ACUTE AND SUBACUTE EFFECTS OF DOXORUBICIN ON POSTEXTRASYSTOLIC POTENTIATION IN GUINEA-PIG PAPILLARY-MUSCLES

To investigate the effects of doxorubicin on postextrasystolic potentiation (PESP), isolated guinea pig papillary muscles were field-stimulated and the resulting isometric force was recorded. Postextrasystolic contraction was evoked following trains of 37 regular stimulations. The effects of acute doses of doxorubicin (0.2 mM) on regular contractions and postextrasystolic contractions were examined for 2 hr. The effects of subacute doses of doxorubicin (total dose 5 mg/kg intraperitoneally) on the relationship between %PESP (postextrasystolic/regular contraction) and both the extra-stimulus coupling interval and the postextrasystolic interval were examined. Acute administration of doxorubicin decreased the amplitude of postextrasystolic contractions more than that of regular contractions. Thus, %PESP in the doxorubicin-treated group decreased significantly over time. There was no similar decrease in the control papillary muscles. Both the extra-stimulus coupling interval and the postextrasystolic interval had less of an effect on %PESP in doxorubicin-treated animals than in control animals. Since PESP depends upon sarcoplasmic reticulum activity, our results indicate that acute and subacute exposure to doxorubicin impairs the activity of the sarcoplasmic reticulum of guinea pig papillary muscles.