CORONARY THROMBOLYSIS

187 188 REPERFUSION \r.lNTRICULAR FIBRILLATION, CORONARY FLOI:I fulD FIBRINOGEN DOSAGE AS A SYSTEMIC MARKER OF UNSUCCESSFUL INTRA­ PHARMACOLOGIC PREVENTION. J. Cosin, A. Hern8ndiz, T. Caffarena, VENOUS STREPTOKINASE IN ACUTE MYOCARDIAL INFARCTION F. Andres, A. Cabades, J. L. Diago. Centro de Investigaci6n La Fe, Valencia. Spain. Ch. Col-De Beys (1), E. Lavenne-Pardonge (1), M. Moriau (1), J. Renkin (2), J. Col (2). Haemostasis Unit (1) Coronary Care Reperfusion ventricular fibrillation (aVF) might be involved Unit (2) - St Luc University Hospital - BRUSSELS - BELGIUM in sudden death. A reliable model for the evaluation of the prevention of RVF does not exist and published results Whether failure to timely recanalize coronary artery with in­ vary greatly. To investigate: a) the relationship between travenous streptokinase (SK) is related to inadequate fibrinoly­ coronary flow and RVF and b) pharmacologic prevention of sis remains controversial. Since coagulation might also interfe­ RVF, two experimental series have been performed. re with the course of clot lysis, this relation was investigated a) Ultrasonic flow-meters were implanted in the circumflex in 27 patients (pts) pretreated with heparin (10.000 IU bolus). coronary artery (cca) of 19 anaesthatised open chest dogs. 500.000 to 1.500.000 IU SK were infused in 45 min, 160 ± 60 min after the onset of infarct. In each dogs several occlusion/reperfusion procedures on the cca, were performed. b) Two occlusion/reperfusion Angiographic control, performed 219 ± 199 min after SK, showed procedures of 10' on the cca were performed. In each experience persistent coronary occlusion in 5 pts (OCC) and patency in 22 the first reperfusion acted as a control of the drug's (PAT), unrelated to SK dosage. One to 3 hours post SK, fibrino­ effects on the second reperfusion. The procedure was followed gen (Fg) (Clauss Method) was undetectable in all 22 PAT and 4/5 in 54 dogs with controls of epicardium and surface ECG, OCC. However, Fg (and clottable breakdown products) assessed by cca blood flow (n = 24) and right anC left intraventricular Gram's method* was detected in all 5 OCC and 3/22 PAT (164 ± 89 pressures. Phentolamine (0.30 mg/kg), Quinidine (8 mg/kg), VS 13 ± 38 mg %, p < 0. 005). Prolongation of thrombin time (neu­ Nifedipine (0.16 mg/kg), Verapamil (0.25 mg/kg}, Dipyridamole tralized with protamine) was limited in OCC, compared to PAT (0.40 mg/kg), were injected intravenously. (59± 6 VS 96 ± 11 sec, p < 0.005), supporting the hypothesis of After removing the obstruction, increases in coronary the presence of clottable material in OCC. These results were ac­ flow were produced, reaching a mean maximum of 215.1% over companied by slight differences of ELT (< 20 min in 2/5 OCC VS the basal flow ( p <: 0. 001) . The RVF' s appeared between 2 21/22 PAT) and non significant differences in plasminogen (1.78 and 16 seconds ( 9. 4 ± 6. 8 sees) after the beginning of ± 1 VS 2.18 ± 1.1 mg/dl ; NS), o<2 antiplasmin (1.7 ± 1.7 VS 3.9 2 reperfusion, when coronary perfusion had reached 73% above ± 6.9% ; NS), plasmin (12 ± 4 VS 16 ± 11 mm ; NS) and plasmino­ 2 the basal flow (p <. 0.001) and had not reached the theoretical gen activators (95 ± 41 VS 105 ± 23 mm ; NS). maximum flow. The speed of the reperfusion was no a Conclusion : at similar systemic lytic activity induced by SK, determinating factor of the arrythmia. failure of arterial recanalization was associated with an appa­ Only Dipyridamole significantly prevented the incidence rent incomplete fibrinogenolysis (and fibrinolysis) in 20 % of of RVF in the second reperfusion in regards to the first the patients. ( p < 0. 01). Dipyridamole produced a greater increase in *Gram H.C. - A new method of determination of the fibrin percent basal flow (128.4% ± 70.7) and reperfusion flow (360.5% in blood and plasma - J Biol Chern 49 : 279 - 295 ± 181). (1921) Dipyridamole had a preventive effect of experimental RVF. This action may be a consequence of its effects on mean ± SD coronary flow.

