title: Comparison of local thrombolytic efficacy of plasmin and rt-PA in an in-vitro flow system; a pilot study.
abstract: Plasmin, a directly acting thrombolytic agent, demonstrated a very favorable safety profile upon intra-arterial delivery to the clot site; however, its thrombolytic efficacy remains to be further assessed. In this study, differences in thrombolysis between clots exposed to equimolar concentrations of plasmin and recombinant tissue-type plasminogen activator (rt-PA) after partial vessel recanalization were tested in a model system. Model blood clots were prepared in glass chambers enabling direct observation by dynamic optical microscopy. The incubation of clots with plasmin (2.4 mg/ml) or rt-PA (2.63 mg/ml), allowing for the initial biochemical clot degradation, was followed by 'flushing' the clots with tangentially directed plasma flow devoid of a thrombolytic agent, mimicking blood flow after partial vessel recanalization. The acquired images were analyzed for nondissolved blood clot area as a function of time. With both thrombolytic agents, the relative clot area decreased rapidly in the first 30 s after initiation of perfusion due to 'flushing' the degraded clot fragments (after plasmin by 0.26 ± 0.22 and after rt-PA by 0.34 ± 0.21, P = 0.60). In the following minutes, the clot size showed a linear time dependence: after incubation with plasmin the clot size did not change substantially any more, whereas after incubation with rt-PA the clot size continually decreased. The slopes of the regression lines differed significantly (r(pl) = -8.9 10 vs. r(rtPA) = -44.1 10/min, P < 0.01). In conclusion, the thrombolytic action of plasmin was terminated rapidly by contact with flowing blood plasma, whereas the thrombolytic action of rt-PA was prolonged.
authors.affiliation: aJožef Stefan Institute bInstitute of Physiology, Medical Faculty of Ljubljana cDepartment of Vascular Diseases, University of Ljubljana Medical Center, Ljubljana, Slovenia dDivision of Hematology/Medical Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California eGrifols, Inc., Research Triangle Park, North Carolina, USA fEN-FIST Centre of Excellence, Ljubljana, Slovenia.
authors.forename: Nina
authors.initials: N
authors.lastname: Bizjak
authors.forename: Franci
authors.initials: F
authors.lastname: Bajd
authors.forename: Jernej
authors.initials: J
authors.lastname: Vidmar
authors.forename: Aleš
authors.initials: A
authors.lastname: Blinc
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Marder
authors.forename: Valery
authors.initials: V
authors.lastname: Novokhatny
authors.forename: Igor
authors.initials: I
authors.lastname: Serša
mesh_terms: D005341:Fibrinolysin / Q000008:administration & dosage*; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D008853:Microscopy / Q000379:methods; D010865:Pilot Projects; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000097:blood
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin