First clinical trial with etomoxir in patients with chronic congestive heart failure

Clinical Science

Volumn 99, Issue 1, 2000, Pages 27-35

  Schmidt Schweda, Stephan ^a   Holubarsch, Christian ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

Author keywords

Congestive heart failure; Etomoxir; Phenotype; Sarcoplasmic reticulum Ca2+ ATPase

Indexed keywords

ADENOSINE TRIPHOSPHATASE (CALCIUM); BETA ADRENERGIC RECEPTOR BLOCKING AGENT; DIGOXIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; ETOMOXIR; MYOSIN HEAVY CHAIN;

ADULT; AGED; ARTERY CATHETER; ARTICLE; BICYCLE ERGOMETER; CLINICAL ARTICLE; CLINICAL TRIAL; CONGESTIVE HEART FAILURE; ECHOCARDIOGRAPHY; EXERCISE; GENE EXPRESSION; HEART DILATATION; HEART FUNCTION; HEART HEMODYNAMICS; HEART LEFT VENTRICLE EJECTION FRACTION; HEART OUTPUT; HEART RATE; HEART STROKE VOLUME; HUMAN; HUMAN TISSUE; INOTROPISM; ISCHEMIC HEART DISEASE; MALE; PRIORITY JOURNAL; SARCOPLASMIC RETICULUM; SIDE EFFECT; VASODILATATION;

EID: 0033910352     PISSN: 01435221     EISSN: None     Source Type: Journal    
DOI: 10.1042/cs0990027     Document Type: Article

References (67)

