Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac, 34000, Serbia.
Department of General and Inorganic Chemistry, Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade, 11000, Serbia.
Mol Cell Biochem. 2019 Aug;458(1-2):89-98. doi: 10.1007/s11010-019-03533-8. Epub 2019 Apr 15.
The aim of the present study was to compare the cardiodynamic parameters in the isolated rat heart in animals chronically treated with cisplatin, platinum(IV) complex and its diamine ligand. Sixty Wistar albino rats (8 weeks old) were divided into five groups: three experimental and two control groups. Animals in all groups were treated with a dose of 4 mg/kg body weight once a week for 4 weeks with different substances; experimental groups received cisplatin, ligand and octahedral platinum(IV) complex, and control groups received saline and dimethyl sulfoxide. After sacrificing the animals, hearts were isolated and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cmHO). The following parameters of cardiac function were continuously recorded: maximum and minimum rate of change of pressure in the left ventricle, systolic and diastolic left ventricular pressure, heart rate and coronary flow. The results showed statistically significant differences between all experimental groups in maximum and minimum rate of pressure development as well as in systolic pressure of the left ventricle, whereas cisplatin, ligand and the platinum(IV) complex had effects on heart contractility without significant influences on coronary circulation. The findings of the present study could be important for a better understanding of anticancer drug cardiac side effects. Our results indicate that compared to cisplatin as a "gold standard", novel platinum complexes and ligands do not possess fewer negative effects on the heart, indicating insufficient safety for their usage in terms of affecting cardiac function, a result that can be of great interest for further investigations.
本研究的目的是比较慢性给予顺铂、铂（IV）配合物及其二胺配体的大鼠离体心脏的心动力学参数。60 只 Wistar 白化大鼠（8 周龄）分为五组：三组实验组和两组对照组。所有组的动物均每周接受 4mg/kg 体重的不同物质治疗 4 周；实验组接受顺铂、配体和八面体铂（IV）配合物，对照组接受生理盐水和二甲基亚砜。处死动物后，根据 Langendorff 技术分离心脏并在逐渐增加的冠状动脉灌注压（40-120cmHO）下进行灌注。连续记录以下心功能参数：左心室压力变化的最大和最小速率、左心室收缩压和舒张压、心率和冠状动脉流量。结果显示，所有实验组的最大和最小压力发展速率以及左心室收缩压均存在统计学差异，而顺铂、配体和铂（IV）配合物对心肌收缩力有影响，但对冠状动脉循环无显著影响。本研究的结果可能对更好地理解抗癌药物的心脏副作用很重要。我们的结果表明，与顺铂作为“金标准”相比，新型铂配合物和配体对心脏的负面影响并不少，这表明它们在影响心脏功能方面的安全性不足，这一结果可能对进一步的研究很有意义。
