Haemodynamic effects
In both rats and rabbits, marked, dose-dependent decreases in systolic and diastolic blood pressures were observed during continuous infusions of chloroquine (Figure 1). In spontaneously breathing rats, the highest dose of chloroquine (4 mg kg-1min-1) caused the most pronounced effect, with a reduction in systolic pressure from 123 ± 15 to 37 ± 6 mmHg occurring during the first 8 minutes. Similar reductions in pressure were observed in ventilated rats receiving chloroquine although baseline values were lower, as expected in thoracotomised rats. Equivalent depressor responses in rabbits occurred with approximately twofold less chloroquine.
Chloroquine caused dose-dependent negative inotropy in both species. Reductions in LV +dP/dtmax during the first 2 to 4 minutes of infusion seemed more pronounced than reductions in blood pressure. For example, a 47% reduction in LV +dP/dtmaxoccurred during the first 2 minutes of infusion at 2 mg kg-1 min-1 compared with a 15% reduction in diastolic pressure for the same period in non-ventilated rats. Cardiac lusitropy (LV -dP/dtmax) declined in a parallel manner to the negative inotropic response. Increases in left ventricular end diastolic pressure were observed with chloroquine in non-ventilated rats and ventilated rabbits.
Chloroquine caused a similar dose-dependent bradycardia over the time course of the experiment in both ventilated and non-ventilated rats for the corresponding doses. In rabbits, however, heart rate declined abruptly by approximately half at time points corresponding to the onset of arrhythmias.