1988 Volume 52 Issue 1 Pages 72-78
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 μg/kg/min (group 1; n = 5) and 20 μg/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 μg/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 < 0.001). In these three treatment groups, thrombolysis was not associated with severe alteration in plasma hemostatic factors (fibrinogen and alpha2-antiplasmin). An evaluation of plasma urokinase activities using a chromogenic substrate S-2444 did not showed 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 g/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 <0.001). An analysis of urokinase activities showed that plasminogen pro-activator was fully converted to urokinase, which induced complete depletion of fibrinogen and alpha2-antiplasmin. These results suggest that heparin can enhance coronary thrombolysis in dogs and the mechanism of the enhancement is not related to the plasma urokinase activities. In addition, heparin may reduce the risk of the depletion of plasma fibrinogen by lowering the doses of plasminogen pro-activator necessary for reperfusion.
