Dexrazoxane protects the heart from acute doxorubicin-induced QT prolongation: a key role for I(Ks).

Joffrey Ducroq (1) , H. Moha Ou Maati (1, 2) , S. Guilbot (1) , S. Dilly (3) , E. Laemmel (4) , C. Pons-Himbert (5) , J. F. Faivre (2) , P. Bois (2) , O. Stücker (5) , M. Le Grand (1)

1 PHYSIOSTIM
2 IPBC - Institut de physiologie et biologie cellulaires
3 APT Pharmaceuticals
4 LEM - Laboratoire d'Étude de la Microcirculation
5 CEROM

Doxorubicin acutely prolonged the QT interval in guinea-pig heart by selective I(Ks) blockade. This effect was prevented by dexrazoxane. This result is important because it illustrates the danger of neglecting I(Ks) in favour of hERG screening alone, for early preclinical testing for possible induction of torsade de pointes.

Domaines: Biophysique; Cardiologie et système cardiovasculaire; Médicaments; Pharmacologie

Joffrey Ducroq, H. Moha Ou Maati, S. Guilbot, S. Dilly, E. Laemmel, et al.. Dexrazoxane protects the heart from acute doxorubicin-induced QT prolongation: a key role for I(Ks).. British Journal of Pharmacology, 2010, 159 (1), pp.93-101. ⟨10.1111/j.1476-5381.2009.00371.x⟩. ⟨hal-00561579⟩