Diastolic disorder inherent to doxorubicin cardiotoxicity

Abstract

Background: The doxorubicin (Dx) cardiotoxicity is manifested by a marked heart failure evolution. The impact of Dx on lusitrop functions of the heart and the inherent diastolic disorders have a theoretical and practical value for the connection cardiology-oncology. Material and methods: Dx cardiotoxicity was reproduced by its administration i/p in white rats in cumulative dose 16 mg/kg (Dx group n=9). Control group (n=9) received only physiological solution. The study was performed in vitro by using models of isolated heart perfusion in either isovolumic or exterior working regimens. The assayed indices of diastole functioning were: left ventricle (LV) end-diastolic pressure (LVEDP), diastolic stiffness, isovolumic relaxation velocity (-dP/dTmax) and protodiastolic pressure of LV (LVPDP). Results: The indices of diastolic disorders induced by Dx were elevation of LVEDP, diastolic stiffness and LVPDP in a range of 97-168% comparing to control as well as diminution of -dP/dTmax in the physiological pattern of hemodynamics. LVEDP increased more in conditions of calcium overloading or endothelin-1 (ET-1) action that are involved in pathogenesis of diastolic rigidity. Dx action led to decrease of myocardium resistance to ischemiareperfusion action resulting in the LVEDP elevation by 53% comparing to control. Conclusions: 1. Diastolic disorders inherent to Dx cardiotoxicity are manifested by the increase of LVEDP and diastolic stiffness. 2. Diastolic disorders compromised the volume-pressure relationship of LV, the adaptation of the heart to effort with volume, being more pronounced during the action of calcium excess and ET-1.