Abstract
Artificially ventilated anesthetized dogs were given imipramine 7.5 mg/kg/hr i.v. In the first group (n=6) mechanical cardiac activity was no longer detectable after a cumulative dose of 20.0 + 6.6 mg/kg (mean ± sd). When aortic flow had decreased to 75% of its initial value, in a second group (n=5) of experiments dopamine 10 μg/kg/min and in a third group (n=5) isoproterenol 1 μg/kg/min were administered i.v. The doses of dopamine and isoproterenol were doubled when aortic flow had again decreased to 75% and 100%, respectively, of the original values. Cardiac mechanical activity was not detectable after a cumulative dose of 43.8 ± 13.3 in the dopamine and 42.5 ± 8.0 mg imipramine/kg in the isoproterenol group. These values differed significantly from that in the reference group (both 0.01 > p > 0.001). In the first group plasma imipramine concentrations at the end of the experiments were 3.06 ± 0.66, in the second 3.36 ± 0.66 and in the third 3.32 ± 1.10 mg/1. Desipramine concentrations were 0.078 ± 0.06, 0.162 ± 0.076 and 0.383 ± 0.09 mg/1 respectively. Dopamine induced a hemodynamic profile of low output and high pressure and isoproterenol one of low pressure and high output. It is concluded that dopamine combined with isoproterenol might be effective in counteracting the cardiodepressant action of imipramine.