1. 1 Briggs, F. N., Wise, R. M. and Feher, J. J, (1983) Diagnosis of alterations in sarcoplasmic reticulum function. In Myocardial Hypertrophy and Failure (Alpert, N. R., ed.), pp. 513-525, Raven Press, New York
2. 2 Limas, C. J., Okivan, M., Goldenberg, J. F., Levine, T. B., Bendit, B. G. and Simon, A. (1987) Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy. Cardiovasc. Res. 21, 601-605
3. 2+-ATPase gene expression in the human ventricle during end-stage heart failure. J. Clin. Invest. 85, 305-309
4. 2+-ATPase gene in pressure overload induced cardiac hypertrophy in the rat. Circ. Res. 66, 554-564
5. 5 Schwartz, K., Carrier, L., Mercadier, J. J., Lompre, A. M. and Boheler, K. R. (1993) Molecular phenotype of the hypertrophied and failing myocardium. Circulation 87 (Suppl. 7), 5-10
6. 6 Arai, M., Matsui, H. and Periasamy, M. (1994) Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure. Circ. Res. 74, 555-564
7. 2+-ATPase and phospholamban mRNA expression in response to pressure overload and thyroid hormone. Proc. Natl. Acad. Sci. U.S.A. 86, 2966-2970
8. 8 Schwartz, K., Carrier, L., Lompre, A. M., Mercadier, J. J. and Boheler, K. R. (1992) Contractile proteins and sarcoplasmic reticulum calcium-ATPase gene expression in the hypertrophied and failing heart. Basic Res. Cardiol. 87 (Suppl. 1), 285-290
9. 9 Izumo, S., Lompre, A. M., Matsuoka, R. et al. (1987) Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy. J. Clin. Invest. 79, 970-977
10. 10 Jacob, R., Ebrecht, G., Holubarsch, Ch., Rupp, H. and Kissling, G. (1983) Mechanics and energetics in cardiac hypertrophy as related to the isoenzyme pattern of myosin. In Myocardial Hypertrophy and Failure (Alpert, N. R., ed.), pp. 533-569, Raven Press, New York
11. 11 Holubarsch, Ch., Litten, R. Z., Mulieri, L. A. and Alpert, N. R. (1985) Energetic changes of myocardium as an adaptation to chronic hemodynamic overload and thyroid gland activity. Basic Res. Cardiol. 80, 582-593
12. 12 Lowes, B., Minobe, W., Abraham, W. T. et al. (1997) Changes in gene expression in the intact human heart. Downregulation of α-myosin heavy chain in hypertrophied, failing myocardium. J. Clin. Invest. 100, 2315-2324
13. 13 Nakao, K., Minobe, W., Roden, R., Bristow, M. R. and Leinwand, L. A. (1997) Myosin heavy chain gene expression in human heart failure. J. Clin. Invest. 100, 2370-2372
14. 14 de Tombe, P. (1998) Congestive heart failure: role of cross-bridge cycle kinetics. Cardiovasc. Res. 40, 440-443
15. 15 Gwathmey, J. K., Copelas, L., Mackinnon, R. et al. (1987) Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ. Res. 61, 70-76
16. 16 Gwathmey, J. K., Slawsky, M. T., Hajjar, R. J., Briggs, G. M. and Morgan, J. P. (1990) Role of intracellular calcium handling in force interval relationship of human ventricular myocardium. J. Clin. Invest. 85, 1599-1613
17. 17 Morgan, J. P. (1991) Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. N. Engl. J. Med. 325, 625-632
18. 18 Feldman, M. D., Gwathmey, J. K., Phillips, P., Schoen, F. and Morgan, J. P. (1998) Reversal of the force-frequency relationship in working myocardium from patients with end-stage heart failure. J. Appl. Cardiol. 3, 273-283
19. 19 Mulieri, L. A., Hasenfuss, G., Ittleman, F. et al. (1992) Altered myocardial force-frequency relation in human heart failure. Circulation 85, 1743-1750
20. 20 Pieske, B., Hasenfuss, G., Holubarsch, Ch., Schwinger, R., Böhm, M. and Just, H. (1992) Alterations of the force-frequency relationship in the failing human heart depend on underlying cardiac disease. Basic Res. Cardiol. 87 (Suppl. 1), 213-221
21. 2+-ATPase in failing and nonfailing human myocardium. Circ. Res. 75, 434-442
22. 22 Holubarsch, Ch., Schneider, R., Pieske, B. et al. (1995) Positive and negative inotropic effects of DL-Sotalol and D-Sotalol in failing and nonfailing human myocardium under physiological experimental conditions. Circulation 92, 2904-2910
23. 23 Pieske, B., Kretschmann, B., Meyer, M. et al. (1995) Alterations in intracellular calcium handling associated with the inverse force-frequency relation in human dilated cardiomyopathy. Circulation 92, 1169-1178
24. 24 Alpert, N. R. and Mulieri, L. A. (1983) Thermomechanical economy of hypertrophied hearts. Perspect. Cardiovasc. Res. 7, 619-630
