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.