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.

The role of endothelin-1 (ET-1) in certain pathological states is still unclear. We have investigated the effect of anthracyclines (maximum dose, 450 mg/m(2) of body surface) on left ventricular systolic and diastolic function and how it influences the level of plasma ET-1 in 21 patients (12 female and nine male) with Hodgkin and non-Hodgkin lymphoma. We also studied the association between plasma ET-1 concentration and echocardiographic parameters. Serum ET-1 was measured by ELISA. Left ventricular function was analysed by echocardiography: ejection fraction (EF), velocity-time integral, E- and A-waves, E:A ratio, deceleration time (DT) and Doppler index were all measured. Statistical analysis was made by the Wilcoxon rank test. EF and serum ET-1 level decreased significantly (EF, 56.29+/-5.0% to 48.57+/-5.9%, P<0.0001; ET-1, 6.45+/-4.0 pg/ml to 2.9+/-1.0 pg/ml, P<0.0001). DT increased significantly (179.8+/-47.8 ms to 215.5+/-66.7 ms, P<0.01) after anthracycline therapy. There was no difference in other echocardiographic parameters before and after therapy. The decrease in serum ET-1 concentration might be a result of anthracycline's direct cytotoxic effect and the decreasing level of ET-1 can play a role in the reduction of EF. However, more studies are needed to evaluate the presence and severity of endothelial damage.

Anthracyclines are widely used chemotherapeutic agents in the treatment of lymphomas known to induce cardiomyopathy in more than 20% of patients. There is increasing experimental evidence that cardiac endothelial cells regulate cardiac performance and that endothelin-1 (ET-1) is a central substance in this regulatory mechanism. Twenty (seven male, aged 20-68 years) patients with Hodgkin's or non-Hodgkin's lymphoma treated with anthracycline were followed-up for 1 year. At baseline, after cessation of anthracycline treatment and at 1 year, the plasma ET-1 level was measured by enzyme-linked immunosorbent assay and cardiac function was estimated by echocardiographic measurement of the ejection fraction, the E/A ratio and the deceleration time. The ET-1 level decreased significantly after therapy (5.47 +/- 3.34 pg/mL versus 3.44 +/- 0.69 pg/mL, P < 0.02), and remained significant at 1 year (3.43 +/- 0.57 pg/mL, P < 0.008). The ejection fraction (57.80 +/- 4.73% versus 48.05 +/- 5.65%, P < 0.0001) and the E/A ratio (1.35 +/- 0.40 versus 1.15 +/- 0.40, P < 0.01) decreased, and the deceleration time (177.00 +/- 44.96 ms versus 209.50 +/- 66.25 ms, P < 0.04) increased significantly after therapy, showing that both systolic and diastolic left ventricular performance were deteriorated. Compared with the baseline, the same significant changes were found at 1 year (ejection fraction, 50.65 +/- 8.87%, P < 0.0007; E/A ratio, 1.10 +/- 0.34, P < 0.003; deceleration time, 223.25 +/- 46.85 ms, P < 0.002). The decrease of the ET-1 concentration might be a result of anthracyclines' direct cytotoxic effect and the decreasing level of ET-1 may play a role in the ejection fraction reduction. The results of 1-year follow-up suggest that, although anthracycline toxicity occurs shortly after treatment, the undesirable effect remains.

No abstract