Lakomkin V L, Abramov A A, Gramovich V V, Vyborov O N, Lukoshkova E V, Ermishkin V V, Kapelko V I
Russian Cardiological Research and Productive Centre, Moscow, Russia.
Kardiologiia. 2017 Jan(1):59-64.
The anthracycline-induced cardiomyopathy is a frequent and menacing complication of antitumor therapy leading to chronic heart failure. A study of the formation of heart failure can reveal early signs of the development of systolic dysfunction of the heart. In this work in rats we studied cardiac function at different duration of doxorubicin treatment, the most effective anthracycline antibiotic. Cumulative doses of doxorubicin were 8-20 mg/kg, and the term of study lasted from 6 to 20 weeks. The echocardiography and catheterization of the left ventricle (LV) have been use. The ejection fraction and other indicators of LV contractility decreased steadily with increasing dose and duration of the study, in parallel with rat survival. However, the cardiac output related to the unit of body weight, as well as diastolic LV size, remained at a level close to control within 8-10 weeks. Only after 20 weeks when the ejection fraction decreased from 81+/-1 to 49+/-4%, diastolic LV volume increased by 59%. Invasive indicators of myocardial contractility and relaxability significantly decreased by 11 and 19% after doxorubicin dose of 8 mg/kg, while time of preejection and time of systole increased by 18 and 10%. These changes progressed with increasing doses of doxorubicin. At each dose, the relaxation constant declined relatively deeper than contractility index by 8-25%. The results show that: 1) the gradual formation of cardiac insufficiency mobilizes a variety of compensatory mechanisms that retard cardiac dilatation; 2) the development of systolic dysfunction takes place with a predominantly violation of relaxation process; 3) an elongation of the preejection period and duration of systole may serve as noninvasive criteria for the formation of the systolic dysfunction.
蒽环类药物所致心肌病是抗肿瘤治疗常见且危险的并发症，可导致慢性心力衰竭。对心力衰竭形成过程的研究能够揭示心脏收缩功能障碍发展的早期迹象。在本研究中，我们以大鼠为实验对象，研究了最有效的蒽环类抗生素阿霉素在不同治疗时长下对心脏功能的影响。阿霉素的累积剂量为8 - 20mg/kg，研究持续时间为6至20周。我们采用了超声心动图和左心室导管插入术。随着研究剂量和时长的增加，左心室射血分数及其他收缩性指标与大鼠存活率同步稳步下降。然而，单位体重的心输出量以及左心室舒张期大小在8 - 10周内维持在接近对照组的水平。仅在20周后，射血分数从81±1%降至49±4%，左心室舒张期容积增加了59%。在阿霉素剂量为8mg/kg时，心肌收缩性和舒张性指标分别显著下降了11%和19%，而射血前期和收缩期时间分别增加了18%和10%。这些变化随着阿霉素剂量的增加而加剧。在每个剂量下，舒张常数的下降相对收缩性指数更深，降幅为8 - 25%。结果表明：1）心脏功能不全的逐渐形成会调动多种代偿机制，从而延缓心脏扩张；2）收缩功能障碍的发展主要是由于舒张过程受损；3）射血前期延长和收缩期持续时间可作为收缩功能障碍形成的无创性标准。
