Enhancement of coronary thrombolysis with plasminogen pro-activator by pretreatment with heparin

The effect of pretreatment with heparin on coronary thrombolysis by plasminogen pro-activator was studied in 20 dogs with a 1-h old clot in the left anterior descending coronary artery. The clot was induced by placement of a copper coil and thrombolysis was confirmed angiographically. Intravenous administration of plasminogen pro-activator at a rate of 5 micrograms/kg/min (group 1; n = 5) and 20 micrograms/kg/min (group 2; n = 5) after pretreatment with heparin (300 IU/kg) induced thrombolysis in 31 +/- 4 min and 14 +/- 2 min, respectively. When plasminogen pro-activator was administrated intravenously at a rate of 20 micrograms/kg/min without heparin pretreatment (group 3; n = 5), the infusion interval for successful thrombolysis was prolonged to 45 +/- 6 min, which was significantly longer than that in groups 1 and 2 (p less than 0.001). In these three treatment groups, thrombolysis was not associated with severe alteration in plasma hemostatic factors (fibrinogen and alpha 2-antiplasmin). An evaluation of plasma urokinase activities using a chromogenic substrate S-2444 did not show that heparin increased the plasma urokinase activities. By increasing the dose of plasminogen pro-activities. By increasing the dose of plasminogen pro-activator to 80 micrograms/kg/min, successful reperfusion was rapidly obtained in 25 +/- 5 min without heparin pretreatment (group 4; n = 5); this was significantly faster than the results seen in group 3 (p less than 0.001). An analysis of urokinase activities showed that plasminogen pro-activator was fully converted to urokinase, which induced complete depletion of fibrinogen and alpha 2-antiplasmin.(ABSTRACT TRUNCATED AT 250 WORDS)