156 Impairment of fibrinolysis after PTCA and restenosis

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P O S T E R P R E S E N T A T I O N S : Fibrinolysis in vascular disease I

156 Impairment of fibrinolysis after PTCA and restenosis PRISCO D, CAPANNI M, ANTONUCC1 E, CHIARUGI L, MARCUCC1 R, FARSI A, PEPE G, POLl D, and GENSINI GF lstituto di Clinica Medico Generale e Cardiologia, University of Florence, Florence, Italy Percutaneous transluminal coronary angioplasty (PTCA) is still affected by restenosis in rate of 25-40%. This study was aimed to investigate the acute effect of PTCA on clotting activation and fibrinolytic system and the possible role of modifications of haemostasis in relation to restenosis after PTCA. In 83 selected patients, undergoing PTCA blood clotting and fibrinolytic activation were assayed before and within 60 minutes after the procedure. All patients were on acetilsalycilic acid (ASA) and on standard antianginal treament; during the procedure 0.5 g ASA and 10.000 IU heparin i.v. were infused in all patients. Patients were clinically followed up for a mean time of 20 months and angiography was again performed in those who suffered from recurrent anginal attacks or had a positive ergometric test. At the end of the procedure there was a significant decrease in plasma levels of fibrinogen, fragment 1+2 of prothrombin, thrombinantithrombin complexes (p < 0.0001), plasminogen activator inhibitor I (PAl- 1), tissue-type plasminogen activator antigen (t-PA) and euglobulin lysis time (ELT). D-dimer had a significant increase (p<0.0005). As showed in table, patients with restenosis had signs of lower fibrinolytic activation after PTCA.

ELT (In's) before PTCA afterPTCA PAl- 1 before PTCA (IU/mL) after PTCA t-PA before PTCA (n~Im8) after PTCA

Total (n=83)

No restenosis Restenosis (n=70) (n=13)

6.5 (2-10) 5.0(1.5-12)***

6.5 (2-10) 7.0 (3.5-10) 4.6(1.5-10)*** 16.0(3-12)§

8.2 (3-30.1)

8.3 (3.1-30.1)

8.0 (3-24.2)

5.3 (3-23.2)***

5.0(3-22.4)***

9.4 (4-23.2)* §§

8.5 (4.4-21.6)

8.5 (4.4-21.6)

8.5 (5.2-13.2)

7.5 (4.5-16.6)** 8.0 (4.5-16.6)*

6.0 (5-9.3)* §§

*p<0.05, ** p<0.001, *** p<0.0001, vs base-lines; § p<0.05, §§ p<0.0005 vs no restenosls patients These results suggest that heparin administered during PTCA is able to blunt blood clotting activation and that the fibrinolytic response to balloon injury, by determining "per se" a longer local persistence of thrombus and by triggering a release of mediators involved in the proliferation of smooth muscle cells, is a relevant determinant of the risk of restenosis after PTCA.

m

157 Effect of a low osmolality nonionic contrast medium on thrombin generation and fibrinolysis in patients subjected to coronary angiography GORSK1 J, FLASINSK1 J, KUREK P, and B1RKHOLZ-GOLASZEWSKA A Institute Maritime Medicine, Gdynia, Poland The relatively w e a k anticoagulant and antiplatelet effect of nonionic contrast media ( N I C M ) m a y not prevent additional t h r o m b o e m b o l i c deposits in pts subjected to coronary angiography. The aim o f o u r study was to demonstrate the effect o f N I C M (iopromide) injected into coronary artery on thrombin generation: thrombinantithrombin III c o m p l e x e s (TAT), p r o t h r o m b i n fragment 1+2 ( F l + 2 ) and fibrinolysis: p l a s m i n o g e n activator (PA) and plasminogen activator inhibitior ("active" PAI-1).

RESULTS A B

PA 2.4±0.4 2.1±0.6

PAl* 11±4 16±5

TAT* 3.7± 1.3 5.4±1.5

FI+2* 1. I±0.4 1.7±0.5

*p < 0.05 C o n c l u s i o n . The use of iopromide results in increase of thrombin generation and activity as well as in increase of PAI activity; demonstrated alterations m a y intensify prothrombotic reactions and t h r o m b o e m bolic deposition.

The blood f r o m 38 pts after A M I w a s collected during elective coronary angiography using J u d k i n ' s catheter w a s h e d only with 0.9 % N a C l j u s t before (A) and 3 rain. after (B) the application of 50-70 ml o f Ultravist-370. T A T (Boehringer M a n n h e i m ) , F1 +2 (Behring), PA and PAI ( O r g a n o n Teknika) were m e a s u r e d by E L I S A micromethod. m

158 Fibrinolytic response to venous occlusion compared to exercise stress in young patients with coronary artery disease and

healthy controls *N1KFARDJAM M, *GRAF S, **BECKMANN R, *KOLLER-STRAMETZ,1, *HORNYKEWYCZ, **BINDER BR, and *HUBER K Departments of Cardiology, and Vascular Biology and Thrombosis Research*. University of Vienna, Austria Background. It has been demonstrated, that venous occlusion (VO) and exercise stress (ES) stimulate the fibrinolytic system. Aim of this study was to answer which type of stimulation is more useful in patients who are symptom-limited. Methods and Results, We investigated 20 patients (pts M/F=IS/5; mean age:36.7 years) with angiographically proven coronary artery disease (CAD) for their plasma levels of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-type-1 (PAI-I) at basal conditions and after VO and before and after ES (standardized bicycle stress test) and compared the data obtained to those from 12 sex- and age-matched healthy controls (ctr M/F=gl3) as well as between the different stimulation tests. At basal conditions mean t-PA activity and t-PA antigen plasma levels were within the normal range and comparable between the two study groups. After both VO and ES, mean t-PA activity (p--0.015 and p--0.003, respectively) and

t-PA antigen levels (p--0.045 and p=0.53, respectively) increased significantly more in the control group as compared to the CAD group. Mean PAl- 1 activity plasma levels were significantly higher in the CAD group at basal conditions before VO (pts 7.0-'-3.1; ctr 3.9+-3.9; IU/ml; p=0.025) as well as before ES (pts 8.1 ±3.5; ctr 4.3+-3.8; IU/ml; p--0.009). As can be seen, no significant alteration of any of the basal fibrinolytic parameters could be detected for the time interval (6 weeks) between performance of VO and ES. PAl-1 activity plasma levels showed a significant decrease for patients and controls only after VO (p--0.038), while PAl-1 activity was not signifi' candy decreased in both study groups after ES. The significantly higher increase in mean plasma levels of t-PA activity and t-PA antigen after VO compared to ES in both groups (p--0.0005 and p < 0.0001, respectively) might be explained by the fact that CAD patients were limited to symptoms and could perform only 80% of their age, sex, body mass index related optimal work load. Conclusion. VO and ES are applicable triggers of the endogenous fibrinolytic system in healthy subjects and patients who are not limited to physical exercise. VO appears to be superior to ES as stimulation test of the endogenous fibrinolytic system in patients with symptomatic CAD.