Abstracts 915

D. E. FttzGerald and E. P. Frisch (Vascular Medicine Unit, St. Mary's Hospital, Dublin, Ireland) : C- W Ultrasound Evaluation of Chronic Peripheral Arterial Disease Treated by i. v. Brinase. (427) Fortyfour patients with chronically obstructed peripheral arteries have been treated intravenously with brinase. Twentyfour of these patients had rest pain or gangrene (Stage III or IV) and 20 were claudicants (Stage II). Assessment before and after treatment was by clinical evaluation, blood pressuro measurement in the limbs, and 0-W ultrasound scanning of the peripheral arteries (Three arterial segments in each limb). Individual dosage requirement was decided by th3 level of brinase inhibitors in plasma. The more severely diseased patients were anticoagulated with Warfarin. The follow-up period from treatment extends from six months to three years. At the end of brinase treatment, good clinical improvement was obtained in 11/20 Stage II, 10/12 Stage III and 6/12 Stage IV. The arm-leg blood pressure gradient before treatment in Stage II was 88±41 mmHg, in Stage III 108±43 mmHg, and in Stage IV 129 ±45 mmHg. In patients responding to brinase treatment (27/44) a post-treatment gradient of 44 ±27 mmHg was recorded. In patients who failed to improve the higher gradient of 81 ± 49 mmHg was retained. 0-W ultrasound scanning of 228 arterial segments before treatment showed that 67 segments were occluded, 101 stenosed and 60 segments without significant lesions. Following treatment 19 segments re mained occluded, 122 showed stenosis and 87 were without significant lesions. The post-treatment figures indicate a reduction in severity of arterial lesions.

8. Ekestrom, E. P. Frisch, F. Ltmd and F. Magaard (Thoracic Surgery Department, Karolinska Hospital, Stockholm, Sweden): Brinase Treatment of Advanced Obliterative Arterial Disease. ( 428) Thirtyfive patients with chronic peripheral arterial disease (10 Stage II, 23 Stage III and IV, 2 acute oeeluRions) were treated with brinase. Arteriosclerosis was the cause of disease in 27 patients, 8 had non-arteriosclerotic obstructions (5 thrombangiitis obliterans, 2 necrotizing vasculitis and 1 systemic lupus erythematodes). Twentyfive patients received full series of brinase treatment, in l 0 patients treatment was discontinued (4/10 of reasons related to treatment). Twenty patients were treated by i. v. brinase infusions. Dosage was based on determina- tion of the brinase inhibitor capacity in plasma. In 5 cases brinase was instilled intra- arterially during vascular surgery, treatment was continued by i. v. brinase infusions. All patients except two were anticoagulated (dicoumarol and/or heparin). After initial arteriography the patients were followed by peripheral blood pressure measurement and in part by dynamic fluorescein angiography. Patients, treated peroperatively with brinase, were examined by electromagnetic flowmetry. At termination of brinase treatment 20/25 patients showed clinical improv8ment. Increase of flow in the superficial femoral artery was recorded after peroperative intra- arterial instillation of brinase. The blood pressure gradient (arm-leg) before treatment (25 patients) was 112±24 mmHg. In patients with arteriosclerotic obstructions showing clinical improvement (14/19) the gradient was lowered to 49 ±20 mmHg, as compared This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. to 112 ±27 mmHg in clinical failures. In patients with non-arteriosclerotic occlusions (6/6 improved) the gradient was lowered to 32 ±21 mmHg. Fluorescein angiography indicated improved m i crocirculation. Bleeding complications were not observed.

E . P. Frisch, M. Blombdclc and H. Kiessling (Med. Dept., AB Astra, Si.idertalje, Sweden) : Dosage of i.v. Brinase in Man Based on Determination of the Brinase Inhibitor Capacity and Coag·ulation Studies. (429) Brinase, a proteolytic enzyme from Aspergillus oryzae, is in plasma inhibited by two· endogenous inhibitors. In vitro addition of the enzyme to plasma lowers the brinase 916 Abstracts inhibit::>r capacity (BIC); the calculated regression line was used to predict lowering of BIC resulting from i. v. infusion of brinase in man. A total of 355 i. v. brinase infusions (single doses of 50- 200 mg) were given to 36 patients suffering from advanced peripheral arterial disease. Anticoagulant treatment (dicoumarolor heparin) was given concomitantly to 34/36 patients. BIC was determined by the azocollagen method before and after infusion of the enzyme. Good correlation was found between calculated lowering of BIC and determined post-infusion values. Individual dose require- ments could be calculated and free proteolytic activity by depletion of inhibitors was avoided. the Changes of ()( 1-antitrypsin and ()( 2 -macroglobulin induced by brinase infusion showed same trends as those recorded for BIC; there was no quantitative correlation. Fibrinogen was lowered by infusion of the enzyme, subnormal values were determined at 4 occasions. There was a moderate increase of fibrinogen degradation products and thrombin time was prolonged. Positive ethanol gelation t est following brinase infusion was a constant finding. Brinase induced slight lowering of Thrombotest values and prolongation of the activated part-ial thromboplastin time; dosage of anticoagulants was not influenced. Other coagulation tests showed insignificant chauges only. In two patients, not on anticoagulants, with a history of renal disease, transient renal failure occurred subsequent to brinase infusion. Laboratory data indicated intravascular coagulation as a possible cause. Bleeding complications were not observed.

Caroline 1vlcKillop, W. Edgar, G. D. Forbes and G. R. M. Prentice (University Department of Medicine, Royal Infirmary, Glasgow, Scotland): Formation of Soluble Complexes of Fibrinogen Relateancrod infusion were studied. Blood samples were obtained before treatment and after 6 and 24 hours ancrod infusion. Fibrinogen and its derivatives were precipitated with beta-alanine and separated by 6 per cent agarose gel filtration. A range of soluble complexes were demonstrated after 6 hours infusion. Polyacrylamide gel electrophoresis in SDS showed that the soluble complexes were largely composed of units with molecular weight similar to a minimally degraded early Fragment X. Polyacrylamide gel electrophoresis in SDS and mercaptoethanol showed a marked loss of intact alphachain in the soluble complexes when compared with the uncomplexed material, suggesting that the soluble complexes had undergone preferential fibrinolytic digestion. It is suggested t-hat, during ancrod therapy, FDP may be produced directly from soluble complexes rather than insoluble micro-thrombi as has been suggested previously.

G. Lawrence Slade and W. Abe Andes (United States Army Institute of Surgical Research, Fort Sam Houston, Texas 78234): Platelet Aggregation Following Defibrination with Ancrod. ( 431) A transient defect in platelet aggregation was observed following defibrination with Ancrod. Adult mongrel dogs were defibrinated using a slow intravenous infusion of Ancrod. Defibrination was maintained for ninety-six hours. Immediately following d e fibrination there was a complete ablation of the normal platelet response to thrombin or ADP with a gradual return toward normal aggregation over the ninety-six hour period. Fibrin This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. d egradation product titers were highest at the time of maximum inhibition of platelet aggregation. The return to normal aggregation paralleled the fall in the fibrin degradation product titer.

M. Bielawiec, A. Perzanowslci and M. Mysliwiec (Haemoatology Clinic, Institute of Internal Medicine, Me dical School, Bialystok, Poland): Long Term Therapy of Patients Suffering from Occlusive Arterial Diseases with Combined Therapy with Phenformin and Stanozolol. (432) Phenformin (Dibotin-Winthrop) 100 mg daily and Stanozolol (Stromba-Winthrop) 7,5 mg daily w e re given for at least half a year and longer periods to 7 5 patients suffering