Simůnek Tomás, Klimtová Ivona, Adamcová Michaela, Gersl Vladimír, Hrdina Radomír, Sterba Martin, Kaplanová Jana, Mazurová Yvona
Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
Cancer Chemother Pharmacol. 2003 Nov;52(5):431-4. doi: 10.1007/s00280-003-0675-z. Epub 2003 Jul 9.
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.
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).
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).
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.
心肌肌钙蛋白T(cTnT)血浆浓度被认为是蒽环类药物所致心肌病的一项有用标志物。在本研究中,我们使用柔红霉素处理的龙猫兔作为模型,来研究左心室收缩性与cTnT血浆浓度之间的关系。
使用两组动物:对照组(n = 8)静脉注射生理盐水,实验组(n = 11)静脉注射柔红霉素(3 mg/kg)。每周给药1次,共给药10周,在最后一次给药后5 - 7天,通过有创测量左心室心肌收缩性(dP/dtmax)作为收缩性指标,并采集血液样本用于测定cTnT浓度(电化学发光法检测肌钙蛋白T STAT免疫分析)。
7只存活的经柔红霉素处理的动物的心脏收缩性显著低于对照动物(745.7±69.3 vs 1393.4±25.5 kPa/s;P < 0.001),而cTnT血浆浓度显著升高(中位数分别为0.278 vs 0.000 ng/ml;P < 0.001)。当将经柔红霉素处理的各个动物的dP/dtmax值与相应的cTnT血浆浓度作图时,发现两者呈密切的负线性相关(R = -0.910;P < 0.005;回归方程:dP/dtmax = -1861*cTnT + 1234)。
本研究提示,cTnT血浆水平的测定简单且廉价,可用于蒽环类药物治疗患者的左心室收缩功能评估和收缩性估计。