Recombinant lys-plasminogen, but not glu-plasminogen, improves recombinant tissue-type plasminogen activator-induced coronary thrombolysis in dogs

Objectives. This study examined the modification of recombinant tissue-type plasminogen activator (rt-PA)-induced thrombolysis by recombinant lys-plasminogen. Background. Recombinant tissue-type plasminogen activator restores flow in the thrombosed coronary artery, but the artery often reoccludes. The rt-PA-induced thrombolysis is result of activation of plasminogen bound to fibrin in the thrombus and results in generation of the fibrinolytic enzyme plasmin. Small amounts of lys-plasminogen are formed when rt-P is used. Lys-plasminogen binds to fibrin with 10-fold greater affinity than the predominant native glu-plasminogen, leading to loose fibrin structure. Methods. Dogs with electrically induced occlusive intracoronary thrombus were treated with saline solution (n = 9), gluplasminogen (2 mg/kg body weight, n = 5) or lys-plasminogen (2 mg/kg, n = 5), followed by infusion of rt-P (1 mg/kg over 20 min) 10 min later. Results. Reperfusion rates were similar in all groups of dogs, but the time to reflow was lowest in dogs given lys-plasminogen compared with those given saline solution or glu-plasminogen before rt-P (mean [±SE]14 ± 2 vs. 22 ± 2 and 23 ± 3 min, respectively, p < 0.05). None of the reperfused coronary arteries reoccluded in the lys-plasminogen plus rt-P group, whereas 75% reoccluded in dogs given saline solution plus rt-PA, and 50% reoccluded in those given glu-plasminogen plus rt-PA. Accordingly, duration of reflow was greater in the lys-plasminogen plus rt-P group (> 120 vs. 39 ± 7 and 82 ± 21 min, respectively, p < 0.05). Plasminogen activator inhibitor-1 activity decreased during rt-P infusion and thereafter increased in all dogs, but less so in dogs given lys-plasminogen (p < 0.05 vs. those given saline solution before rt-PA). Conclusions. Treatment with recombinant lys-plasminogen before rt-P reduces time to reflow and sustains reflow after thrombolysis, whereas glu-plasminogen has no such effect.