Thrombolytic activity of chimeric recombinant plasminogen activators in rabbits

Suppl. XIII, 1991

ABSTRACTS

59

117 THROMBOLYTIC ACTIVITY OF CHIMERIC RECOMBINANTPLASMINOGEN ACTIVCITORS IN RABBITS. M.Colucci, G.G.Nenci, A,Mele, R.Burgi, G.Clonelli, C.Pascucci Istituto di Semeiotica Medica, University of Perugia, J.Heim. Italy; Istituto di Patologia Generale, University of Bari, Menarini Italy; Ricerche Sud, Pomezia, Italy; Ciba-Geigy, easel, Switzerland. The aim of this study was to evaluate the thrombolytic activity of plasminogen activator (PFI) in a rabbit two hybrids (Hs) jugular vein thrombosis model. HP&s linked the kringle 2 domain (Kilt-uPA) and the finger and kringle 2 domains (FK2t-uPA) of t-PA respectively to the catalytic protease domain of scu-PA.The thrombolytic activity of the two HPAe were with rt-PA on a weight/weight basis. Saline served as a control. compared K2t-uPA, FK2t-uPA and rt-PA were infused at doses of 0.4, 0.8 and 1.2 mg/Kg Saline produced 11x22 thrombolysis. The three doses of K2tover 3 hours. 66X+5 and %9X?? thrombolysis, UPA produced 38X+4, respectively. The three 18X+3, 29%+5 and 33X+6; the three doses of rt-PA 32X&2, doses of FK2t-uPA: 49X+3 and 72X+6. Thus K2t-uPA and rt-PCI showed a statistically significant higher thrombolytic activity than FK2t-uPA at the three tested doses (p The thrombolytic activity of K2t-uPA was significantly higher than (0.0011. rt-PFI at the two higher doses (~(0.001). K2t-uPCI and rt-PA produced a statistically significant reduction of fibrinogen (F),alpha2-antiplasmin (AP) and plasminogen (P) after 3 hours of infusion of the highest dose; no differences were found between the two HP&. The systemic proteolytic of FK2t-uPA were less pronounced.We conclude that the two HPAs we effects tested are effective thrombolytic agents and K2t-uPA deserves particular in future experiments. attention

118 THE

COMPfiRATIVE EFFECT

IMPROVING

t-PA

INDUCED

OF RECOMBINANTHIRUDIN AND

THROMBOLYSIS

IN

RABBITS.

STANDFIRD G_,A_qpz+~+~,

HEPFIRIN

ON

C.Pascucci, of Perugia,

Istituto di Semeiotica Medica, University G.G.Nenci. B.Cosmi, 06100 Perugia, Italy. hepar in and of this study was to compare the ability of The aim plasminogen recombinant hirudin (r-hirudin) in enhancing tissue-type induced thrombolysis and preventing fibrin accretion on (t-PA) activator experimental thrombi during thrombolysis with t-PA in a rabbit jugular vein Heparin and r-hirudin were infused at doses capable of thrombosis model. infused with saline produced 0.4, and 1 mg/kg, t-PCI, 0.2, doubling aPTT. 52%+5 and 79X+8 thrombolysis, respectively. The same doses of t-PA 34x26, 0.75 mg/kg, produced 32X+3, ‘54%+S and 7B%f6 with heparin, infused and infused with r-hirudin, 1.25 mg/kg, 38x23, respectively; thrombolysis, Thus, no differences in thrombolysis were 57x25 and 82x&a, respectively. r-hirudin and heparin, observed among the groups of rabbits treated with In the thrombus growth inhibition saline receiving the same dose of t-PA. experiments t-PA was infused at a dose of 0.2 mg/kg along with saline or the above mentioned doses of heparin and r-hirudin. In rabbits treated with heparin or r-hirudin, an accumulation of 125I-fibrinogen t-PA plus saline, was observed, 49.5pg+5.6 and 23.5pg?r3.5 on the thrombi of 52.5pg25.1, the difference between hirudin and both saline and heparin respectively, The inhibition of fibrin (p