超声多普勒能增强重组组织型纤溶酶原激活物诱导的自发性脑出血体外血凝块模型中的纤维蛋白溶解。
Doppler sonography enhances rtPA-induced fibrinolysis in an in vitro clot model of spontaneous intracerebral hemorrhages.
机构信息
Department of Neurosurgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
出版信息
PLoS One. 2019 Jan 17;14(1):e0210810. doi: 10.1371/journal.pone.0210810. eCollection 2019.
BACKGROUND
Transcranial Doppler (TCD) was shown to enhance intravascular fibrinolysis by rtPA in ischemic stroke. Studies revealed that catheter-based administration of rtPA induces lysis of intracerebral hemorrhages (ICH). However, it is unknown whether TCD would be suitable to enhance rtPA-induced fibrinolysis in patients with ICH. The aim of this study was to assess the potential of TCD to enhance rtPA-induced fibrinolysis in an in vitro clot system.
METHODS
Reproducible human blood clots of 25 ml were incubated in a water bath at 37°C during treatments. They were weighed before and after 6 different treatments: (I) control (incubation only), (II) rtPA only, (III) one Doppler probe, (IV) two Doppler probes placed vis-à-vis, (V) one probe and rtPA and (VI) two probes and rtPA. To quantify lysis of the blood clots and attenuation of the Doppler through a temporal squama acoustic peak rarefaction pressure (APRP) was measured in the field of the probes. Temperature was assessed to evaluate possible side effects.
RESULTS
Clot weight was reduced in all groups. The control group had the highest relative end weight of 70.2%±7.2% compared to all other groups (p<0,0001). Most efficient lysis was achieved using (VI) 2 probes and rtPA 36.3%±4.4% compared to (II, III, IV) (p<0.0001; p = 0.0002; p = 0.048). APRP was above lysis threshold (535.5±7.2 kPa) using 2 probes even through the temporal squama (731.6±32.5 kPa) (p = 0.0043). There was a maximal temperature elevation of 0.17±0.07°C using both probes.
CONCLUSIONS
TCD significantly enhances rtPA-induced lysis of blood clots, and the effect is amplified by using multiple probes. Our results indicate that bitemporal TCD insonation of hematomas could be a new and safe approach to enhance fibrinolysis of ICH´s treated with intralesional catheter and rtPA.
背景
经颅多普勒（TCD）已被证明可增强缺血性脑卒中患者重组组织型纤溶酶原激活物（rtPA）的血管内纤溶作用。研究表明，导管内给予 rtPA 可诱导颅内出血（ICH）的溶解。然而，目前尚不清楚 TCD 是否适合增强 ICH 患者的 rtPA 诱导的纤溶作用。本研究旨在评估 TCD 在体外血凝块系统中增强 rtPA 诱导的纤溶作用的潜力。
方法
在 37°C 的水浴中孵育 25ml 的可重复的人类血凝块，在 6 种不同的治疗方法中进行处理：（I）对照（仅孵育），（II）仅 rtPA，（III）一个多普勒探头，（IV）两个多普勒探头相对放置，（V）一个探头和 rtPA，以及（VI）两个探头和 rtPA。通过测量探头区域内的 temporal squama 声峰值稀疏压力（APRP）来量化血凝块的溶解和多普勒的衰减。评估温度以评估可能的副作用。
结果
所有组的血凝块重量均减轻。对照组的相对最终重量最高，为 70.2%±7.2%，与所有其他组相比（p<0.0001）。使用（VI）两个探头和 rtPA 时，溶解效率最高，为 36.3%±4.4%，与（II、III、IV）相比（p<0.0001；p = 0.0002；p = 0.048）。即使通过 temporal squama（731.6±32.5kPa），使用两个探头时，APRP 也超过了 535.5±7.2kPa 的溶解阈值（p = 0.0043）。使用两个探头时，温度最大升高 0.17±0.07°C。
结论
TCD 可显著增强 rtPA 诱导的血凝块溶解，并且通过使用多个探头可放大这种作用。我们的结果表明，双颞部 TCD 血肿照射可能是一种新的、安全的方法，可增强接受腔内导管和 rtPA 治疗的 ICH 的纤溶作用。
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