Endothelins: a Possible Mechanism of Cytostatics-induced Cardiomyopathy

Abstract

Endothelium responds to physical and chemical stimuli by synthesis and release of a variety of vasoactive and signal molecules. Cardiac performance is regulated by cardiac endothelial cells in a paracrine manner, analogous to vascular endothelial control of vascular tone. Endothelin-1 (ET-1), one of the most potent vasoconstrictor peptides, which is synthetized and released by endothelial cells. The role of ET-1 in some special pathological state is still unclear. Authors have investigated the effect of anthracyclines (maximal dose: 450 mg/bodysurface m²) on left ventricular systolic and diastolic function and on the level of plasma ET-1, in 31 (13 male, aged 19 – 70 years, mean: 38.9) patients suffered from Hodgkin (24) and Non-Hodgkin (7) lymphomas. They have also studied the association between plasma ET-1 concentration and echocardiographic parameters. Serum ET-1 was measured by ELISA method. Left ventricular function analyzed by echocardiography: ejection fraction (EF), time velocity integral (VTI), E and A waves, E/A ratio, deceleration time (DT), Doppler index were assessed. Statistical analysis was made by the Wilcoxon rank test. ET-1 plasma level decreased significantly after therapy (5.6 ± 3.5 vs. 3.1 ± 0.9 pg/ml, P < 0.0006). EF (56.4 ± 5.0% vs. 48.7 ± 5.1%, P < 0.0001) decreased, and DT (168.1 ± 36.8 ms vs. 206.5 ± 58.8 ms, P < 0.0073) increased significantly after administration of anthracycline, showing that both systolic and diastolic left ventricular performance was deteriorated. There was no difference in other echocardiographic parameters before and after therapy. In conclusion, decrease of serum ET-1 concentration might be a result of anthracyclin's direct cytotoxic effect and the decreasing level of ET-1 may play a role in the reduction of the EF. More studies are needed to evaluate the presence and severity of endothelial damage, and long-term follow-up may reveal the importance of low ET-1 level and may show the time is needed for the restoration of the ET-1 concentration to the basic level after cessation of cytostatic therapy.

• Endothelin-1
• Anthracyclines
• Cardiomyopathy
• Echocardiography
• Ventricular function