Positive effects of dexrazoxane (DEX) in anthracycline cardiotoxicity have been mostly assumed to be associated with its iron-chelating properties. However, this explanation has been recently questioned. Iron plays also an important role in the catecholamine cardiotoxicity. Hence in this study, the influence of DEX on a catecholamine model of acute myocardial infarction (100 mg/kg of isoprenaline by subcutaneous injection) was assessed: (i) the effects of an intravenous dose of 20.4 mg/kg were analyzed after 24 h, (ii) the effects were monitored continuously during the first two hours after drug(s) administration to examine the mechanism(s) of cardioprotection. Additional in vitro experiments on iron chelation/reduction and influence on the Fenton chemistry were performed both with isoprenaline/DEX separately and in their combination. DEX partly decreased the mortality, reduced myocardial calcium overload, histological impairment, and peripheral haemodynamic disturbances 24 h after isoprenaline administration. Continuous 2 h experiments showed that DEX did not influence isoprenaline induced atrioventricular blocks and had little effect on the measured haemodynamic parameters. Its protective effects are probably mediated by inhibition of late myocardial impairment and ventricular fibrillation likely due to inhibition of myocardial calcium overload. Complementary in vitro experiments suggested that iron chelation properties of DEX apparently did not play the major role.
- MeSH
- chelátory železa farmakologie MeSH
- hemodynamika účinky léků MeSH
- infarkt myokardu chemicky indukované farmakoterapie MeSH
- isoprenalin antagonisté a inhibitory MeSH
- kardiotonika farmakologie terapeutické užití MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- myokard metabolismus patologie MeSH
- potkani Wistar MeSH
- razoxan farmakologie terapeutické užití MeSH
- vápník metabolismus MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- experimenty na zvířatech MeSH
- financování organizované MeSH
- flavonoidy aplikace a dávkování farmakologie MeSH
- isoprenalin diagnostické užití toxicita MeSH
- kardiotoxiny diagnostické užití toxicita MeSH
- kardiovaskulární nemoci etiologie farmakoterapie MeSH
- katecholaminy diagnostické užití toxicita MeSH
- potkani Wistar MeSH
- reaktivní formy kyslíku farmakologie MeSH
- rutin diagnostické užití MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- abstrakty MeSH