25. 25 Jacob, R., Ebrecht, G., Holubarsch, Ch., Rupp, H. and Kissling, G. (1983) Mechanics and energetics in cardiac hypertrophy as related to the isoenzyme pattern of myosin. Perspect. Cardiovasc. Res. 7, 533-569
26. 26 Hasenfuss, G., Mulieri, L. A., Leavitt, J. B., Allen, P. D., Haeberle, J. R. and Alpert, N. R. (1992) Alteration of contractile function and excitation-contraction coupling in dilated cardiomyopathy. Circ. Res. 70, 1225-1232
27. 27 Ruf, Th., Schulte-Baukloh, H., Ludemann, J. et al. (1998) Alterations of cross-bridge kinetics in human atrial and ventricular myocardium. Cardiovas. Res. 40, 580-590
28. 28 Hoh, J. F. Y., McGrath, P. A. and Hale, P. T. (1977) Electrophoretic analysis of multiple forms of rat cardiac myosin : effects of hypophysectomy and thyroxme replacement. J. Mol. Cell. Cardiol. 10, 1053-1076
29. 29 Holubarsch, Ch., Goulette, R. P., Litten, R. Z., Marti, B. J., Mulieri, L. A. and Alpert, N. R. (1985) The economy of isometric force development, myosin isoenzyme pattern and myofibrillar ATPase activity in normal and hypothyroid rat myocardium. Circ. Res. 56, 78-86
30. 2+-ATPase in the rat heart. J. Biol. Chem. 263, 6491-6493
31. 31 Arai, M., Otsu, K., MacLennan, D. H., Alpert, N. R. and Periasamy, M. (1991) Effect of thyroid hormone on the expression of messenger RNA encoding sarcoplasmic reticulum proteins. Circ. Res. 69, 266-276
32. 32 Dillmann, W. H. (1986) Diabetes mellitus and hypothyroidism induce changes in myosin distribution in the rat heart - do alterations in fuel flux mediate these changes? Adv. Exp. Med. Biol. 194, 469-479
33. 33 Dillmann, W. H. (1991) Diabetes-induced changes in specific proteins and mRNA in the rat heart. In The Diabetic Heart (Nagano, M. and Dhalla, N. S., eds.), pp. 263-279, Raven Press, New York
34. 2+-pump ATPase of the diabetic rat heart by lipid-lowering intervention. Mol. Cell. Biochem. 132, 69-80
35. 35 McGarry, J. D., Woeltje, K. F., Kuwajima, M. and Foster, D. W. (1989) Regulation of ketogenesis and the renaissance of carnitine palmitoyltransferase. Diabetes 39, 271-284
36. 36 Wolf, H. P. O. and Engel, D. (1985) Decrease of fatty acid oxidation, ketogenesis and gluconcogenesis in isolated perfused rat liver by phenyl alkyl oxirane carboxylate (B807-27) due to inhibition of CPTI. Eur. J. Biochem. 146, 359-363
37. 37 Bartlett, K., Turnball, D. M. and Sherratt, H. S. A. (1984) Inhibition of hepatic and skeletal-muscle carnitine palmitoyltransferase I by 2-[5-(4-chlorophenyl)pentyl]-oxirane-2-carboxyl-CoA. Biochem. Soc. Trans. 12, 688-689
38. 38 Turnball, D. M., Bartlett, K., Younau, S. I. M. and Sherratt, II. S. A. (1984) The effect of 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxyl-CoA on mitochondrial oxidations. Biochem. Pharmacol. 33, 475-481
39. 39 Wolf, H. P. O. (1990) Aryl-substituted 2-oxirane carboxylic acids: a new group of antidiabetic drugs. In New Antidiabetic Drugs (Bailey, C. J. and Flatt, P., eds), pp. 217-229, Smith-Gordon Company Ltd, London
40. 40 Vetter, R. and Rupp, H. (1994) CPT-1 inhibition by ctomoxir has a chamber-related action on cardiac sarcoplasmic reticulum and isomyosins. Am. J. Physiol. 267, H2091-H2099
41. 41 Vetter, R., Kott, M. and Rupp, H. (1995) Differential influences of carnitine palmitoyltransferase-1 inhibition and hyperthyroldism on cardiac growth and sarcoplasmic reticulum phosphorylation. Eur. Heart J. 16 (Suppl. C), 15-19
42. 42 Rupp, H., Schulze, W. and Vetter, R. (1995) Dietary medium-chain triglycerides can prevent changes in myosin and SR due to CPT-1 inhibition by etomoxir. Am. J. Physiol. 269, R630-R640
43. 43 Rupp, H., Elimban, V. and Dhalla, N. S. (1992) Modification of subcellular organelles in pressure-overloaded heart by etomoxir, a carnitine palmitoyltransferase I inhibitor. FASEB. J. 6, 2349-2353
44. 44 Zarain-Herzberg, A., Rupp, H., Elimban, V. and Dhalla, N. S. (1996) Modification of sarcoplasmic reticulum gene expression in pressure overload cardiac hypertrophy by etomoxir. FASEB. J. 10, 1303-1309
45. 45 Haupt, E., Bliesath, H., Hoppe, F. U., Lühmann, R., Wolf, H. P. O. and Radke, H. W. (1988) Treatment of type 2 diabetic patients (NIDDM) with different dosages of etomoxir: a placebo controlled drf-study. Diabetes Res. Clin. Pract. 5, 615
