Comparative time course of thrombolysis induced by intravenous boluses and infusion of staphylokinase and tissue plasminogen activator in a rabbit arterial thrombosis model.
Staphylokinase (SAK), a protein with known profibrinolytic properties, has recently given encouraging results in acute myocardial infarction and in peripheral arterial occlusion. The aims of this study were to compare SAK with alteplase (recombinant tissue plasminogen activator rt-PA) in a rabbit arterial thrombosis model, in terms of femoral blood flow kinetics during and after thrombolysis, and to examine the biological effects of systemic fibrinolysis in vivo. We compared two modes of intravenous rt-PA administration, two modes of intravenous SAK administration and three different SAK dose regimens in a rabbit model of femoral artery thrombosis. The main finding was that the infusion of SAK following a single bolus administration gave statistically higher blood flow values than the infusion of the same dose of rt-PA following a single bolus administration (P < 0.05). In this experimental model, we also confirmed that SAK is a fibrin-specific and plasminogen-saving fibrinolytic agent at doses below 0.5 mg/kg. However, at higher doses (1.0 and 1.5 mg/kg), which are above usual therapeutic doses, SAK significantly reduced fibrinogen levels in a dose- and time-dependent manner (P < 0.05). These results indicate that SAK compares favorably with rt-PA in an rabbit arterial thrombosis model, yielding higher blood flow values. Moderate-dose SAK seems to be a fibrin-specific plasminogen activator, but in our model very high doses were associated with a decrease of fibrinogen.
Clinique Cardiologique, Hôpital Necker, Paris, France. varela@ext.jussieu.fr
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Helft
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D000818:Animals; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000473:pathology*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008666:Metalloendopeptidases / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010960:Plasminogen Activators / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000493:pharmacokinetics
D011994:Recombinant Proteins; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus