Key result
Doxorubicin induces systolic dysfunction in ~67% of rats, marked by reduced LVEF.
Why the study?
The study aimed to conduct a detailed investigation of pressure-volume loop curves in the rat heart during the development of doxorubicin cardiomyopathy.
Does doxorubicin administration alter left ventricular pressure and volume characteristics in a rat model of cardiomyopathy?
Does doxorubicin administration alter left ventricular pressure and volume characteristics in a rat model of cardiomyopathy?
Answers are grounded in this paper and cite their sources.
Doxorubicin-induced cardiomyopathy is characterized by specific compensatory mechanisms including slowing of myocardial relaxation, reduced peripheral arterial resistance, and heart rate reduction.
The Aim of the study was a detailed investigation of pressure volume-loop (PV-loop) curves in the rat heart during development of doxorubicin cardiomyopathy. Materials and methods . Cardiomyopathy in rats has been developed after 4 weeks doxorubicin administration (2 mg / kg weekly). Results . Echocardiographic study of rats in 8 weeks from onset of doxorubicin administration showed preponderance of systolic dysfunction (67 %) with decrease of left ventricular (LV) ejection fraction (EF) by 30 %. Simultaneous registration of LV pressure and volume showed that diastolic LV volume was preserved in doxorubicin-treated rats due to considerable lengthening of the diastole, the heart rate was reduced by 22 %. These hearts also showed slowing of relaxation, reduced maximal rate of pressure development and stroke work, as well as significant reduction in peripheral arterial resistance. Diastolic dysfunction differed from the systolic one by normal systolic EF and preserved LV contractility index as well as lower diastolic LV pressure throughout the diastole. Conclusions . Based on these data, four compensatory mechanisms associated with cardiomyopathy were distinguished - 1) slowing of myocardial relaxation, prolonging myofibrillar active state, 2) reduction of peripheral arterial resistance for easier LV ejection, 3) heart rate reduction, prolonging diastolic pause and thus facilitating better LV filling and 4) increased pressure in the small circle, also contributing to the LV rapid filling.
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Абрамов et al. (2019) studied Doxorubicin cardiomyopathy (n=30). Doxorubicin vs. Isotonic sodium chloride solution was evaluated on Systolic dysfunction (defined by decrease in left ventricular ejection fraction). Doxorubicin administration for 4 weeks induced systolic dysfunction in 67% of treated rats by 8 weeks, characterized by a 30% decrease in left ventricular ejection fraction.
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