46. 46 Lacher, F., Bachmann, W., Oerter, E. et al. (1990) Studie zur Wirksamkeit und Verträglichkeit von Etomoxir bei Typ-2-Diabetikern. Akt. Endokr. Stoffw. 11, 112
47. 47 Holubarsch, C., Hasenfuss, G., Schmidt-Schweda, S. et al. (1993) Angiotensin I and II exerts inotropic effects in atrial but not in ventricular human myocardium: an in vitro study under physiological experimental conditions. Circulation 88, 1228-1237
48. 48 Holubarsch, C., Ruf, T., Goldstein, D. J. et al. (1996) Existence of the Frank-Starling mechanism in the failing human heart. Investigations on the organ, tissue, and sarcomere levels. Circulation 94, 683-689
49. 49 Mulieri, L. A., Hasenfuss, G., Ittlman, F., Blanchard, E. M. and Alpert, N. R. (1989) Protection of left ventricular myocardium from cutting injury with 2,3-butanedione monoxime. Circ. Res. 65, 1441-1444
50. 2+-ATPase gene. Circ. Res. 71, 9-17
51. 51 Morita, E., Yasue, H., Yoshimura, M. et al. (1995) Increased plasma levels of brain natriuretic peptide in patients with acute myocardial infarction. Circulation 88, 82-91
52. 52 Hama, N., Itoh, H., Shirakama, G. et al. (1995) Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction. Circulation 92, 1558-1564
53. 53 Wiese, S., Radicke, D., Berger, T., Schmidt-Schweda, S., Füchtbauer, E. M. and Just, H. (1997) Gene expression of brain natriuretic peptide in human aerial preparations. Influence of muscle fiber length and angiotensin II. Eur. Heart J. 18 (Suppl.), 1890
54. 54 Nakao, K., Saito, Y., Itoh, H. et al. (1996) Roles of natriuretic peptides in heart failure. J. Cardiac Failure 2, 129-133
55. 55 Alpert, N. R. and Mulieri, L. A. (1982) Increased myothermal economy of isometric force generation in compensated cardiac hypertrophy induced by pulmonary-artery constriction in rabbit. A characterization of heat liberation in normal and hypertrophied right ventricular papillary muscle. Circ. Res. 50, 491-500
56. 56 Holubarsch, Ch., Litten, R. Z., Mulieri, L. A. and Alpert, N. R. (1985) Energetic changes of myocardium as an adaptation to chronic hemodynamic overload and thyroid gland activity. Basic Res. Cardiol. 80, 582-593
57. 57 Holubarsch, Ch., Goulette, R. P., Litten, R. Z., Martin, B. J., Mulieri, L. A. and Alpert, N. R. (1985) The economy of isometric force development, myosin isoenzyme pattern and myofibrillar ATPase activity in normal and hypothyroid rat myocardium. Circ. Res. 56, 78-86
58. 58 Hasenfuss, G., Mulieri, L. A., Blanchard, E. M. et al. (1991) Energetics of isometric force development in control and volume-overload human myocardium. Comparison with animal species. Circ. Res. 68, 836-846
59. 3 myosin isoenzyme ratio. J. Mol. Cell. Cardiol. 20, 679-687
60. 60 Feldmann, A. M., Weinberg, E. O., Ray, P. E. and Lorell, B. H. (1993) Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding. Circ. Res. 73, 184-192
61. 61 Hajjar, R. J., Kang, J. X., Gwathmey, J. K. and Rosenzweig, A. (1996) Physiological effects of adenoviral gene transfer of sarcoplasmic reticulum calcium ATPase in isolated rat myocytes. Circulation 94 (Suppl. I), 89
62. 62 Hajjar, R. J., Kang, J. X., Gwathmey, J. K. and Rosenzweig, A. (1997) Physiological effects of adenoviral gene transfer of sarcoplasmic reticulum calcium ATPase in isolated rat myocytes. Circulation 95, 423-429
63. 2+-ATPase overexpression by adenovirus mediated gene transfer and in transgenic animals. Cardiovasc. Res. 37, 360-366
64. 64 Fazio, S., Sabatini, D., Capaldo, B. et al. (1996) A preliminary study of growth hormone in the treatment of dilated cardiomyopathy. N. Engl. J. Med. 334, 809-814
65. 65 Turcani, M. and Rupp, H. (1997) Etomoxir improves left ventricular performance of pressure-overloaded rat heart. Circulation 96, 3681-3686
66. 66 Lopaschuk, G. D., Spaffort, M. A., Davies, N. J. and Wall, S. R. (1990) Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia. Circ. Res. 66, 546-553
67. 67 Kennedy, J. A., Unger, S. A. and Horrowitz, D. (1996) Inhibition of carnitine palmitoyltransferase-1 in rat heart and liver by perhexiline and amiodarone. Biochem. Pharmacol. 52, 273-280