title: Resistance of porcine blood clots to lysis relates to poor activation of porcine plasminogen by tissue plasminogen activator.
abstract: In-vitro experimentation was performed on porcine and human blood to determine their comparative responsiveness to a novel fibrinolytic inhibitor and thereby assess whether the pig is a suitable animal model for subsequent in-vivo testing of this inhibitor. Thromboelastography showed the clots formed from porcine whole blood to be highly resistant to tissue plasminogen activator (t-PA)-catalyzed lysis, and this communication offers the resistance of porcine plasminogen to activation by t-PA as an explanation. Porcine blood containing 100 and 1500 IU/ml added t-PA lysed very slowly, having LY30 values of 1.9 +/- 1.4 and 2.9 +/- 1.9%, respectively. In contrast, the LY30 values for the human clots containing 100 and 1500 IU/ml t-PA were 77.1 +/- 6.3 and 93.3 +/- 1.3%, respectively. Moreover, purified porcine plasminogen was activated very slowly by added t-PA in the presence of both human and porcine fibrin. Activation of plasminogen by the endogenous activators, as measured by the euglobulin clot lysis time, was greatly prolonged for the pig (22 +/- 3 h) compared with the human (3.5 +/- 1.5 h). These results suggest caution in using the pig as an experimental model when studying the effects of various agents on fibrinolysis.
authors.affiliation: School of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia. sflight@soms.uq.edu.au
authors.forename: Simone M
authors.initials: SM
authors.lastname: Flight
authors.forename: Paul P
authors.initials: PP
authors.lastname: Masci
authors.forename: Martin F
authors.initials: MF
authors.lastname: Lavin
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Gaffney
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D023421:Models, Animal; D010958:Plasminogen / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012712:Serum Globulins / Q000737:chemistry / Q000378:metabolism; D013552:Swine; D013916:Thrombelastography; D013927:Thrombosis / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D012712:Serum Globulins; D010958:Plasminogen; D010959:Tissue Plasminogen Activator