Kashyap A, Blinc A, Marder V J, Penney D P, Francis C W
Department of Medicine, University of Rochester School of Medicine & Dentistry, New York 14642.
Thromb Res. 1994 Dec 1;76(5):475-85. doi: 10.1016/0049-3848(95)90179-j.
High frequency ultrasound has been previously shown to accelerate fibrinolysis in vitro at intensities that are potentially applicable for noninvasive administration clinically. To extend these findings in vivo, we have investigated the effects of ultrasound on fibrinolysis induced by streptokinase in a rabbit model of small vessel injury. Full thickness puncture wounds were made in rabbit ears with a scalpel blade. The rabbits were rested for 2-3 hours after cessation of bleeding to allow maturation of hemostatic plugs. Saline or streptokinase was then infused intravenously, and ultrasound was applied to some lesions at 1 MHz with a 50% duty cycle at 1 W/cm2 net intensity. Ear lesions in rabbits treated with saline showed no bleeding after 30 minutes whether they were exposed to ultrasound or not. Streptokinase alone induced bleeding after 19.7 +/- 5.5 minutes. Application of ultrasound significantly reduced the time to bleeding in streptokinase treated rabbits to 7.5 +/- 3.9 minutes (p < .002). The times to bleeding with "sham" ultrasound (18.8 +/- 5.6 minutes) and heating of the ear (18.0 +/- 5.6 minutes) during streptokinase administration were not significantly different compared to streptokinase alone. Histologic examination revealed that application of ultrasound resulted in a mild increase in interstitial edema and accumulation of polymorphonuclear leukocytes but did not cause vascular or other tissue damage. We conclude that the noninvasive, percutaneous application of ultrasound significantly accelerated streptokinase-induced fibrinolysis in this rabbit model of small vessel injury.
高频超声先前已被证明，在临床上可能适用于无创给药的强度下，可在体外加速纤维蛋白溶解。为了在体内扩展这些发现，我们研究了超声对兔小血管损伤模型中链激酶诱导的纤维蛋白溶解的影响。用手术刀刀片在兔耳上制作全层穿刺伤口。出血停止后，让兔子休息2 - 3小时，以使止血栓成熟。然后静脉注射生理盐水或链激酶，并以1W/cm²的净强度、50%的占空比，对一些损伤部位施加1MHz的超声。用生理盐水治疗的兔子，无论是否接受超声照射，其耳部损伤在30分钟后均无出血。单独使用链激酶在19.7±5.5分钟后诱导出血。超声的应用显著缩短了链激酶治疗的兔子的出血时间，至7.5±3.9分钟（p < 0.002）。在链激酶给药期间，“假”超声（18.8±5.6分钟）和耳部加热（18.0±5.6分钟）后的出血时间与单独使用链激酶相比，无显著差异。组织学检查显示，超声的应用导致间质水肿轻度增加和多形核白细胞积聚，但未引起血管或其他组织损伤。我们得出结论，在这个兔小血管损伤模型中，无创、经皮应用超声显著加速了链激酶诱导的纤维蛋白溶解。
