Adamcova Michaela, Lencova-Popelova Olga, Jirkovsky Eduard, Mazurova Yvona, Palicka Vladimir, Simko Fedor, Gersl Vladimir, Sterba Martin
Department of Physiology, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, Hradec Králové 500 38, Czech Republic.
Department of Pharmacology, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, Hradec Králové 500 38, Czech Republic.
Int J Cardiol. 2015 Dec 15;201:358-67. doi: 10.1016/j.ijcard.2015.07.103. Epub 2015 Aug 4.
Cardiac troponins (cTns) seem to be more sensitive for the detection of anthracycline cardiotoxicity than the currently recommended method of monitoring LV systolic function. However, the optimal timing of blood sampling remains unknown. Hence, the aims of the present study were to determine the precise diagnostic window for cTns during the development of chronic anthracycline cardiotoxicity and to evaluate their predictive value.
Cardiotoxicity was induced in rabbits with daunorubicin (3mg/kg, weekly, for 8 weeks). Blood samples were collected 2-168 h after the 1st, 5th and 8th drug administrations, and concentrations of cTns were determined using highly sensitive assays: hs cTnT (Roche) and hs cTnI (Abbott).
The plasma levels of cTns progressively increased with the rising number of chemotherapy cycles. While only a mild non-significant increase in both cTn levels occurred after the first daunorubicin dose, a significant rise was observed after the 5th and 8th administrations. Two hours after these administrations, a significant increase occurred with a peak between 4-6h and a decline until 24h. Discrete cTn release continued even after cessation of the therapy. While greater variability of cTn levels was observed around the peak concentrations, the values did not correspond well with the severity of LV systolic dysfunction. Unlike AMI in cardiotoxicity, cTn elevations may be better associated with cumulative dose and concentrations at steady state than cmax.
To the best of our knowledge, this is the first study to precisely describe the diagnostic window and predictive value of cTns in anthracycline cardiotoxicity.
与目前推荐的监测左心室收缩功能的方法相比，心肌肌钙蛋白（cTn）对检测蒽环类药物心脏毒性似乎更为敏感。然而，血样采集的最佳时间仍不清楚。因此，本研究的目的是确定慢性蒽环类药物心脏毒性发生过程中cTn的精确诊断窗口，并评估其预测价值。
用柔红霉素（3mg/kg，每周一次，共8周）诱导家兔产生心脏毒性。在第1次、第5次和第8次给药后2 - 168小时采集血样，使用高灵敏度检测方法测定cTn浓度：高敏肌钙蛋白T（罗氏）和高敏肌钙蛋白I（雅培）。
随着化疗周期数的增加，cTn的血浆水平逐渐升高。虽然第一次柔红霉素给药后两种cTn水平仅出现轻微的无显著意义的升高，但在第5次和第8次给药后观察到显著升高。在这些给药后2小时，出现显著升高，在4 - 6小时达到峰值，直至24小时下降。即使在治疗停止后，仍有离散的cTn释放。虽然在峰值浓度附近观察到cTn水平有更大的变异性，但这些值与左心室收缩功能障碍的严重程度并不十分相符。与心脏毒性中的急性心肌梗死不同，cTn升高可能与累积剂量和稳态浓度比峰浓度更相关。
据我们所知，这是第一项精确描述cTn在蒽环类药物心脏毒性中的诊断窗口和预测价值的研究。
