The Time Course of Formation Of Systolic Dysfunction of the Heart in Doxorubicin Cardiomyopathy

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.