Adriamycin (ADR) is a widely used drug for the treatments of
cancers. This study evaluates the effects of
moxonidine and
metoprolol on cardiac hemodynamics and survival in ADR-induced
left ventricular dysfunction (total dose of 20 mg/kg in a 4-week regimen). Rats were treated with the centrally acting I(1)R agonist sympatho-inhibitor,
moxonidine, or with the non-selective
beta-adrenergic antagonist,
metoprolol, during 1 month or until death. Treatments began 1 week after the onset of the ADR administration. Low doses (0.5 and 1 mg/kg/day) of
moxonidine and
metoprolol (10 mg/kg/day) improved cardiovascular function. High doses of
moxonidine (3 mg/kg/day) and
metoprolol (150 mg/kg/day) were cardiodepressive.
Moxonidine and
metoprolol both failed to improve survival. These data indicate that a treatment with these sympatho-inhibitors can reduce the
left ventricular dysfunction induced by ADR. Moreover, these cardioprotective effects where obtained even when ADR was used at a dose regimen usually employed for its
antineoplastic effects in rodents. Nevertheless, in this particular
cardiomyopathy, we did not find any association between improvements of functional parameters and survival whatever the drug and the dose used. This problem points out the difficulty to prevent, at least with sympatho-inhibitory drugs alone, the mortality linked to the chronic
cardiotoxicity of ADR.