Augmentation of Streptokinase-Induced Thrombolysis by Heparin and Prostacyclin

Abstract

The ability of heparin and prostacyclin to improve streptokinase-induced recanalization was examined in open-chest dogs subjected to thrombotic occluson of the left circumflex coronary artery. Vessel injury was produced by electrical stimulation of the intimal surface at the site of a noncircumferential fixed stenosis. Animals were divided into 3 treatment groups as follows: group 1 received intracoronary streptokinase alone (75,000 U/80 min starting 30 min postocclusion; n = 8); group 2 received streptokinase plus heparin (300 U/kg i.v. at 20 min postocclusion; n = 7); group 3 received streptokinase plus heparin prostacyclin (500 ng/kg per min, intracoronary, given intermittently during reperfusion; n = 7). The groups did not differ with respect to preocclusion coronary blood flow (27 .+-. 1 ml/min; .+-. SEM [standard error of the mean]), the duration of streptokinase infusion required to achieve reflow (15 .+-. 2 min), and the percentage of animals recanalized (85%). They did differ in the average rate of reflow, which was greater in group 2 (16 .+-. 2 ml/min) and group 3 (20 .+-. 4 ml/min) as compared with group 1 (6 .+-. 1 ml/min P < 0.05). The intermittent reocclusions which persisted during reperfusion in group 1 and 2 dogs were diminished during the periodic infusions of prostacyclin. Thrombus mass at the site of injury was comparable among groups. In contrast, distal circumflex thrombi, about twice the weight of the proximal mass, were observed in all groups 1 dogs and were undetectable in group 2 and 3 animals. Transient improvements in contractile force during reperfusion were observed only with groups 2 and 3. Heparin and prostacyclin are effective in increasing antegrade flow during recanalization achieved with thrombolytic therapy.