Sonothrombolysis Using Microfluidically Produced Microbubbles in a Murine Model of Deep Vein Thrombosis.

The need for safe and effective methods to manage deep vein thrombosis (DVT), given the risks associated with anticoagulants and thrombolytic agents, motivated research into innovative approaches to resolve blood clots. In response to this challenge, sonothrombolysis is being explored as a technique that combines microbubbles, ultrasound, and thrombolytic agents to facilitate the aggressive dissolution of thrombi. Prior studies have indicated that relatively large microbubbles accelerate the dissolution process, either in an in vitro or an arterial model. However, sonothrombolysis using large microbubbles must be evaluated in venous thromboembolism diseases, where blood flow velocity is not comparable. In this study, the efficacy of sonothrombolysis was validated in a murine model of pre-existing DVT. During therapy, microfluidically produced microbubbles of 18 µm diameter and recombinant tissue plasminogen activator (rt-PA) were administered through a tail vein catheter for 30 min, while ultrasound was applied to the abdominal region of the mice. Three-dimensional ultrasound scans were performed before and after therapy for quantification. The residual volume of the thrombi was 20% in animals post sonothrombolysis versus 52% without therapy ( p = 0.012 < 0.05 ), indicating a significant reduction in DVT volume. Histological analysis of tissue sections confirmed a reduction in DVT volume post-therapy. Therefore, large microbubbles generated from a microfluidic device show promise in ultrasound-assisted therapy to address concerns related to venous thromboembolism.

A Quantitative Method for the Evaluation of Deep Vein Thrombosis in a Murine Model Using Three-Dimensional Ultrasound Imaging.

Deep vein thrombosis (DVT) is a life-threatening condition that can lead to its sequelae pulmonary embolism (PE) or post-thrombotic syndrome (PTS). Murine models of DVT are frequently used in early-stage disease research and to assess potential therapies. This creates the need for the reliable and easy quantification of blood clots. In this paper, we present a novel high-frequency 3D ultrasound approach for the quantitative evaluation of the volume of DVT in an in vitro model and an in vivo murine model. The proposed method involves the use of a high-resolution ultrasound acquisition system and semiautomatic segmentation of the clot. The measured 3D volume of blood clots was validated to be correlated with in vitro blood clot weights with an R2 of 0.89. Additionally, the method was confirmed with an R2 of 0.91 in the in vivo mouse model with a cylindrical volume from macroscopic measurement. We anticipate that the proposed method will be useful in pharmacological or therapeutic studies in murine models of DVT.

Targeted PERK inhibition with biomimetic nanoclusters confers preventative and interventional benefits to elastase-induced abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is a progressive aortic dilatation, causing ∼80% mortality upon rupture. Currently, there is no approved drug therapy for AAA. Surgical repairs are invasive and risky and thus not recommended to patients with small AAAs which, however, account for ∼90% of the newly diagnosed cases. It is therefore a compelling unmet clinical need to discover effective non-invasive strategies to prevent or slow down AAA progression. We contend that the first AAA drug therapy will only arise through discoveries of both effective drug targets and innovative delivery methods. There is substantial evidence that degenerative smooth muscle cells (SMCs) orchestrate AAA pathogenesis and progression. In this study, we made an exciting finding that PERK, the endoplasmic reticulum (ER) stress Protein Kinase R-like ER Kinase, is a potent driver of SMC degeneration and hence a potential therapeutic target. Indeed, local knockdown of PERK in elastase-challenged aorta significantly attenuated AAA lesions in vivo. In parallel, we also conceived a biomimetic nanocluster (NC) design uniquely tailored to AAA-targeting drug delivery. This NC demonstrated excellent AAA homing via a platelet-derived biomembrane coating; and when loaded with a selective PERK inhibitor (PERKi, GSK2656157), the NC therapy conferred remarkable benefits in both preventing aneurysm development and halting the progression of pre-existing aneurysmal lesions in two distinct rodent models of AAA. In summary, our current study not only establishes a new intervention target for mitigating SMC degeneration and aneurysmal pathogenesis, but also provides a powerful tool to facilitate the development of effective drug therapy of AAA.

Dietary therapy in abdominal aortic aneurysm - Insights from clinical and experimental studies.

Abdominal aortic aneurysm (AAA) is a prevalent vascular disease with high mortality rates upon rupture. Despite its prevalence in elderly populations, there remain limited treatment options; invasive surgical repair, while risky, is the only therapeutic intervention with proven clinical benefits. Dietary factors have long been suggested to be closely associated with AAA risks, and dietary therapies recently emerged as promising avenues to achieve non-invasive management of a wide spectrum of diseases. However, the role of dietary therapies in AAA remains elusive. In this article, we will summarize the recent clinical and pre-clinical efforts in understanding the therapeutic and mechanistic implications of various dietary patterns and therapeutic approaches in AAA.

Paravalvular leak closure of acute mitral valve ring dehiscence during mitral valve-in-ring procedure.

The replacement of surgically corrected mitral valves, also known as percutaneous transcatheter repair, is a relatively young field. Even though these procedures are usually successful, they can present significant intraoperative or postoperative challenges. To our knowledge, we present the first case of acute focal dehiscence of mitral ring repair during the mitral valve-in-ring procedure.