Electrocardiographic effects
In rats, increases in the PR intervals occurred with all doses of chloroquine, and in proportion to the cumulative dose received. For example, the PR interval increased from 52 ± 3 to 68 ± 4 ms during the first 12 minutes in ventilated rats receiving 1 mg kg-1 min-1 chloroquine, and from 50 ± 2 to 68 ± 4 ms during the first 6 minutes at twice the infusion rate, with both groups receiving a total of 12 mg kg-1 of chloroquine over these periods. Chloroquine also caused a dose-dependent increase in the PR interval in rabbits.
Chloroquine broadened the QRS complex in all animals (Figure 2), although this was not as pronounced with the slower infusion rates as the changes in PR duration. In ventilated rats, for example, the QRS duration increased by 17% in the first 30 minutes of chloroquine being infused at 1 mg kg-1 min-1 while a 30% increase in PR interval occurred over the same period.
QT interval prolongations were observed with high infusion rates, but these were not as apparent when the QT was corrected for rate effects. A substantial increase in QTc occurred only with 2 mg kg-1 min-1 in ventilated rats.
Chloroquine induced arrhythmias in 34/38 rats. Typically, impairment of atrioventricular (AV) conduction leading to varying degrees of AV block, was associated with ventricular ectopy. Ventricular bigeminy sometimes preceded episodes of ventricular tachycardia in the latter stages of infusion. Ventricular tachycardia was commonly triggered by ‘R on T’ depolarizations. In three rats, the ventricular tachycardia was polymorphic with characteristic features of torsade de pointes. Two rats in each of the ventilated and non-ventilated groups did not experience cardiac arrhythmias at the lower dose of 0.5 mg kg-1min-1.
In all 16 rabbits, arrhythmias presented as Mobitz type II, second degree AV block with a conduction ratio of 2:1 (two P waves for each QRS complex). The onset of arrhythmias was dose dependent, and with higher degrees of block eventually occurring at the faster infusion rates. These largely degenerated to ventricular tachycardia and fibrillation.