Streptokinase and rt-PA activate platelets by a different way: implications on the rethrombosis rate after their administration in myocardial infarction

74 Strategies zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFED POSTER PRESENTATIONS P-7: Thrombolytic 203 STRONG ANTI-PLATELET FIBRINOLYSIS-POTENTIATING MUSHROOM EXTRACTS AGGREGATION ACTIVITIES AND IN Induced by ADP, twice more than that of Shiitake (Ebanix zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA PAM-6C aggregation analyzer). One-fortieth volume of zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA (Pleurofus osfrcatus and the extract added to PRP completely inhibited primary Lenthus edodes ). Sumi H, Matsubara K, Yatagai C. ‘Ishii K and ‘Fujoka T Department of Nutrition, Faculty of Health and Welfare Science, Okayama Prefectural U&e&y, So&shi, Okayama 719-11. ‘Biotechnology Research Institute. Asano-sangyo Co. Ltd.. Tamano-shi. Okayama. Japan. and secondary aggregation induced by ADP. Since the substance maintaind more than 90% of activity after lh. it was extracted from boiled boiling at 100°C: for Hiratake treated with one-hundred of enzyme (Asp. niger cellulase and Rhizopus sp. enzymes; SMIZYM AC and MC wet/wet). The supernatant (ASK-1L) , obtained after centrifugation strongly inhibited human platelet aggregation induced not only by ADP but also collagen and thrombin. Lyophilized ASL-IL administrered p.o. (5.8mg /kg body wet.) to rat, after l-5h. decreased platelet aggregation and increased fibrinolytic activity of EFA. Scince mushroom extract is common food for human, it was safe to eat. Seven volunteers, 18-48 years of age, were given lyophilized ASK-1L with 500mg/kg body. After 3h, the platelet aggregation was decreased, and fibrindytic activity of EFA was accelerated because of the increase of t-PA like plasminogen activator (mdwt. 70-100 kDa) in plasma. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA It is well known that in mushurooms. there are various biologically active substances lowering blood pressure, restraining obesity, Inhibiting tumoer cell growth and are anti-HIV. We have found the fibrinolytic enzymes in traditional fermented foods or marine creatures (Sumi. et 43: 1110. 1987; Comp. Biochem. Physiol. al Experientia 1028: 163, 1992). In the present report, we found that the heated extract from Hiratake (Pfeurotus ostreatus ) and Shiitake (Lentinus edodes 1 had anti-platelet aggregation and acceleration of fibrinolytic activity. Mushuroom (Asano-sangyb Co. Ltd.) was homogenized The soluble with 10 volume of distilled water (wet/vol). extract of Hiratake inhibited human platelet aggregation activator inhibitor-l (PAI-1) and the generation of thromboxane (TxB*), Main BY A 204 STREPTOKINASE AND &PA ACTIVATE PLATELETS zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA DIFFERENT WAY: IMPLICATIONS ON THE RETHROMBOSIS RATE AFTER THEIR ADMINISTRATION IN MVOCARDIAL INFARCTION. P Parise, A lorii, J Hauert’ and G Agnelli. Fromt/~he lnslituteof fntemal and Vascular Medicine, Univereily of Peru ia, ka/y and ‘Division of Hemabfogy, results are shown in the table: University Hospifal Center, CH 9/ V, Lausanne, Switzerland. The natural history of acute myocardial infarction has been dramatically changed by the advent of thrombolytic treatment with a 30% mortality reduction, a better recovery of ventricular function, and a better quality of life. Notwithstanding, failure or delay in achieving reperfusion, reocclusion and bleeding still worries clinicians and challenge researchers to improve lhrombolytic regimens and concomitant antithrombotic treatments. Platelet activation, at least in part due to thrombolytic treatment itself, plays a pivotal role in the pathogenesis of resistance to lysis and rethrombcsis. Aim of this study was to compare in vitro the effects on platelets of therapeutic concentralons of streplokinase (SK) and rt-PA. The effects of plasmin (Pli) and thrombin (Thr) were also studied as reference. We used fluorescence flow cytometry to evaluate: a) fibrinogen binding (FB); b) surface ixpression of GMP-140, which is a sensitive marker of platelet release reaction. Platelet function was further studied by measuring the release of 14C-serotonin (Ser), O-thromboglobulin (O-TG), plasminogen 205 Recanalization of acute occlusion after percutaneous transluminal coronary angioplasty (PTCA) using a synthetic thrombin inhibitor, argatroban Matsuo T, Kario K, Suzuki T, Miki T, Sakamoto Department of Internal Medicine, Hyogo Awaji Hospital, Sumoto, Hyogo, Japan S. Prefectural The incidence of restenosis after PTCA for angina pectoris could be reduced by use of argatroban instead of heparin. Administration of argatroban was estimated to provide the same degree of prolon ation of APTT as heparinization during and after PT 8 A for a week. In adjunctive therapy with heparin, significant increase of thrombin-antithrombin III (TAT) was detected during and after PTCA and a higher incidence of restenosis occurred in patients with increased levels of TAT. As a substitute for heparin in PTCA, argatroban could prevent the incidence of restenosis after PTCA. Also, argatroban inhibited the activation of fibrinogen and maintained a lower plasma levels of fibrinogen activity than that after heparin administration. Our data showed lhat plasmin,, even at low concentrations, and SK stimulate fibrinogen receptor expression and a-granule secretion. SK-induced platelet activation is rapidly followed .by a platelet function impahment mainly due to platelet degranulation. On the other hand rt-PA, even at therapeutic concentrations, selectively promotes fibrinogen binding. These results, coupled with the less pronounced lytic state induced by &PA, could explain the higher incidence of reocclusion showed by rl-PA in comparison with SK in absence of an effective “adjunctive” antithrombotic treatment. No thrombolylic agent activates arachidonate pathway. Thus aspirin is probably far from being the ideal antiplatelet agent to be used conjunctively with thrombolytic agents. Newer approaches, particularly RGD peptides and antibodies against GP Ilb/illa, could produce better results. Present study investigated whether argatroban inhibited acute occlusion induced by PTCA. Subjects were chosen from 84 consecutive case of elective PTCA for angina pectoris. Four cases were unsuccessful after repeated PTCA because of acute occlusion following recanalization of coronary artery by PTCA. These procedures ordinary include heparinization and they immediately had thrombolysis with urokinase could not obtain any reperfusion. After confirming the absence of reperfusion by angiography, a 5 mg bolus of argatroban was infused via catheter followed by 5-10 mg/h continuous infusion for one week. The dose of argatroban was adjusted to include 1.5 times prolongation from the base line. As a result, all acute occlusion was resolved immediately after the Infusion of argatroban and there was no sign of recurrence or symptom of myocardial ischemia during argatroban infusion. For treatment of acute occlusion after PTCA, argatroban was effective for recanalization of coronary artery through inhibition of thrombin generation.