Relationship between doxorubicin-induced ECG changes and myocardial alterations in rats.

The aim of the present study was to evaluate the dose- and time-dependence of the effect displayed by doxorubicin (DXR) on the electrocardiogram (ECG) and to establish the relationship between structural alterations of the myocardium and ECG changes in rats administered DXR, at a dose of 1.5 or 3.0 mg/kg, every 3 days for a total of three administrations. The most interesting findings consisted of a dose-dependent, but reversible prolongation of the QRS complex, and in a dose-dependent and progressive irreversible increase in QaT and, in particular, in SaT duration. Furthermore, animals treated with the higher DXR dose showed a slight increase in serum K+ concentration and a significant decrease in serum Ca2+ levels. A good correlation was found between the morphologic score indicating the degree of observed tissue damage and SaT prolongation. These results therefore support the usefulness of measuring this ECG parameter for monitoring the development of DXR-induced cardiotoxicity in rats

Trifluoperazine does not affect doxorubicin cardiotoxicity in the rat.

Sprague Dawley rats received doxorubicin (DXR) at a dose of 3 mg/kg i.v. every third day for a total of three administrations, according to an acute and delayed cardiotoxicity experimental model previously described. DXR was found to induce significant ECG alterations (Qat and Sat prolongation) and typical morphologic lesions in the left ventricle. Trifluoperazine (TFP), administered at the doses of 0.2 of 2 mg/kg i.p., 5 days a week for 4 weeks, starting 1 day before DXR, was ineffective in preventing the electrocardiographic and morphologic alterations induced by DXR

Effect of ICRF-187 pretreatment against doxorubicin-induced delayed cardiotoxicity in the rat

Doxorubicin (DXR), administered iv in rats at the weekly dose of 3 mg/kg for 5 weeks, significantly impaired body weight gain and induced irreversible ECG alterations, mainly consisting of a progressive prolongation of ST and QT intervals. Five weeks after the last DXR administration, the contractile performance of atria isolated from treated animals was significantly reduced. At the same time, relevant morphologic lesions, consisting of myocyte vacuolization and myofibrillar loss, were also present in the myocardium of the same rats. The study showed that ICRF-187, administered ip at a dose of 125 mg/kg, significantly prevented body weight loss. QT and ST prolongation, and the decreased contractile force induced by DXR. In addition, ICRF-187 caused a significant reduction in incidence and severity of myocardial lesions. The cardioprotective effect of ICRF-187 is not mediated by a modification in DXR pharmacokinetics in heart, since the drug was actually found to increase DXR uptake in myocardial cell