Enhancement ofthrombolysis withtissue-type plasminogen activator bypretreatment withheparin

Theeffect ofpretreatment withheparin on lysis ofarterial thrombi bytissue-type plasminogen activator (rt-PA) was studied in19dogs. Copper coil-induced carotid artery thrombi were weighed, inserted into thefemoral arteries, andexposed toa 15mininfusion ofrt-PA at10,ug/kg/min either with(n= 6thrombi) orwithout pretreatment with a 200unit/kg bolus ofheparin (n= 6 thrombi). Theinfusion ofrt-PA without pretreatment reduced thethrombus weight by27.6+ 7.4%, while infusion ofrt-PA withpretreatment reduced itby79.1+ 12.3%(p< .0001). Totestthe hypothesis that heparin enhanced thrombolysis bypreventing continued incorporation ofnew fibrin into thethrombus during thrombolysis we repeated theexperiments using pretreatment with8U/kgof ancrod, which rapidly depletes fibrinogen. Pretreatment withancrod (n= 6thrombi) depleted fibrino- genandenhanced thelytic effect ofrt-PA toasimilar degree aspretreatment withheparin, resulting ina 67.6+ 12.3%(NS)decrease inthrombus weight. Weconclude that heparin significantly enhances the thrombolytic effect ofrt-PA, probably bypreventing new fibrin formation andits incorporation into the thrombus during lysis. Circulation 74,No.3,583-587, 1986. ITHASBEENSHOWNthat thrombi continue togrow byincorporation ofnewfibrin forupto72hr,andthat this growth isparticularly fast during thefirst few hours.2 Thrombus growth that continues during lysis3'4 increases thetotal amountofthrombus tobelyzed during thrombolytic treatment andthereby probably delays recanalization oftheinfarct-related artery and reduces thepotential formyocardial salvage inpatients withacute myocardial infarction. Heparin hasbeen showntoprevent newfibrin formation anditsincor- poration into thethrombus.S Accordingly, thepurpose ofthis study wastoinves- tigate whether lysis ofarterial thrombi after adminis- tration oftissue-type plasminogen activator (rt-PA) could beenhanced bypretreatment withheparin.