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Updated: Aug 17, 2026
Transthoracic Echocardiographic Examination in the Rabbit Model
Published on: June 1, 2019
Myocardial content of selected elements in experimental anthracycline-induced cardiomyopathy in rabbits
Tomás Simůnek1, Martin Sterba, Magdaléna Holecková
1Charles University in Prague, Faculty of Pharmacy, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. simunekt@faf.cuni.cz
Abstract:
Cardiotoxicity represents the main drawback of clinical usefulness of anthracycline antineoplastic drugs. In this study, a content of selected elements (Ca, Mg, K, Se, Fe) in the post-mortem removed samples of the myocardial tissue was studied in three groups of rabbits: 1) control group (i.v. saline; n = 10); 2) daunorubicin-receiving animals (DAU; 3 mg/kg, i.v; n = 11); 3) animals receiving cardioprotective iron-chelating agent dexrazoxane (DEX; 60 mg/kg, i.p.; n = 5) prior to DAU. Drugs were administered once weekly for 10 weeks. 5-7 days after the last administration, cardiac left ventricular contractility (dP/dtmax) was significantly decreased in DAU-treated animals (745 +/- 69 versus 1245 +/- 86 kPa/s in the control group; P < 0.05), while in the DEX + DAU group it was insignificantly increased (1411 +/- 77 kPa/s). Of the myocardial elements' content studied, a significant increase in total Ca against control (16.2 +/- 2.4 versus 10.6 +/- 0.9 microg/g of dry tissue; P < 0.05) was determined in the DAU-group, which was accompanied with significant decreases in Mg and K. In the heart tissue of DEX-pretreated animals, no significant changes of elements' content were found as compared to controls, while the Ca content was in these animals significantly lower than in the DAU group (9.1 +/- 0.4 versus 16.2 +/- 2.4 microg/g; P < 0.05). Hence, in this study we show that systolic heart failure induced by chronic DAU administration is primarily accompanied by persistent calcium overload of cardiac tissue and the protective action of DEX is associated with the restoration of normal myocardial Ca content.
Insights
Anthracycline chemotherapy causes heart failure by increasing myocardial calcium. The cardioprotective agent dexrazoxane prevents this calcium overload and preserves heart function in rabbits.
Area of Science:
- Cardiology
- Oncology
- Toxicology
Background:
- Anthracycline antineoplastic drugs are effective cancer treatments but cause cardiotoxicity, limiting their clinical use.
- Myocardial damage from anthracyclines is a significant clinical concern.
- Understanding the mechanisms of anthracycline-induced cardiotoxicity is crucial for developing effective cardioprotective strategies.
Purpose of the Study:
- To investigate the role of myocardial elemental content in anthracycline-induced cardiotoxicity.
- To evaluate the cardioprotective effect of dexrazoxane against daunorubicin-induced cardiotoxicity.
- To determine if dexrazoxane's cardioprotective action is associated with altered myocardial elemental composition.
Main Methods:
- Three groups of rabbits were studied: control, daunorubicin-treated (DAU), and dexrazoxane + daunorubicin-treated (DEX + DAU).
- Drugs were administered weekly for 10 weeks.
- Post-mortem myocardial tissue samples were analyzed for calcium (Ca), magnesium (Mg), potassium (K), selenium (Se), and iron (Fe) content. Left ventricular contractility (dP/dtmax) was measured.
Main Results:
- Daunorubicin treatment significantly decreased left ventricular contractility and increased myocardial calcium content, while decreasing magnesium and potassium.
- Dexrazoxane pretreatment prevented the decrease in contractility and the increase in myocardial calcium induced by daunorubicin.
- In DEX + DAU animals, myocardial calcium levels were significantly lower than in DAU-only animals and comparable to controls.
Conclusions:
- Chronic daunorubicin administration induces systolic heart failure associated with persistent calcium overload in cardiac tissue.
- The cardioprotective effect of dexrazoxane is linked to the normalization of myocardial calcium content.
- These findings highlight the critical role of calcium dysregulation in anthracycline cardiotoxicity and dexrazoxane's efficacy in mitigating this effect.
