Porter Thomas R, Choudhury Songita A, Xie Feng
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Nebraska Medical Center, 982265 Nebraska Medical Center, 68198 Omaha, NE USA.
J Ther Ultrasound. 2016 Jul 15;4:18. doi: 10.1186/s40349-016-0062-y. eCollection 2016.
Diagnostic ultrasound (DUS) pressures have the ability to induce inertial cavitation (IC) of systemically administered microbubbles; this bioeffect has many diagnostic and therapeutic implications in cardiovascular care. Diagnostically, commercially available lipid-encapsulated perfluorocarbons (LEP) can be utilized to improve endocardial and vascular border delineation as well as assess myocardial perfusion. Therapeutically, the liquid jets induced by IC can alter endothelial function and dissolve thrombi within the immediate vicinity of the cavitating microbubbles. The cavitating LEP can also result in the localized release of any bound therapeutic substance at the site of insonation. DUS-induced IC has been tested in pre-clinical studies to determine what effect it has on acute vascular and microvascular thrombosis as well as nitric oxide (NO) release. These pre-clinical studies have consistently shown that DUS-induced IC of LEP is effective in restoring coronary vascular and microvascular flow in acute ST segment elevation myocardial infarction (STEMI), with microvascular flow improving even if upstream large vessel flow has not been achieved. The initial clinical trials examining the efficacy of short pulse duration DUS high mechanical index impulses in patients with STEMI are underway, and preliminary studies have suggested that earlier epicardial vessel recanalization can be achieved prior to arriving in the cardiac catheterization laboratory. DUS high mechanical index impulses have also been effective in pre-clinical studies for targeting DNA delivery that has restored islet cell function in type I diabetes and restored vascular flow in the extremities downstream from a peripheral vascular occlusion. Improvements in this technique will come from three dimensional arrays for therapeutic applications, more automated delivery techniques that can be applied in the field, and use of submicron-sized acoustically activated LEP droplets that may better permeate the clot prior to DUS activation and cavitation. This article will focus on these newer developments for DUS therapeutic applications.
诊断超声（DUS）压力能够引发全身给药的微泡发生惯性空化（IC）；这种生物效应在心血管护理中有许多诊断和治疗意义。在诊断方面，市售的脂质包裹全氟化碳（LEP）可用于改善心内膜和血管边界的勾勒以及评估心肌灌注。在治疗方面，IC引发的液体射流可改变内皮功能并溶解空化微泡紧邻区域内的血栓。空化的LEP还可导致在超声照射部位局部释放任何结合的治疗物质。DUS诱导的IC已在临床前研究中进行测试，以确定其对急性血管和微血管血栓形成以及一氧化氮（NO）释放的影响。这些临床前研究一致表明，DUS诱导的LEP空化在恢复急性ST段抬高型心肌梗死（STEMI）的冠状动脉血管和微血管血流方面是有效的，即使上游大血管血流尚未恢复，微血管血流也会改善。目前正在进行初步临床试验，以检验短脉冲持续时间DUS高机械指数脉冲对STEMI患者的疗效，初步研究表明，在抵达心脏导管实验室之前可以更早地实现心外膜血管再通。DUS高机械指数脉冲在临床前研究中对于靶向DNA递送也很有效，该递送已恢复了I型糖尿病患者的胰岛细胞功能，并恢复了外周血管闭塞下游肢体的血流。该技术的改进将来自用于治疗应用的三维阵列、可在现场应用的更自动化递送技术，以及使用亚微米级声学激活的LEP液滴，其在DUS激活和空化之前可能更好地渗透血栓。本文将重点关注DUS治疗应用的这些新进展。
