From the Departments of Physiology (K.D., J.A.M., S.R.H.), Internal
Medicine (K.B.M.), and Surgery (V.J.), Temple University School of Medicine,
Philadelphia, Pa.
Correspondence to Kenneth B. Margulies, MD, Assistant Professor of Medicine and Physiology, Room 318, OMS Bldg, Temple University School of Medicine, 3400 N Broad St, Philadelphia, PA 19140. E-mail margul{at}astro.ocis.temple.edu
Background—The failing
myocardium is characterized by decreased force
production, slowed relaxation, and depressed responses to
ß-adrenergic stimulation. In some heart failure patients, heart
function is so poor that a left ventricular assist device
(LVAD) is inserted as a bridge to transplantation. In the present
research, we investigated whether circulatory support with an LVAD
influenced the functional properties of myocytes from the failing
heart.
Methods and Results—Myocytes were isolated from human explanted
failing hearts (HF-myocytes) and failing hearts with antecedent LVAD
support (HF-LVAD-myocytes). Studies of myocyte function indicated that
the magnitude of contraction was greater (9.6±0.7% versus 6.9±0.5%
shortening), the time to peak contraction was significantly abbreviated
(0.37±0.01 versus 0.75±0.04 seconds), and the time to 50% relaxation
was reduced (0.55±0.02 versus 1.45±0.11 seconds) in the
HF-LVAD-myocytes compared with the HF-myocytes
(P<0.05). The HF-LVAD-myocytes had larger contractions
than the HF-myocytes at all frequencies of stimulation tested. The
negative force-frequency relationship of the HF-myocytes was improved
in HF-LVAD-myocytes but was not reversed. Responses to ß-adrenergic
stimulation (by isoproterenol) were greater in HF-LVAD-myocytes versus
HF-myocytes.
Conclusions—The results of the study strongly support the idea
that circulatory support with an LVAD improves myocyte contractile
properties and increases ß-adrenergic responsiveness.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Myocyte Recovery After Mechanical Circulatory Support in Humans With End-Stage Heart Failure
Key Words: heart-assist device • myocytes • cardiomyopathy • calcium
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P. Razeghi, M. Mukhopadhyay, T. J. Myers, J. N. Williams, C. S. Moravec, O. H. Frazier, and H. Taegtmeyer Myocardial tumor necrosis factor-{alpha} expression does not correlate with clinical indices of heart failure in patients on left ventricular assist device support Ann. Thorac. Surg., December 1, 2001; 72(6): 2044 - 2050. [Abstract] [Full Text] [PDF]
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J. D. Harding, V. Piacentino III, J. P. Gaughan, S. R. Houser, and K. B. Margulies Electrophysiological Alterations After Mechanical Circulatory Support in Patients With Advanced Cardiac Failure Circulation, September 11, 2001; 104(11): 1241 - 1247. [Abstract] [Full Text] [PDF]
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D. L. Mann and H. Taegtmeyer Dynamic Regulation of the Extracellular Matrix After Mechanical Unloading of the Failing Human Heart: Recovering the Missing Link in Left Ventricular Remodeling Circulation, September 4, 2001; 104(10): 1089 - 1091. [Full Text] [PDF]
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D. C. Welsh, K. Dipla, P. H. McNulty, A. Mu, K. M. Ojamaa, I. Klein, S. R. Houser, and K. B. Margulies Preserved contractile function despite atrophic remodeling in unloaded rat hearts Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1131 - H1136. [Abstract] [Full Text] [PDF]
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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]
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M. L. Ogletree-Hughes, L. B. Stull, W. E. Sweet, N. G. Smedira, P. M. McCarthy, and C. S. Moravec Mechanical Unloading Restores {beta}-Adrenergic Responsiveness and Reverses Receptor Downregulation in the Failing Human Heart Circulation, August 21, 2001; 104(8): 881 - 886. [Abstract] [Full Text] [PDF]
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A. Barbone, J. W. Holmes, P. M. Heerdt, A. H.S. The', Y. Naka, N. Joshi, M. Daines, A. R. Marks, M. C. Oz, and D. Burkhoff Comparison of Right and Left Ventricular Responses to Left Ventricular Assist Device Support in Patients With Severe Heart Failure: A Primary Role of Mechanical Unloading Underlying Reverse Remodeling Circulation, August 7, 2001; 104(6): 670 - 675. [Abstract] [Full Text] [PDF]
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J. D. Madigan, A. Barbone, A. F. Choudhri, D. L. S. Morales, B. Cai, M. C. Oz, and D. Burkhoff Time course of reverse remodeling of the left ventricle during support with a left ventricular assist device J. Thorac. Cardiovasc. Surg., May 1, 2001; 121(5): 902 - 908. [Abstract] [Full Text] [PDF]
