Blockade of tissue uptake of the antineoplastic agent, doxorubicin.
Myocardial uptake of doxorubicin (Adriamycin) and its inhibition by digoxin and propranolol were studied in paced, isolated perfused cat hearts using tritiated doxorubicin. Contractility was studied using a Walton-Brody strain gauge arch and its first derivative. Coronary blood flow was measured by collecting the effluent from the heart. The myocardial content of doxorubicin was 0.069 +/- 0.101 nmol/mg after 30 minutes. Combined administration of doxorubicin and digoxin reduced the myocardial content of doxorubicin to 0.025 +/- 0.010 nmol/mg (P less than .02). The combination increased contractility compared with doxorubicin alone and increased coronary blood flow compared with digoxin alone. The reduction in the myocardial content of digoxin by doxorubicin was not significant. Propranolol also reduced the myocardial uptake of doxorubicin (P less than .05) without changing coronary blood flow and without further reducing contractility. Thus, both propranolol and digoxin merit evaluation in preventing doxorubicin cardiotoxicity.
D000818:Animals; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects; D003864:Depression, Chemical; D004077:Digoxin / Q000494:pharmacology*; D004317:Doxorubicin / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology*
D004077:Digoxin; D004317:Doxorubicin; D011433:Propranolol