Summary
An increased cytoplasmatic calcium levels seems to play an important role in the pathogenesis of Adriamycin (ADM)-induced cardiomyopathy. Experiments have shown that calcium channel blockers such as verapamil may prevent this type of cardiomyopathy in animals, but data are contradictory. In a clinical pilot trial, the left ventricular function of 22 patients undergoing ADM-chemotherapy in combination with verapamil was examined. M-mode echocardiograms were performed parallel to every chemotherapy course. Left ventricular function was determined by fractional shortening rate (FS) and peak fibre shortening velocity (Vcf max.). Three 40-mg doses of verapamil were given p.o./day continuously. Data of these patients were compared with a control group of 61 patients treated and checked equally without additional verapamil therapy. In the course of therapy parameters of left ventricular function remained almost constant in the verapamil group but decreased significantly in the control group. In the verapamil group FS changed by −0.05 FS %/100 mg ADM/m2, Vcf max. by +0.015 circ./s/ 100 mg ADM/m2 compared with −2.31 FS % and −0.33 circ./s in the control group (P 0.01 and 0.001, respectively). In the verapamil group no congestive heart failure occurred and no patient showed FS below 30%, whereas in the control group in 23% (14) of the cases ADM therapy had to be stopped because FS fell below 30%. One congestive heart failure was observed. These clinical results suggest that verapamil may be a useful drug for preventing ADM-induced cardiomyopathy but further investigations are necessary.
Similar content being viewed by others
Literatur
Alexander J, Dainiak N, Berger HJ, Goldmann L, Johnstone D, Reduto L, Duffy T, Schwartz P, Gottschalk A, Zaret BL (1979) Serial Assessment of Doxorubicin Cardiotoxicity with Quantitative Radionuclide Angiocardiography. N Engl J Med 300/6:278–283
Azuma J, Sperelakis N, Hasegawa H, Tanimoto T, Vogel S, Ogura K, Awata N, Sawamura A, Harada H, Ishiyama T, Morita Y, Yamamura Y (1981) Adriamycin cardiotoxicity: possible pathogenic mechanisms; J Mol Cell Cardiol 13:381–397
Bloom KR, Bini RM, Williams CM, Sonley MJ, Gribbin MA (1978) Echocardiography in Adriamycin Cardiotoxicity. Cancer 41:1265–1269
Bristow MR (1980) Anthracycline Cardiotoxicity. In: Bristow MR (ed) Drug induced Heart Disease, Elsevier/North-Holland Biomedical Press, Amsterdam, pp 192–215
Bühner R (1981) Kardiotoxizität von Adriamycin; Beiträge Onkologie, Vol 9, Karger, Basel, pp 33–42
Bühner R, Biedert S, Miura D (1980) Experimentelle Untersuchungen zur Klärung der Pathogenese der durch Adriamycin-induzierten Kardiomyopathie. Arzneim Forsch 30:1065–1070
Daniels JR, Billingham ME, Gelbart A, Bristow MR (1976) Effect of Verapamil and Propranolol on Adriamycin-Induced Cardiomyopathy in Rabbits. Circulation [Suppl II]:70
Deprez-De Campeneere D et al. (1982) Comparative Cardiac and Renal Toxicity of Daunorubicin in the Rat and Rabbit; Cancer Treatment Rep 66/2:395–397
Dresdale A, Bonow RO, Wesley R, Palmer ST, Barr L, Mathison D, D'Angelo T, Rosenberg SA (1983) Prospective Evaluation of Doxorubicin-Induced Cardiomyopathy Resulting from Postsurgical Adjuvant Treatment of Patients with Soft Tissue Sarcomas. Cancer 52:51–60
Ferrans VJ, Herman EH (1978) Cardiomyopathy Induced by Antineoplastic Drugs. In: Kaltenbach M, Loogen F, Olsen EGJ (ed) Cardiomyopathy and Myocardial Biopsy. Springer, Berlin Heidelberg New York, pp 12–26
Gottdiener JS, Mathisen DJ, Borer JS, Bonow RO, Myers CE, Barr LH, Schwartz DE, Bacharach SL, Green MV, Rosenberg SA (1981) Doxorubicin Cardiomyopathy: Assessment of Late Left Ventricular Dysfunction By Radionuclide Cineangiography. Ann Int Med 94/1:430–435
