Abstract:
Background: The cardiotoxicity of doxorubicin (Dx), an antineoplastic drug, is imposed by the development of cardiomyopathy and heart failure.
The expression of endothelin-1 (ET-1) in myocardium under the action of Dx, directly correlates with the degree of cardiac dysfunction, mediated by
endothelin A (ETA) receptor.
Material and methods: For prospective randomized study 2 groups of white rats (experimental group n=9, control group n=9) were used. During 2
weeks in the control group was administrated Dx (i/p, 4mg/kg in one dose, twice/week), cumulative dose – 16 mg/kg. The ET-1 effects were estimated
at its peak action in concentration 10-7 M (mol), reproduced after 30 sec of endothelin stimulation.
Results: The functional parameters of isolated heart perfused in physiologic regime and in condition of volume and resistance overload under the ET-1
action in the group with Dx compared with the control one, were reduced considerably, namely: cardiac output (CO); left ventricle systolic pressure
(LVSP); left ventricle end-diastolic pressure (LVEDP).
Conclusions: Under the ET-1 action on the isolated heart perfused in physiologic regime in the group with Dx – the LVSP and CO were reduced determining
negative inotropic effect. At the volume overload test, under the ET-1 action, the diastolic impairment was more evident in the group with Dx, due to
increased LVEDP. At the resistance overload test under the ET-1 action, the CO was reduced indicating the depreciation of myocardial contraction capacity.
Description:
Department of Pathophysiology and Clinical Pathophysiology Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, the Republic of Moldova, The 75th anniversary of Nicolae Testemiţanu State University of Medicine and Pharmacy of the Republic of Moldova (1945-2020)