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S. C. Stamou and P. J. Corso Coronary revascularization without cardiopulmonary bypass in high-risk patients: a route to the future Ann. Thorac. Surg., March 1, 2001; 71(3): 1056 - 1061. [Abstract] [Full Text] [PDF]
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A. C. Nicolosi, C. S. Kwok, S. J. Contney, G. N. Olinger, and Z. J. Bosnjak Gadolinium prevents stretch-mediated contractile dysfunction in isolated papillary muscles Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1122 - H1128. [Abstract] [Full Text] [PDF]
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L. E. Samuels, E. C. Holmes, M. P. Thomas, J. C. Entwistle III, R. J. Morris, J. Narula, and A. S. Wechsler Management of acute cardiac failure with mechanical assist: experience with the ABIOMED BVS 5000 Ann. Thorac. Surg., March 1, 2001; 71 (2007): S67 - S72. [Abstract] [Full Text] [PDF]
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K. Shirota, O. Kawaguchi, Y. Huang, T. Yuasa, R. Carrington, P. W. Brady, and S. N. Hunyor Ventricular remodeling after cardiomyoplasty in heart failure sheep: passive and dynamic effects Ann. Thorac. Surg., December 1, 2000; 70(6): 2102 - 2106. [Abstract] [Full Text] [PDF]
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P. M. Heerdt, J. W. Holmes, B. Cai, A. Barbone, J. D. Madigan, S. Reiken, D. L. Lee, M. C. Oz, A. R. Marks, and D. Burkhoff Chronic Unloading by Left Ventricular Assist Device Reverses Contractile Dysfunction and Alters Gene Expression in End-Stage Heart Failure Circulation, November 28, 2000; 102(22): 2713 - 2719. [Abstract] [Full Text] [PDF]
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A. M. Feldman and D. McNamara Myocarditis N. Engl. J. Med., November 9, 2000; 343(19): 1388 - 1398. [Full Text] [PDF]
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C. Piper, J. Bilger, E.-M. Henrichs, H.-P. Schultheiss, D. Horstkotte, and A. Doerner Is myocardial Na+/Ca2+ exchanger transcription a marker for different stages of myocardial dysfunction? Quantitative polymerase chain reaction of the messenger RNA in endomyocardial biopsies of patients with heart failure J. Am. Coll. Cardiol., July 1, 2000; 36(1): 233 - 241. [Abstract] [Full Text] [PDF]
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G. Olivetti, E. Cigola, R. Maestri, C. Lagrasta, D. Corradi, and F. Quaini Recent advances in cardiac hypertrophy Cardiovasc Res, January 1, 2000; 45(1): 68 - 75. [Full Text] [PDF]
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R. Houel, E. Vermes, D. B. Tixier, P. Le Besnerais, N. Benhaiem-Sigaux, and D. Y. Loisance Myocardial recovery after mechanical support for acute myocarditis: is sustained recovery predictable? Ann. Thorac. Surg., December 1, 1999; 68(6): 2177 - 2180. [Abstract] [Full Text] [PDF]
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D. L. Mann Mechanisms and Models in Heart Failure : A Combinatorial Approach Circulation, August 31, 1999; 100(9): 999 - 1008. [Full Text] [PDF]
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L. A. Soloff, K. B. Margulies, K. Dipla, J. A. Mattiello, S. R. Houser, and V. Jeevanandam Atrophy of Myocardium and Its Myocytes by Left Ventricular Assist Device • Response Circulation, August 31, 1999; 100 (9): 1011 - 1015. [Full Text] [PDF]
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K. Dipla, J. A. Mattiello, K. B. Margulies, V. Jeevanandam, and S. R. Houser The Sarcoplasmic Reticulum and the Na+/Ca2+ Exchanger Both Contribute to the Ca2+ Transient of Failing Human Ventricular Myocytes Circ. Res., March 5, 1999; 84(4): 435 - 444. [Abstract] [Full Text] [PDF]
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P. C. Simpson ß-Protein Kinase C and Hypertrophic Signaling in Human Heart Failure Circulation, January 26, 1999; 99(3): 334 - 337. [Full Text] [PDF]
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W. H. Barry Load-Dependent Myocyte Dysfunction Circulation, June 16, 1998; 97(23): 2297 - 2298. [Full Text] [PDF]
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K. Tobita, E. A. Schroder, J. P. Tinney, J. B. Garrison, and B. B. Keller Regional passive ventricular stress-strain relations during development of altered loads in chick embryo Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2386 - H2396. [Abstract] [Full Text] [PDF]
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Z. Yang and D. S Steele Effects of phosphocreatine on SR Ca2+ regulation in isolated saponin-permeabilized rat cardiac myocytes J. Physiol., March 15, 2002; 539(3): 767 - 777. [Abstract] [Full Text] [PDF]
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V. Piacentino III, J. P. Gaughan, and S. R. Houser L-Type Ca2+ Currents Overlapping Threshold Na+ Currents: Could They Be Responsible for the "Slip-Mode" Phenomenon in Cardiac Myocytes? Circ. Res., March 8, 2002; 90(4): 435 - 442. [Abstract] [Full Text] [PDF]
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