Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects
Küçük Resim Yok
Tarih
2014
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Arquivos Brasileiros Cardiologia
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Background: Pazopanib (PZP) may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT) in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6). The first group (normal group) received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient (R) tablet) perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP), to the normal group and to the second group (control-PZP+SP group); 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca), to the third group (PZP+metoprolol group); and 1 mg/kg diltiazem (Diltiazem, Mustafa Nevzat), to the fourth group (PZP+diltiazem group). One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 +/- 3.62 ms; control-PZP+SP group, 131.23 +/- 12.21 ms; PZP+metoprolol group, 89.36 +/- 3.61 ms; and PZP+diltiazem group, 88.86 +/- 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001). Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.
Açıklama
Anahtar Kelimeler
Arrhythmias, Cardiac / therapy, Pyrimidines / adverse effects, Heart Conduction System / physiology, Heart / physiology
Kaynak
Arquivos Brasileiros De Cardiologia
WoS Q Değeri
Q4
Scopus Q Değeri
Cilt
103
Sayı
5
