Effect of ultrasound on enzymatic activity of selected plasminogen activators.
BACKGROUND
Ultrasound has been shown to accelerate enzymatic fibrinolysis with adjunctive plasminogen activators. Additionally, ultrasound is known for interaction with biological substances on molecular level in sonodynamic therapy and sonochemistry. Therefore, we investigated the possibility of ultrasound affecting the biological activity of plasminogen activators used in thrombolysis treatment.


METHODS
Four currently marketed plasminogen activators were evaluated: urokinase, streptokinase, alteplase, and reteplase. The tests were conducted in reconstituted, undiluted plasminogen activator. Each test contained a control and a test sample. The test sample was incubated in a water bath at temperatures of approximately 34 degrees C and exposed to ultrasound for 1h. The control was incubated in the same water bath as the test sample for the same duration but was not exposed to ultrasound. The ultrasound frequency and intensity used for this experiment were 1 MHz and 2.5-3.1W/cm2, respectively. For quantitative measurement of biological activity of the test and control samples of each plasminogen activator either specific chromogenic substrates or the fibrin clot liquefaction time was used.


RESULTS
Student t-test was applied to compare treated vs. control group for each plasminogen activator. The p-value for urokinase, streptokinase, alteplase, and reteplase are 0.43, 0.76, 0.70, and 0.30, respectively.


CONCLUSIONS
Ultrasound with a frequency of 1 MHz and intensities of 2.5-3.1W/cm2 had no statistically significant impact on biological activity of selected plasminogen activators.
Soltani
Azita
A
Pre-clinical Research Department, EKOS Corporation, 22030 20th Avenue SE, Suite 101, Bothell, WA 98021, USA. asoltani@ekoscorp.com
Soliday
Charles
C
D003131:Combined Modality Therapy; D004789:Enzyme Activation; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D010960:Plasminogen Activators / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013300:Streptokinase / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014464:Ultrasonic Therapy; D014465:Ultrasonics; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D011994:Recombinant Proteins; C087896:reteplase; D013300:Streptokinase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator