Reduction of adriamycin cardiotoxicity by enoximone.
Several non catecholamine, non glycoside cardiotonic drugs have been described recently. New compounds include amrinone, sulmazole, milrinone and pimobendan. In an attempt to alleviate or prevent anthracycline toxicity, we have reported that these compounds reduce the negative effects of adriamycin, 4-epiadriamycin and esorubicin in isolated guinea pig atria. The present study reports the effects of a new cardiotonic agent: enoximone. Enoximone was administered after adriamycin (100 micrograms/ml) on the isolated and spontaneously beating atria, and on electrically driven left atria of guinea pig-in normodynamic and hypodynamic conditions. Exposure for 60 minutes to the antitumor drug causes a depression of contractile force (g) and its derivative versus time (dF/dt, as maximal rate of contractile force). The negative effects of adriamycin are antagonised by enoximone (100, 200 micrograms/ml).
Bossa
R
R
Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica-E. Trabucchi-, Università di Milano, Italy.
Bissoli
M
M
Chiericozzi
M
M
Cozzi
R
R
Galatulas
I
I
Salvatore
G
G
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D016279:Atrial Function, Left / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004317:Doxorubicin / Q000633:toxicity*; D004347:Drug Interactions; D017335:Enoximone / Q000627:therapeutic use*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D004317:Doxorubicin; D017335:Enoximone