Evaluation of ECG time intervals in a rabbit model of anthracycline-induced cardiomyopathy: a useful tool for assessment of cardioprotective agents.
The aim of this study was to analyze the ECG time intervals in the course of the development of chronic anthracycline cardiomyopathy in rabbits. Furthermore, this approach was employed to study the effects of a model cardioprotective drug (dexrazoxane) and two novel iron chelating compounds--salicylaldehyde isonicotinoyl hydrazone (SIH) and pyridoxal 2-chlorobenzoyl hydrazone (o-108). Repeated daunorubicin administration induced a significant and progressive prolongation of the QRS complex commencing with the eighth week of administration. At the end of the study, we identified a significant correlation between QRS duration and the contractility index dP/dt(max) (r = -0.81; P<0.001) as well as with the plasma concentrations of cardiac troponin T (r = 0.78; P<0.001). In contrast, no alterations in ECG time intervals were revealed in the groups co-treated with either dexrazoxane or both novel cardioprotective drugs (SIH, o-108). Hence, in this study, the QRS duration is for the first time shown as a parameter suitable for the non-invasive evaluation of the anthracycline cardiotoxicity and cardioprotective effects of both well established and investigated drugs. Moreover, our results strongly suggest that novel iron chelators (SIH and o-108) merit further study as promising cardioprotective drugs against anthracycline cardiotoxicity.
Potáčová
A
A
Faculty of Medicine, Charles University, Hradec Králové, Czech Republic.
Adamcová
M
M
Čajnáková
H
H
Hrbatová
L
L
Sterba
M
M
Popelová
O
O
Šimůnek
T
T
Ponka
P
P
Gersl
V
V
D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D009202:Cardiomyopathies / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002908:Chronic Disease; D003630:Daunorubicin; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004562:Electrocardiography; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006835:Hydrazones / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011730:Pyridoxal / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D011929:Razoxane / Q000494:pharmacology; D013997:Time Factors; D020107:Troponin T / Q000097:blood
D000447:Aldehydes; D002316:Cardiotonic Agents; D006835:Hydrazones; D007502:Iron Chelating Agents; D020107:Troponin T; C507461:pyridoxal 2-chlorobenzoyl hydrazone; C413684:salicylaldehyde isonicotinoyl hydrazone; D011730:Pyridoxal; D011929:Razoxane; D003630:Daunorubicin