The beneficial effect of lys-plasminogen upon the thrombolytic efficacy of urokinase in a dog model of peripheral arterial thrombosis.
The efficacy of thrombolytic therapy may be limited by local availability of plasminogen near a poorly perfused thrombus. The purpose of this study was to determine if the local (i.e., clot site) administration of 0.5 mg glu-plasminogen (glu-plg) or 0.5 mg lysplasminogen (lys-plg) could safely increase the thrombolytic efficacy of a 30-min intraarterial injection of 3,500 U kg-1 of two-chain urokinase plasminogen activator (UK) in a dog model of arterial thrombosis. Thrombolysis was measured by monitoring the continuous decrement of 125I-gamma emissions from a radiolabeled thrombus. Reflow was evaluated by a distally placed flowmeter and by direct visual examination. Forty-two dogs (mean weight 10.1 +/- 1.9 kg) were randomly sorted into six groups of 7 each. The dogs in each group were given either saline plus saline (group 1), saline plus UK (group 2), glu-plg plus saline (group 3), glu-plg plus UK (group 4), lys-plg plus saline (group 5), or lys-plg plus UK (group 6) by selective arterial catheterization 60 min after formation of an occlusive thrombus. Ninety minutes following drug administration, all groups which received UK (groups 2, 4, and 6) showed greater lysis (p less than 0.05) than the groups which received only saline or either glu- or lys-plg plus saline. Group 6, which received lys-plg plus UK, showed significantly greater lysis (34 +/- 4%) than both group 2 (23 +/- 2%), which received saline plus UK, and group 4 (19 +/- 3%), which received glu-plg plus UK (p less than 0.05). All dogs (7/7) in group 6 had reflow at 90 min whereas only 3/7 dogs had reflow in both groups 2 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)
Badylak
S F
SF
Hillenbrand Biomedical Engineering Center, Purdue University, W. Lafayette, Ind.
Voytik
S L
SL
Henkin
J
J
Burke
S
S
Sasahara
A A
AA
Simmons
A
A
D000818:Animals; D001780:Blood Coagulation Tests; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D007269:Injections, Intra-Arterial; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D010958:Plasminogen / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D013927:Thrombosis / Q000188:drug therapy*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use*
D010446:Peptide Fragments; C018998:lysyl-plasminogen; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator