Effects of intravenous versus intraatrial administration of doxorubicin on the function and structure of the heart

To evaluate the relationship of toxicity of doxorubicin to route of administration, we studied 21 mongrel dogs which were randomly assigned to one of three groups: 1) a control group undergoing intraatrial indwelling catheter placement but no drug therapy; 2) an IV group receiving weekly doxorubicin by peripheral IV bolus administration; and 3) a catheter group receiving weekly doxorubicin through an indwelling intraatrial catheter. After 8 weeks all dogs were evaluated hemodynamically and then sacrificed. Sections of right ventricle were evaluated by light and electron microscopy. Although no hemodynamic alterations were found in any of the three groups, significant ultrastructural damage consistent with doxorubicin cardiac toxicity was demonstrable in four of the six evaluable catheter dogs receiving intraatrial doxorubicin, but in none of the other 13 dogs evaluated. This finding suggests that the intraatrial administration of doxorubicin may lead to cardiac toxicity at a lower cumulative dose than noted with peripheral IV administration.