Hanrath P, Mathey DG, Kremer P, Sonntag F, Bleifeld W (1980) Effect of Verapamil on Left Ventricular Isovolumic Relaxation Time and Regional Left Ventricular Filling in Hypertrophic Cardiomyopathy. Am J Cardiol 45:1258–1263
Henderson IC, Frei III E (1979) Adriamycin and the Heart. N Engl J Med 300/6:310–311
Henderson IC, Frei III E (1980) Adriamycin Cardiotoxicity. Am Heart J 99/5:671–674
Klugmann S, Bartoli-Klugmann F, Decorti G, Gori D, Silvestri F, Camerini F (1981) Adriamycin Experimental Cardiomyopathy in Swiss Mice. Different Effect of Two Calcium Antagonistic Drugs on ADM-Induced Cardiomyopathy. Pharm Res Commun 13/8:769–776
Krebs W, Hanrath P, Bleifeld W, Effert S (1977) Rechnergestützte Auswertung von M-mode Echokardiogrammen. Herz-Kreislauf 9/9:519–525
Lefrak EA, Pitha J, Rosenheim S, O'Bryan RM, Burgess MA, Gottlieb JA (1975) Adriamycin Cardiomyopathy. Cancer Chemother Rep Part 3, 6:203–208
Lenaz L, Page JA (1976) Cardiotoxicity of Adriamycin and related Anthracyclines; Cancer Treatment Rev 3:111–120
Markiewicz W, Robinson E, Peled B, Kaufman S, Carter A (1980) Early Detection of Doxorubicin Cardiotoxicity by M-mode Echocardiography. Cancer Chemotherap Pharmacol 5/2:119–125
Minow RA, Benjamin BS, Gottlieb JA (1975) Adriamycin Cardiomyopathy — An Overview with Determination of Risk Factors. Cancer Chemother Rep Part 3, 6:195–201
Moor L, Landon EJ, Cooney DA (1977) Inhibition of the Cardiac Mitochondrial Calcium Pump by Adriamycin in Vitro. Biochem Med 18:131–138
Müllerleile U, Bieber KD, Garbrecht M, Hanrath P, Lüthje M (1981) Ergebnisse und klinische Bedeutung der echokar-diographischen Verlaufsbeobachtung bei Adriamycin-behandelten Patienten; Verhandlungen Dtsch Gesellschaft Innere Med Vol 87, S 1122–1124
Olson HM, Young DM, Prieur DJ, Le Roy AF, Reagan RL (1974) Amer J Path 77:439
Praga C et al. (1979) Adriamycin Cardiotoxicity: A Survey of 1273 Patients. Cancer Treatment Rep 63/5:827–834
Quinones MA, Gaasch WH, Alexander JC (1974) Echocardiographic assessment of left ventricular function. Circulation 50:42
Ritchie JL, Singer JW, Thorning D, Sorensen SG, Hamilton GW (1980) Anthracycline cardiotoxicity: clinical and pathologic outcomes assessed by radionuclide ejection fraction. Cancer 46:1109–1116
Stein E, Hanrath P, Bleifeld W, Garbrecht M, Müllerleile U, Salecker B (1978) Abnormes Kontraktions- und Füllverhalten des linken Ventrikels bei Tumorpatienten unter Adriamycin-Therapie. Dtsch Med Wochenschr 103:1408–1412
Tsuruo T, Iida H, Yamashiro M, Tsugagoshi S, Sakurai Y (1982) Enhancement of vincristine- and adriamycin-induced cytotoxicity by verapamil in P 388 leukemia and its sublines resistant to vincristine and adriamycin. Biochem Pharmacol 31:3138–3140
Wikman-Coffelt J, Rapcsak M, Sievers R, Rouleau JL, Parmley WW (1983) Verapamil, Propranolol, and hydralazine protect against the acute cardiac depression induced by adriamycin. Cardiovasc Res 17:43–49
Wrogemann K, Pena SDJ (1976) Mitochondrial Calcium Overload: A General Mechanism for Cell Necrosis in Muscle Diseases. Lancet I:672–673
Young DM, Mettler FP, Fioravanti JL (1976) Adriamycin, Verapamil and Calcium Metabolism. Proc Amer Ass Cancer Res 16/17:90
Author information
Authors and Affiliations
Additional information
Auszugsweise vorgetragen auf der 55. Jahrestagung der American Heart Association, Dallas, USA, 1982 sowie auf dem 13. International Cancer Congress, Seattle, USA, 1982
Mit Unterstützung der Deutschen Krebshilfe
Rights and permissions
About this article
Cite this article
Müllerleile, U., Garbrecht, M., Hanrath, P. et al. Mögliche Prävention der Adriamycin-induzierten Kardiomyopathie durch Verapamil. Klin Wochenschr 62, 1032–1037 (1984). https://doi.org/10.1007/BF01711726
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01711726