Microbubbles improve sonothrombolysis in vitro and decrease hemorrhage in vivo in a rabbit stroke model.
Microbubbles improve sonothrombolysis in vitro and decrease hemorrhage in vivo in a rabbit stroke model.
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DOI：
10.1097/rli.0b013e318200757a
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发表时间：
2011-03
影响因子：
6.7
通讯作者：
Culp WC
中科院分区：
文献类型：
--
作者：
Brown AT;Flores R;Hamilton E;Roberson PK;Borrelli MJ;Culp WC
组织纤溶酶原激活剂（tPA）是急性缺血性中风的溶栓治疗标准，但脑出血（ICH）仍然是一种常见且具有破坏性的并发症。我们研究了使用超声 (US) 和微泡 (MB) 技术来减少所需的 tPA 剂量并减少 ICH。将新鲜血凝块（3-5 小时）在体外暴露于 tPA（0.02 或 0.1 mg/mL）加上脉冲 1 MHz US（0.1 W/cm2），有或没有 1.12 × 108/mL MB（Definity 或白蛋白/葡萄糖 MB [adMB]）。测量血块质量损失以量化血栓溶解。新西兰白兔 (n = 120) 在 3 至 5 小时内接受一个通过血管造影输送到颈内动脉的血块。所有患者均接受 1 MHz US (0.8 W/cm2) 经皮脉冲 60 分钟，并静脉注射 tPA (0.1–0.9 mg/kg)，加或不加 Definity MB (0.16 mL/mg/kg)。杀死动物后，24小时后取出大脑进行组织学检查。在体外，无论是否使用 tPA，MB（Definity 或 adMB）均显着增加超声诱导的血栓丢失（P < 0.0001）。与 Definity 相比，在 0 和 0.02 mg/mL 浓度下，adMB 的 tPA 血栓损失更大（P ≤ 0.05）。使用MB，tPA剂量减少了5倍，效果良好。在体内，与对照组相比，Definity MB 和 tPA 组的梗塞体积较小，分别为 P < 0.0183 和 P < 0.0003。与对照组相比，Definity MB+tPA 减少了梗塞体积 (P < 0.0001)，与无 MB 相比，中风以外的 ICH 发生率显着降低 (P = 0.005)。然而，Definity MB 与 tPA 中的梗塞体积没有差异，P = 0.19。将 tPA 和 MB 结合使用极低剂量甚至无剂量的 tPA 即可有效减少血块，并且减少了兔子急性中风的梗塞体积和 ICH。 MB 降低 tPA 需求的能力可能会降低人类中风治疗中的出血率。
Tissue plasminogen activator (tPA) is the thrombolytic standard of care for acute ischemic stroke, but intracerebral hemorrhage (ICH) remains a common and devastating complication. We investigated using ultrasound (US) and microbubble (MB) techniques to reduce required tPA doses and to decrease ICH. Fresh blood clots (3–5 hours) were exposed in vitro to tPA (0.02 or 0.1 mg/mL) plus pulsed 1 MHz US (0.1 W/cm2), with or without 1.12 × 108/mL MBs (Definity or albumin/dextrose MBs [adMB]). Clot mass loss was measured to quantify thrombolysis. New Zealand white rabbits (n = 120) received one 3- to 5-hour clot angiographically delivered into the internal carotid artery. All had transcutaneous pulsed 1 MHz US (0.8 W/cm2) for 60 minutes and intravenous tPA (0.1– 0.9 mg/kg) with or without Definity MBs (0.16 mL/mg/kg). After killing the animals, the brains were removed for histology 24 hours later. In vitro, MBs (Definity or adMB) increased US-induced clot loss significantly, with or without tPA (P < 0.0001). At 0 and 0.02 mg/mL, tPA clot loss was greater with adMBs compared with Definity (P ≤ 0.05). With MB, the tPA dose was reduced 5-fold with good efficacy. In vivo, both Definity MB and tPA groups had less infarct volume compared with controls at P < 0.0183 and P < 0.0003, respectively. Definity MB+tPA reduces infarct volume compared with controls (P < 0.0001), and ICH incidence outside of strokes was significantly lower (P = 0.005) compared with no MB. However, infarct volume in Definity MB versus tPA was not different at P = 0.19. Combining tPAand MB yielded effective loss of clot with very low dose or even no dose tPA, and infarct volumes and ICH were reduced in acute strokes in rabbits. The ability of MBs to reduce tPA requirements may lead to lower rates of hemorrhage in human stroke treatment.