Aims: 

The increase of QT duration caused by drugs can induce life-threatening arrhythmias as Torsades de pointes (TdP). We studied the influence of claritromycin in combination with furosemide on ECG parameters in rats and their effect on occurence of TdP. We hypothetised, that gene rERG which encodes the expression of potassium channels and influences repolarization could be responsible for changes in QT interval and incidence of arrhythmias.

Methods: 

Wistar rats were treated 7 days with claritromycin (CLA, 100mg/kg, p.o., every 12 hrs), furosemide (FUR, 100mg/kg, p.o., every 12 hrs) or both (CLA+FUR). Controls (CON) received vehiculum. 12-lead ECG was recorded in rats under Avertin anaesthesia (10 ml/kg, i.p.). We evaluated the duration of QT and RR. ECG was monitored also during beta-adrenergic stimulation (isoproterenol i.v., dose 5, 10, 15, 20, 30, 45 a 60 ng/min). Using RT-PCR, we observed the expression of gene rERG in left ventricular tissue.

Results: 

The duration of QT was increased in groups in the order CON<FUR<CLA<CLA+FUR (83 ± 2 ms, 103 ± 4 ms, 111 ± 4 ms, 127 ± 5 ms, p < 0.05). The duration of RR was increased in groups, where furosemide was administered. In CLA+FUR group during beta-adrenergic stimulation, the occurrence of TdP was noted. In this group, there was also 30% decrease in expression of rERG compared to controls (p < 0.05). In other experimental groups, the expression of rERG did not change.

Conclusion: 

The chronic administration of claritromycin and furosemide increases the duration of QT and can induce TdP. We suppose this is associated with decreased expression of rERG.