Changes in Fibrinolytic System after Continual Doppler Monitoring in Healthy Volunteers

Česká verzia

Authors: D. Školo udík ^1,3; T. Fadrná ¹; M. Bar ¹; O. Zapletalová ¹; O. Zapletal ²; J. Blatný ²; K. Langová ³ ; D. Šaňák ⁴; M. Král ⁴; R. Herzig ⁴; P. Kaňovský ⁴
Authors place of work: Neurologická klinika FN Ostrava, 2Oddělení klinické hematologi e, Dětská nemocnice FN Brno, 3Iktové centrum, Neurologická klinika LF UP a FN Olomo uc, 4Oddělení bi ometri e, Ústav lékařské bi ofyziky LF UP v Olomo uci ¹
Published in the journal: Cesk Slov Neurol N 2009; 72/105(5): 446-452
Category: Original Paper

Summary

Background:
In vitro and in vivo studies have demonstrated that ultrasonic waves at a frequency of 20 kHz–2 MHz enhance the lysis of thrombus brought on by thrombolytics. The aim of this study was to demonstrate that the application of continual 60-minute ultrasonic monitoring (sonothrombolysis, ST) using a transcranial 1–4-MHz probe brings on activation of a patient’s fibrinolytic system when monitoring both middle cerebral artery (MCA) and radial artery (RA).

Material and methods:

Thirty volunteers participated in the study and underwent ST of MCA (ST-MCA), ST of RA (ST-RA) and a standard neurosonological examination (SNE) at two-week intervals. The following parameters were examined prior to, 60 minutes and 24 hours after the ST-ACM, ST-AR and SNE: tissue plasminogen activator (tPA), PAI-1 antigen, α-2-antiplasmin (AP), plasminogen (PG), thrombocyte count, fibrinogen level, D-dimers, fibrin degradation products (FdP), fibrin monomers (FM), aPTT, prothrombin time, time of euglobulin lysis, osmolality, homocysteine and lipoprotein (a). Neurological and physical examination was done prior to, 60 minutes, 24 hours, 30 days and 90 days after ST-MCA, ST-RA and SNE. All adverse effects were recorded. An MR examination of the brain was done on all volunteers before the ST-MCA was started as well as 24 ± 4 hours after the end of monitoring. The paired Student’s t-test, a non-parametric Wilcoxon Signed rank-Test and Friedman’s ANOVA test were used to execute statistical assessment of the changes in values of the monitored parameters.

Results:
Following the ST-ACM there was a significant decrease in PAI-1 antigen of 26.6%, in AP activity of 5.1%, in PG activity of 4.3% and in tPA antigen of 7.1%. Following the ST-Ar there was a significant decrease in PAI-1 of 16.8%, in AP activity of 3.3%, and in PG activity of 6.7%. Following the SNe there were no significant changes in any of the monitored parameters. The MR examination of the brain did not demonstrate any detectable changes compared to the initial examination in any of the volunteers.

Conclusion:
Transcranial Doppler monitoring of the flow capacity of brain and upper limb vessels by way of a diagnostic duplex transcranial probe leads to a direct effect of the fibrinolytic system accompanied by a decrease in the level of fibrinolysis inhibitors.

Key words:
ultraso und – tre atment – fibrinolytic system – transcrani al Doppler – transcrani al probe

Zdroje

1. Daffertshofer M, Fatar M. Therape utic ultraso und in ischemic stroke tre atment: experimental evidence. Eur J Ultraso und 2002; 16(1– 2): 121– 130.

2. Francis CW, Onundarson PT, Carstensen EL, Blinc A, Meltzer RS, Schwarz K et al. Enhancement of fibrinolysis in vitro by ultraso und. J Clin Invest 1992; 90(5): 2063– 2068.

3. Alexandrov AV, Demchuk AM, Felberg RA, Christo u I, Barber PA, Burgin WS et al. High rate of complete recanalisati on and dramatic clinical recovery during tPA infusi on when continuo usly monitored with 2- MHz transcrani al Doppler monitoring. Stroke 2000; 31(3): 610– 614.

