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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2024; 70(1): 3-13


M.V. Denysova, N.A. Strutynska, Yu.P. Korkach, L.A. Mys, O.M. Magomedov, R.B. Strutynskyi, V.F. Sagach

    Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine


Arrhythmias and congestive heart failure, which pose the greatest risk of toxic cardiomyopathy, are the clinically limiting side effects of doxorubicin, the main highly active anticancer agent. The difficulty of early diagnosis of cardiomyopathy and timely detection of cardiac dysfunction associated with chemotherapy remains a significant medical problem. The aim of our study was to identify early signs of acute doxorubicin-induced cardiotoxicity in adult rats by assessing ECG changes and biochemical parameters. Acute cardiotoxicity was modelled by short-term intraperitoneal injection of doxorubicin at a total dose of 15 mg/kg. On the 5th day of the experiment, visual fluctuations of electrocardiogram (ECG) waveforms, duration and amplitude of the main teeth and intervals, as well as heart rate (HR) in the control and experimental groups of rats were studied to determine early ECG signs of cardiotoxicity. The most significant ECG changes were a doubling of the QT interval duration and significant ST-segment elevation in the rats of the experimental group. In experiments on isolated aortic rings, we demonstrated doxorubicin-induced disruption of both vascular relaxation and contraction mechanisms. The endothelium-dependent relaxation of vascular preparations of animals after administration of doxorubicin to acetylcholine (0.1 μmol/l) was 47% less than in the control group. The vascular ring contractions in rats under the influence of norepinephrine (10 μmol/l) were 59% lower than in control rats. After doxorubicin administration, oxidative stress developed against the background of cardiovascular disorders. Thus, the content of diene conjugates and malondialdehyde increased by 4 and 2.5 times, respectively. At the same time, in isolated cardiac mitochondria, the activity of inducible NO synthase increased 3.7-fold with a simultaneous significant 4.8-fold inhibition of constitutive NO synthase. An increase in the content of acute-phase biochemical parameters that are markers of damage, namely alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatine phosphokinase myocardial fraction (CPK MB) by 2.2, 1.4 and 1.5 times, respectively, was detected. Thus, the acute cardiotoxic effect of doxorubicin results in changes in the systolic-diastolic function of the left ventricle of the heart and its conduction, automaticity and contractility, as well as impaired relaxation and contraction of isolated preparations of the aorta against the background of increased activity of inducible and decreased constitutive NO synthesis, accompanied by oxidative stress and increased content of biochemical markers of myocardial damage.

Keywords: doxorubicin; electrocardiogram; vascular reactions; oxidative stress; NO-synthases; markers of myocardial damage.


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