Dobutamine enhances recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism

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We used a canine model of pulmonary embolism, induced by injection of radioactive autologous blood clots, to test the hypothesis that a dobutamine-mediated increase in cardiac output (CO) would enhance recombinant tissue plasminogen activator (rtPA)-induced pulmonary thrombolysis. Emboli increased mean pulmonary artery pressure from 15 to 36 mm Hg ( P < .001). There was a corresponding fall in mean CO, from 2.3 to 1.7 L/min ( P < .001). Following embolization, dogs were randomly divided into three groups: group 1 dogs received rtPA, 0.5 mg/kg over 30 minutes; group 2 dogs received dobutamine prior to the same dose regimen of rtPA to increase mean CO from 1.8 to 3.4 L/min; and in group 3 dogs, prior to receiving rtPA, mean CO was increased from 1.7 to 3.2 L/min by opening a systemic arteriovenous fistula. Corresponding to the increase in CO in groups 2 and 3, the rate and extent of pulmonary thrombolysis increased. During drug infusion, the rate of pulmonary thrombolysis was 10.6% for 30 minutes in group 1 and significantly increased to 18.1 % and 21.0% for 30 minutes in groups 2 and 3, respectively. In addition, the extent of total pulmonary thrombolysis was significantly increased in groups 2 and 3 compared with group 1. While the rate of thrombolysis was similar in groups 2 and 3 during drug infusion, the extent of total thrombolysis was greater with the latter regimen. These results indicate that the combination of dobutamine and rtPA may be appropriate therapy when a low CO complicates pulmonary embolism.