4. Alexandrov AV, Demchuk AM, Burgin WS, Robinson DJ, Grotta JC. CLOTBUST Investigators. Ultraso und- enhanced thrombolysis for acute ischemic stroke: phase I.Findings of the CLOTBUST tri al. J Ne uro imaging 2004; 14(2): 113– 117.

5. Eggers J, König IR, Koch B, Händler G, Seidel G. Sonothrombolysis with transcrani al color- coded sonography and recombinant tissue‑type plasminogen activator in acute middle cerebral artery main stem occlusi on: results from a randomized study. Stroke 2008; 39(5): 1470– 1475.

6. Školo udík D, Bar M, Škoda O, Václavík D, Hradílek P,Allendoerfer J et al. Safety and Efficacy of the Sonographic Accelerati on of the Middle Cerebral Artery Recanalizati on: Results of the pilot Thrombotripsy Study. Ultraso und Med Bi ol 2008; 34(11): 1775– 1782.

7. Eggers J, Seidel G, Koch B, König IR. Sonothrombolysis in acute ischemic stroke for pati ents ineligible for rt- PA. Ne urology 2005; 64(6): 1052– 1054.

8. Školo udík D, Bar M, Škoda O, Václavík D, Hradílek P,Langová K et al. Účinnost sonotrombotripse a sonotrombolýzy v rekanalizaci střední mozkové tepny. Cesk Slov Ne urol N 2007; 70/ 103(3): 248– 252.

9. Francis CW, Behrens S. Ultrasonic thrombolysis. In: Hennerici M, Me airs S (eds). Cerebrovascular ultraso und: the ory, Practice and Future Developments. Cambridge: University Press 2001: 404– 415.

10. Školo udík D, Fadrná T, Bar M, Zapletalová O, Zapletal O, Blatný J et al. Changes in haemoco agulati on in he althy volunteers after a 1- ho ur thrombotripsy using a di agnostic 2– 4 MHz transcrani al probe. J Tromb Trombolysis 2008; 26(2): 119– 124.

11. Kelly J, Rudd A, Lewis RR, Coshall C, Parmar K, Mo ody A et al. Screening for proximal deep vein thrombosis after acute ischemic stroke: a prospective study using clinical factors and plasma D‑dimers. J Thromb Haemost 2004; 2(8): 1321– 1326.

12. Šaňák D, Herzig R, Školo udík D, Horák D, Zapletalová J, Köcher M et al. The Safety and Efficacy of Continu al Transcrani al Doppler Monitoring in Tre atment of Middle Cerebral Artery Occlusi on in Acute Stroke Pati ents. J Ne uro imaging 2009. Epub ahe ad of print.

13. Wiman B, Collen D. On the kinetics of the re acti on between human antiplasmin and plasmin. Eur J Bi ochem 1978; 84(2): 573– 578.

14. Schleef RR, Loskutoff DJ. Fibrinolytic system of vascular endotheli al cells. Role of plasminogen activator inhibitors. Haemostasis 1988; 18(4– 6): 328– 341.

15. Bartels E, ed. Color- Coded Duplex Ultrasonography of the Cerebral Vessels. Stuttgart: Schatta uer 1999.

16. Daffertshofer M, Gass A, Ringleb P, Sitzer M, Sliwka U, Els T et al. Transcrani al low- frequency ultraso und- medi ated thrombolysis in brain ischemi a: incre ased risk of hemorrhage with combined ultraso und and tissue plasminogen activator: results of a phase II clinical tri al. Stroke 2005; 36(7): 1441– 1446.

17. Reinhard M, Hetzel A, Krüger S, Kretzer S, Talazko J, Ziyeh S et al. Blo od- Brain Barri er Disrupti on By Low- Frequency Ultraso und. Stroke 2006; 37(6): 1546– 1548.