscarinic Receptors in the Human Heart Pharmacol. Rev., December 1, 1999; 51(4): 651 - 690. [Abstract] [Full Text] [PDF]
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J. E. Sanderson, S. K. W. Chan, G. Yip, L. Y. C. Yeung, K. W. Chan, K. Raymond, and K. S. Woo Beta-blockade in heart failure: A comparison of carvedilol with metoprolol J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1522 - 1528. [Abstract] [Full Text] [PDF]
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 C.H. Davies and Y. Bashir Beta-blockers for heart failure-time to think the unthinkable? QJM, November 1, 1999; 92(11): 673 - 678. [Full Text] [PDF]
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M. A. Movsesian Beta-adrenergic receptor agonists and cyclic nucleotide phosphodiesterase inhibitors: shifting the focus from inotropy to cyclic adenosine monophosphate J. Am. Coll. Cardiol., August 1, 1999; 34(2): 318 - 324. [Abstract] [Full Text] [PDF]
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M. Flesch, C. Maack, B. Cremers, A. T. Baumer, M. Sudkamp, and M. Bohm Effect of {beta}-Blockers on Free Radical–Induced Cardiac Contractile Dysfunction Circulation, July 27, 1999; 100(4): 346 - 353. [Abstract] [Full Text] [PDF]
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A. Di Lenarda, G. Sabbadini, L. Salvatore, G. Sinagra, L. Mestroni, B. Pinamonti, D. Gregori, F. Ciani, A. Muzzi, S. Klugmann, et al. Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol J. Am. Coll. Cardiol., June 1, 1999; 33(7): 1926 - 1934. [Abstract] [Full Text] [PDF]
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P. A. O'Callaghan and A. J. Camm Treatment of arrhythmias in heart failure Eur J Heart Fail, June 1, 1999; 1(2): 133 - 137. [Full Text] [PDF]
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M. L. Kukin, J. Kalman, R. H. Charney, D. K. Levy, C. Buchholz-Varley, O. N. Ocampo, and C. Eng Prospective, Randomized Comparison of Effect of Long-Term Treatment With Metoprolol or Carvedilol on Symptoms, Exercise, Ejection Fraction, and Oxidative Stress in Heart Failure Circulation, May 25, 1999; 99(20): 2645 - 2651. [Abstract] [Full Text] [PDF]
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G. E. Newton, E. R. Azevedo, and J. D. Parker Inotropic and Sympathetic Responses to the Intracoronary Infusion of a ß2-Receptor Agonist : A Human In Vivo Study Circulation, May 11, 1999; 99(18): 2402 - 2407. [Abstract] [Full Text] [PDF]
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D. M. Kaye, A. M. Dart, G. L. Jennings, and M. D. Esler Antiadrenergic effect of chronic amiodarone therapy in human heart failure J. Am. Coll. Cardiol., May 1, 1999; 33(6): 1553 - 1559. [Abstract] [Full Text] [PDF]
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K.-L. Laugwitz, M. Ungerer, T. Schoneberg, H.-J. Weig, K. Kronsbein, A. Moretti, K. Hoffmann, M. Seyfarth, G. Schultz, and A. Schomig Adenoviral Gene Transfer of the Human V2 Vasopressin Receptor Improves Contractile Force of Rat Cardiomyocytes Circulation, February 23, 1999; 99(7): 925 - 933. [Abstract] [Full Text] [PDF]
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G. S. Pepper and R. W. Lee Sympathetic Activation in Heart Failure and Its Treatment With {beta}-Blockade Arch Intern Med, February 8, 1999; 159(3): 225 - 234. [Abstract] [Full Text] [PDF]
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W. Carlson and K. Oberg Clinical Pharmacology of Carvedilol Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(4): 205 - 218. [Abstract] [PDF]
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W. H. Frishman Carvedilol N. Engl. J. Med., December 10, 1998; 339(24): 1759 - 1765. [Full Text] [PDF]
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T. Anzai, N. C. Lai, M. Gao, and H. K. Hammond Dissociation between regional dysfunction and beta -adrenergic receptor signaling in heart failure Am J Physiol Heart Circ Physiol, October 1, 1998; 275(4): H1267 - H1273. [Abstract] [Full Text] [PDF]
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M. Bohm, S. Ettelbruck, M. Flesch, W. H van Gilst, A. Knorr, C. Maack, Y. M Pinto, M. Paul, A. C.H Teisman, and O. Zolk {beta}-Adrenergic signal transduction following carvedilol treatment in hypertensive cardiac hypertrophy Cardiovasc Res, October 1, 1998; 40(1): 146 - 155. [Abstract] [Full Text] [PDF]
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D. K. Rohrer, E. H. Schauble, K. H. Desai, B. K. Kobilka, and D. Bernstein Alterations in dynamic heart rate control in the beta 1-adrenergic receptor knockout mouse Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1184 - H1193. [Abstract] [Full Text] [PDF]
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 D. K. ROHRER and B. K. KOBILKA G Protein-Coupled Receptors: Functional and Mechanistic Insights Through Altered Gene Expression Physiol Rev, January 1, 1998; 78(1): 35 - 52. [Abstract] [Full Text] [PDF]
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M. L Kukin, J. Kalman, M. M Mannino, C. Buchholz-Varley, and O. Ocampo beta Blockade in congestive heart failure: persistent adverse haemodynamic effects during chronic treatment with subsequent doses Heart, November 1, 1997; 78(5): 444 - 449. [Abstract] [Full Text] [PDF]
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K. Ogunyankin and B. N. Singh Reflections on Recent Clinical Trials in Patients With Heart Failure and Those With Reduced Ventricular Function Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1997; 2(3): 147 - 152. [PDF]
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