Abstract
Purpose
Cardiac troponin T (cTnT) plasma concentration is considered a useful marker of anthracycline-induced cardiomyopathy. In this study we used daunorubicin-treated Chinchilla rabbits as a model to investigate the relationship between left ventricular contractility and cTnT plasma concentrations.
Methods
Two groups of animals were used: a control group (n=8) received i.v. saline, and an experimental group (n=11) received daunorubicin (3 mg/kg, i.v.). The substances were administered once weekly for 10 weeks, and 5–7 days after the last administration, left ventricular cardiac contractility (dP/dtmax) was invasively measured as a contractility index and blood was sampled for cTnT concentration determination (Elecsys Troponin T STAT immunoassay).
Results
Cardiac contractility was significantly lower in seven surviving daunorubicin-treated animals than in control animals (745.7±69.3 vs 1393.4±25.5 kPa/s; P<0.001), while cTnT plasma concentrations were significantly increased (medians 0.278 vs 0.000 ng/ml; P<0.001). When the dP/dtmax values of individual daunorubicin-treated animals were plotted against the corresponding cTnT plasma concentrations, a close negative linear correlation was found (R=−0.910; P<0.005; regression equation: dP/dtmax=−1861*cTnT+1234).
Conclusions
This study suggests that determination of cTnT plasma levels, which is simple and inexpensive, could be used in anthracycline-treated patients for left ventricular systolic function assessment and contractility estimation.
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References
Adamcova M, Gersl V, Hrdina R, Melka M, Mazurova Y, Vavrova J, Palicka V, Kokstein Z (1999) Cardiac troponin T as a marker of myocardial damage caused by antineoplastic drugs in rabbits. J Cancer Res Clin Oncol 125:268
Bertinchant JP, Polge A, Juan JM, Oliva-Lauraire MC, Giuliani I, Marty-Double C, Burdy JY, Fabbro-Peray P, Laprade M, Bali JP, Granier C, de la Coussaye JE, Dauzat M (2003) Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy in rats, and their relationship with echocardiographic and histological findings. Clin Chim Acta 329:39
Cardinale D, Sandri MT, Martinoni A, Tricca A, Civelli M, Lamatia G, Cinieri S, Martinelli G, Cipolla CM, Fiorentini C (2000) Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol 36:517
Cassidy SC, Chan DP, Rowland DG, Allen HD (1998) Effects of doxorubicin on diastolic function, contractile reserve, and ventricular-vascular coupling in piglets. Pediatr Cardiol 19:450
Della Torre P, Podesta A, Imondi AR, Moneta D, Sammartini U, Arrigoni C, Terron A, Brughera M (2001) PNU-159548, a novel cytotoxic antitumor agent with a low cardiotoxic potential. Cancer Chemother Pharmacol 47:355
Herman EH, Ferrans VJ (1998) Preclinical animal models of cardiac protection from anthracycline-induced cardiotoxicity. Semin Oncol 25 [4 Suppl 10]:15
Herman EH, Lipshultz SE, Rifai N, Zhang J, Papoian T, Yu ZX, Takeda K, Ferrans VJ (1998) Use of cardiac troponin T levels as an indicator of doxorubicin-induced cardiotoxicity. Cancer Res 58:195
Herman EH, Zhang J, Lipshultz SE, Rifai N, Chadwick D, Takeda K, Yu ZX, Ferrans VJ (1999) Correlation between serum levels of cardiac troponin-T and the severity of the chronic cardiomyopathy induced by doxorubicin. J Clin Oncol 17:2237
Herman EH, Zhang J, Rifai N, Lipshultz SE, Hasinoff BB, Chadwick DP, Knapton A, Chai J, Ferrans VJ (2001) The use of serum levels of cardiac troponin T to compare the protective activity of dexrazoxane against doxorubicin- and mitoxantrone-induced cardiotoxicity. Cancer Chemother Pharmacol 48:297
Hrdina R, Gersl V, Klimtova I, Simunek T, Machackova J, Adamcova M (2000) Anthracycline-induced cardiotoxicity. Acta Medica (Hradec Kralove) 43:75
Joint European Society of Cardiology/American College of Cardiology Committee (2000) Myocardial infarction redefined—a consensus document of the joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. J Am Coll Cardiol 36:959
Katus HA, Remppis A, Neumann FJ, Scheffold T, Diederich KH, Kubler W (1991) Diagnostic efficiency of troponin T measurements in acute myocardial infarction. Circulation 83:902
La Vecchia L, Mezzena G, Ometto R, Finocchi G, Bedogni F, Soffiati G, Vincenzi M (1997) Detectable serum troponin I in patients with heart failure of nonmyocardial ischemic origin. Am J Cardiol 80:88
Lipshultz SE, Rifai N, Sallan SE, Lipsitz SR, Dalton V, Sacks DB, Ottlinger ME (1997) Predictive value of cardiac troponin T in pediatric patients at risk for myocardial injury. Circulation 96:2641
Singal PK, Iliskovic N, Li T, Kumar D (1998) Adriamycin cardiomyopathy: pathophysiology and prevention. FASEB J 11:931
van der Laarse A (2002) Hypothesis: troponin degradation is one of the factors responsible for deterioration of left ventricular function in heart failure. Cardiovasc Res 56:8
Acknowledgements
The authors would like to thank Mrs. Ludmila Koželuhová and Mrs. Jiřina Hoffmanová for their skilful technical assistance during the study, and Assoc. Prof. Bohuslav Mánek for his kind revision of the English text. This study was supported by Grant GA CR no. 305/03/1511, and by Research Projects MSM 111500002 and CEZ J13/98:11600002.
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Šimůnek, T., Klimtová, I., Adamcová, M. et al. Cardiac troponin T as an indicator of reduced left ventricular contractility in experimental anthracycline-induced cardiomyopathy. Cancer Chemother Pharmacol 52, 431–434 (2003). https://doi.org/10.1007/s00280-003-0675-z
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DOI: https://doi.org/10.1007/s00280-003-0675-z