Doxorubicin-induced hypotension in the beagle dog

Abstract

Rapid intravenous administration of doxorubicin (0.18–3.0 mg/kg) lowered systemic arterial pressure in anesthesized beagle dogs. The threshold hypotensive dose was between 0.375 and 0.75 mg/kg; doses of 1.5–3.0 mg/kg produced up to 75% depression of arterial pressure for periods of 15 to >30 min. Respiratory difficulty was also present at these doses. When doxorubicin (1.5 mg/kg) was given repeatedly, the magnitude of the hypotensive response decreased with each succeeding dose. Pretreatment with either atropine (1.0 mg/kg) ordl-propranolol (0.5 mg/kg) did not alter the fall in arterial pressure due to doxorubicin administration. In contrast, the response was almost completely eliminated when compound 48/80 (1 mg/kg) was given 1 h prior to doxorubicin (1.5 mg/kg). Also, the intensity and duration of the hypotensive response was decreased by pretreatment with the H1 histamine blocker tripelennamine (6 mg/kg), while the response was almost completely eliminated in animals pretreated with a combination of tripelennamine (6 mg/kg) and the H2 histamine blocker cimetidine (15 mg/kg). Significant increases in plasma histamine were detected immediately after the injection of doxorubicin (1.5 mg/kg).