In vitro cardiac tissues
Tissues from 57 rats (272 ± 4 g) were used. Decreases in the developed tension of left atria were observed with chloroquine at the highest concentration of 100 µM. The negative inotropic effect was time-dependent, with maximal changes observed by 30 minutes. Chloroquine did not significantly alter the developed tension or time to peak tension of right ventricular strips or papillary muscles; but increased the time to peak tension in atria (70 ± 4 ms with chloroquine (100 µM) compared to 54 ± 2 ms in the control group; p<0.05). Chloroquine prolonged the ERP of all tissues. In left atria, for instance, the pre-chloroquine ERP was 41 ± 2 ms (in the 30 μM group), which increased to 72 ± 9 ms after 30 minutes exposure to chloroquine (p<0.001).
Diazepam alone was without effect on papillary muscles or ventricular tissue other than a small but significant increase from 65 ± 2 to 74 ± 2 ms in the time to peak tension of contracting right ventricular strips at 100 μM. However, diazepam 100 μM evoked a positive inotropic response and prolonged the ERP of left atria, and had a negative chronotropic effect on right atria (213 ± 11 versus 290 ± 14 beats min-1; p<0.001).
Diazepam in the concentration range of 1 to 100 μM did not appear to protect against the effects of 30 μM chloroquine (Table 2). At the highest concentration, diazepam lengthened the ERP and extended the time to peak tension in left atria, and reduced rate of beating right atria.