Effects of flow on recombinant tissue plasminogen activator-induced pulmonary thrombolysis

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We employed a canine model of pulmonary embolism induced by injection of radioactive blood clots to investigate effects of changes in cardiac output (CO) on recombinant tissue plasminogen activator- (rtPA) induced pulmonary thrombolysis. Rate and extent of thrombolysis were assessed with a gamma camera. Eighteen dogs were studied. Emboli increased mean pulmonary arterial pressure and decreased CO from 2.6 to 1.9 l/min (P less than 0.001). Subsequently, dogs were randomly divided into three groups: group 1 received 0.5 mg/kg of rtPA over 30 min; 30 min before the same dose regimen of rtPA, in the six group 2 dogs, mean CO was increased to approximately 3.25 l/min by opening one systemic arteriovenous fistula; in the six group 3 dogs, before rtPA, mean CO was increased to approximately 4.5 l/min by opening two or three fistulas. After embolization, CO remained low in group 1; the mean 2-h time-averaged CO was 1.8 l/min. CO was much higher in groups 2 and 3 (3.3 and 4.6 l/min, respectively; both P less than 0.001 compared with group 1; and P less than 0.001, group 2 vs. group 3). Compared with group 1, corresponding to the increased flow in groups 2 and 3, rate and extent of pulmonary thrombolysis significantly increased. These results indicate that an increase in flow per se augments rtPA-induced pulmonary thrombolysis. Also, because thrombolysis was similar between groups 2 and 3, these results define an upper limit to the flow-thrombolytic relationship with rtPA.