Francis C W, Blinc A, Lee S, Cox C
Department of Medicine, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Ultrasound Med Biol. 1995;21(3):419-24. doi: 10.1016/0301-5629(94)00119-x.
Fibrinolysis is accelerated in vitro in an ultrasound field, and externally applied high frequency ultrasound also accelerates thrombolysis in animal models. Although the mechanism of this effect is not known, ultrasound does not cause mechanical disruption of clots but rather accelerates enzymatic fibrinolysis. To determine if accelerated fibrinolysis could be related to increased transport of enzyme into clot, we have examined the effect of insonification on the distribution of plasminogen activator between clot and surrounding fluid in vitro. Plasma clots were overlayed with plasma containing 125I-radiolabeled, active-site-blocked recombinant tissue plasminogen activator (rt-PA) and incubated in the presence of 1-MHz ultrasound at 4 W/cm2 or in the absence of ultrasound. The rate of uptake of rt-PA was significantly faster in the presence of ultrasound, reaching 15.5 +/- 1.4% at 4 h compared to 8.2 +/- 1.0% in the absence of ultrasound (p < 0.0001). Similarly, ultrasound increased transport of enzyme from the clot into the surrounding fluid. To determine the effect of ultrasound on the spatial distribution of enzyme, plasma clots were overlayed with plasma containing radiolabeled rt-PA and incubated in the presence or absence of ultrasound. The clots were then snap-frozen, and the radioactivity in serial cryotome sections was determined. Exposure to ultrasound altered the rt-PA distribution, resulting in significantly deeper penetration of rt-PA into the clots. We conclude that exposure to ultrasound increases uptake of rt-PA into clots and also results in deeper penetration. These effects of ultrasound on enzyme transport may contribute to the accelerated fibrinolysis observed in an ultrasound field.
在超声场中体外纤维蛋白溶解加速，并且外部施加的高频超声在动物模型中也加速血栓溶解。尽管这种效应的机制尚不清楚，但超声不会导致血栓的机械破坏，而是加速酶促纤维蛋白溶解。为了确定加速的纤维蛋白溶解是否与酶向血栓中的转运增加有关，我们在体外研究了超声处理对纤溶酶原激活剂在血栓和周围液体之间分布的影响。将血浆凝块覆盖含有125I放射性标记、活性位点被阻断的重组组织纤溶酶原激活剂（rt-PA）的血浆，并在4W/cm2的1MHz超声存在下或无超声的情况下孵育。在有超声的情况下，rt-PA的摄取速率明显更快，4小时时达到15.5±1.4%，而无超声时为8.2±1.0%（p<0.0001）。同样，超声增加了酶从血栓向周围液体的转运。为了确定超声对酶空间分布的影响，将血浆凝块覆盖含有放射性标记rt-PA的血浆，并在有或无超声的情况下孵育。然后将凝块速冻，并测定连续冰冻切片中的放射性。暴露于超声改变了rt-PA的分布，导致rt-PA在血栓中的渗透明显更深。我们得出结论，暴露于超声会增加rt-PA进入血栓的摄取，并且还会导致更深的渗透。超声对酶转运的这些影响可能有助于在超声场中观察到加速的纤维蛋白溶解。