189 190 STREPTOKINASE- INDUCED, ANTI BODY -MED lA TED PLATELET AGGREGATION: A POTENTIAL CAUSE OF CLOT PROPAGATION IN VIVO. D.E. Vaughan and J. Loscalzo. Brigham and Women's Hospital and Harvard Medical School, Boston, MA, U.S.A. We identified a patient who exhibited paradoxical propagation of thrombus coincident with the administration of intracoronary streptokinase (SK) that was mediated by anti-SK antibodies. The The new drug pro-urokinase, a proenzyme of urokinase (scu­ patient had not been treated with SK in the past and had a plasma PA), seems to have advantages in comparison with other fibrino­ SK-neutralizing capacity of 160 U/ml. Using platelet-rich plasma lytic agents. Properties like higher fibrin specifity, non­ (PRP) obtained from the patient, we found that SK initiated systemic activity and lower antigenity may lead to a lower rate spontaneous platelet aggregation and secretion in vitro. Aggre­ of complications. In a pilot study 10 patients with acute myo­ gation was specific for SK and not induced by urokinase or tis­ cardial infarction have been treated under angiographical control sue plasminogen activator. In 14 of 15 controls, no platelet with pro-urokinase (3- 9 millions IU) by i.v. application. In aggregation was observed in PRP with addition of SK. The addi­ case of no perfusion a further administration of streptokinase tion of plasma or purified IgG from our index case to the PRP was carried on. The blood samples were obtained at therapy begin of all 14 controls supported SK-induced aggregation. This aggre­ and after 5, 10, 30, 60 and 120 minutes. The therapy monitoring gatory response was not inhibited by aprotinin. Using purified This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. was performed by determination of established haemostasis para­ proteins in a washed platelet system, we found that platelet ag­ meters, like fibrinogen, fibrin(ogen)-split products (FSP), a2- gregation was dependent on the presence of SK, specific anti-SK antiplasmin. Plasminogen and batroxobin-time. Furthermore, the lgG, plasminogen, and platelets. These data demonstrate that diagnostic relevance of new laboratory tests for fibrinolysis, anti-SK antibodies can promote platelet aggregation, presumably D-Dimer and thrombin-antithrombin III-complex (TAT) has been by binding to platelet-bound plasminogen-SK complexes. These investigated considering some typical follow-ups. D-Dimer were data also imply that some individuals may possess anti-SK anti­ determined by latex agglutination test and TAT by enzyme immuno­ bodies that are capable of inducing platelet aggregation in vivo assay. and, thereby, promoting clot propagation or thromboembolic compli­ cations. In the absence of adequate, specific screening, this Generally the application of pro-urokinase in contrast to strep­ observation argues for the use of nonimmunogenic thrombolytic tokinase results in minimal changes of the classic fibrinolysis agents in the emergent setting. parameters like fibrinogen, FSP, batroxobin-time etc. demonstra­ ting no systemic lysis. The appearance of plasmic degradation products of cross-linked fibrin (D-Dimer) is a specific indi­ cater of the release of thrombotic material. Other non-specific degradation products (fibrinogenolysis) were detected by the measurement of FSP. In some cases in which perfusion ocurred an increase of TAT followed by a rapid decrease was observed. This indicates a higher thromboplastic activity which may ori­ ginate from the infarcted area producing TAT complex formation.

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