Abstract

The aim of the study was comparison of contractile function of isolated hearts of rats with doxorubicin-induced myocardial injury which were tentatively divided according to the level of ejection fraction determined by echocardiography in vivo. After 4 weeks of doxorubicin administration (2 mg/kg subcutaneously once a week) about half of animals had normal (86±1%) and the other half reduced (61±4%) ejection fraction. The first group was defined as diastolic heart failure (DHF) and the other as systolic (SHF). The maximal pressure developed by the isolated heart in isovolumic mode was reduced in DHF by 13%, and in SHF by 34%. The relaxation index in both groups was lowed by 22-24%. Both groups were characterized by a decline in the ability to raise developed pressure while increasing coronary perfusion pressure, as well as by the loss of the ability of coronary vessels to maintain a stable flow rate while increasing perfusion pressure. The hearts of control animals were able to raise the cardiac work index (the product of developed pressure and heart rate) during prolonged high frequency (7-9 Hz) stimulation, while the two groups treated with doxorubicin reduced the level of this index. The content of basic energy metabolites (ATP, phosphocreatine, creatine) in both groups was reduced by 20-38%. The results showed that the hearts in DHF and SHF groups showed approximately the same level of reduction of the contractile function and energy metabolism, and hence their difference in vivo was probably due to varying degrees of mobilization of compensatory mechanisms.

Highlights

  • The results showed that the hearts in diastolic heart failure (DHF) and SHF groups showed approximately the same level of reduction of the contractile function and energy metabolism, and hence their difference in vivo was probably due to varying degrees of mobilization of compensatory mechanisms

  • Анализ изменений энергетических метаболитов позволяет предполагать, что снижение уровня АТФ в кардиомиоцитах обусловлено лишь частично снижением синтеза АТФ в митохондриях, поскольку содержание лактата в сердце животных, получавших доксорубицин, оставалось практически неизменным, а скорее повреждением мембран и, прежде всего, мембранного белка – переносчика креатина

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Summary

Introduction

Видно, что сердца крыс, получавших доксорубицин в течение 4 нед, отличались меньшей крутизной подъема развиваемого давления, и из‐за исходно повышенной скорости потока это соотношение сдвинуто вправо. В отличие от этого, сердца крыс, получавших доксорубицин в течение 4 нед, увеличивали скорость потока пропорционально возрастанию давления, что свидетельствует об утрате этой компенсаторной реакции.

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