Ischemia/Reperfusion Injury Enhances Accumulation of Perfluoropropane Droplets.

Objective: Perfluoropropane droplets (PD) are nanometer-sized particles that can be formulated from commercially available contrast agents. The preferential retention of PDs in diseased microvascular beds can be detected by ultrasound imaging techniques after acoustic activation and offers an opportunity for the detection of such processes as scar formation or inflammation. We hypothesized that in the presence of ischemia/reperfusion (I/R) injury, retention of intravenously injected PDs would be enhanced.

Acoustic Activation Imaging With Intravenous Perfluoropropane Nanodroplets Results in Selective Bioactivation of the Risk Area.

Background: Acoustically activatable perfluoropropane droplets (PD) can be formulated from commercially available microbubble preparations. Diagnostic transthoracic ultrasound frequencies have resulted in acoustic activation (AA) predominately within myocardial infarct zones (IZ).

Objective: We hypothesized that the AA area following acute coronary ischemia/reperfusion (I/R) would selectively enhance the developing scar zone, and target bioeffects specifically to this region.

Fibrin-targeted phase shift microbubbles for the treatment of microvascular obstruction.

Microvascular obstruction (MVO) following percutaneous coronary intervention (PCI) is a common problem associated with adverse clinical outcomes. We are developing a novel treatment, termed sonoreperfusion (SRP), to restore microvascular patency. This entails using ultrasound-targeted microbubble cavitation (UTMC) of intravenously administered gas-filled lipid microbubbles (MBs) to dissolve obstructive microthrombi in the microvasculature.

Ultrasound-Targeted Microbubble Cavitation During Machine Perfusion Reduces Microvascular Thrombi and Graft Injury in a Rat Liver Model of Donation After Circulatory Death.

Background: Ischemic cholangiopathy is a process of bile duct injury that might result from peribiliary vascular plexus (PBP) thrombosis and remains a dreaded complication in liver transplantation from donors after circulatory death (DCD). The aim of this study was to propose a mechanical method of clot destruction to clear microvascular thrombi in DCD livers before transplantation.

Methods: Sonothrombolysis (STL) is a process by which inertial cavitation of circulating microbubbles entering an ultrasound field create a high-energy shockwave at a microbubble-thrombus interface, causing mechanical clot destruction.

Dynamic Behavior of Polymer Microbubbles During Long Ultrasound Tone-Burst Excitation and Its Application for Sonoreperfusion Therapy.

Objective: Ultrasound (US)-targeted microbubble (MB) cavitation (UTMC)-mediated therapies have been found to restore perfusion and enhance drug/gene delivery. Because of the potentially longer circulation time and relative ease of storage and reconstitution of polymer-shelled MBs compared with lipid MBs, we investigated the dynamic behavior of polymer microbubbles and their therapeutic potential for sonoreperfusion (SRP) therapy.

Methods: The fate of polymer MBs during a single long tone-burst exposure (1 MHz, 5 ms) at various acoustic pressures and MB concentrations was recorded via high-speed microscopy and passive cavitation detection (PCD).

Effect of Ultrasound Pulse Length on Sonoreperfusion Therapy.

In recent years, long- and short-pulse ultrasound (US)-targeted microbubble cavitation (UTMC) has been found to increase perfusion in healthy and ischemic skeletal muscle, in pre-clinical animal models of microvascular obstruction and in the myocardium of patients presenting with acute myocardial infarction. There is evidence that the observed microvascular vasodilation is driven by the nitric oxide pathway and purinergic signaling, but the time course of the response and the dependency on US pulse length are not well elucidated. Because our prior data supported that sonoreperfusion efficacy is enhanced by long-pulse US versus short-pulse US, in this study, we sought to compare long-pulse (5000 cycles) and short-pulse (500 × 10 cycles) US at a pressure of 1.

Sex-related differences in clinical outcomes among patients with myocardial infarction with nonobstructive coronary artery disease: A systematic review and meta-analysis.

Background: Among patients who present with acute myocardial infarction (MI), 2-6% are found to have non-obstructive coronary arteries (NOCA). Patients with MINOCA are more commonly women and present at a younger age (51-59 years). The influence of sex on adverse event rates remains unclear.

Lipid nitroalkene nanoparticles for the focal treatment of ischemia reperfusion.

The treatment of microvascular obstruction (MVO) using ultrasound-targeted LNP cavitation (UTC) therapy mechanically relieves the physical obstruction in the microcirculation but does not specifically target the associated inflammatory milieu. Electrophilic fatty acid nitroalkene derivatives (nitro-fatty acids), that display pleiotropic anti-inflammatory signaling and transcriptional regulatory actions, offer strong therapeutic potential but lack a means of rapid targeted delivery. The objective of this study was to develop nitro-fatty acid-containing lipid nanoparticles (LNP) that retain the mechanical efficacy of standard LNP and can rapidly target delivery of a tissue-protective payload that reduces inflammation and improves vascular function following ischemia-reperfusion.

Role of Internal Jugular Venous Ultrasound in suspected or confirmed Heart Failure: A Systematic Review.

Background: Few data are available on the use of internal jugular vein (IJV) ultrasound parameters to assess central venous pressure and clinical outcomes among patients with suspected or confirmed heart failure (HF).

Methods: We performed electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through January 9, 2021, to identify studies evaluating the accuracy and reliability of the IJV ultrasound parameters and exploring its correlation with central venous pressure and clinical outcomes in adult patients with suspected or confirmed acutely decompensated HF. The studies' report quality was assessed by Quality Assessment of Diagnostic Accuracy Studies-2 scale.

Noninvasive sublingual microvascular imaging reveals sex-specific reduction in glycocalyx barrier properties in patients with coronary artery disease.

Background: Risk factors for coronary artery disease (CAD) have been associated with endothelial dysfunction and degradation of the endothelial glycocalyx. This study was designed to compare sublingual microvascular perfusion and glycocalyx barrier properties in CAD patients and controls using noninvasive side stream darkfield imaging.

Methods: Imaging of the sublingual microvasculature was performed in 52 case subjects (CAD confirmed by left heart catheterization) and 63 controls (low Framingham risk score).

Sonoreperfusion therapy for microvascular obstruction: A step toward clinical translation.

Sonoreperfusion therapy is being developed as an intervention for the treatment of microvascular obstruction. We investigated the reperfusion efficacy of two clinical ultrasound systems (a modified Philips EPIQ and a Philips Sonos 7500) in a rat hindlimb microvascular obstruction model. Four ultrasound conditions were tested using 20 min treatments: Sonos single frame, Sonos multi-frame, EPIQ low pressure and EPIQ high pressure.

Ultrasound-Targeted Microbubble Cavitation with Sodium Nitrite Synergistically Enhances Nitric Oxide Production and Microvascular Perfusion.

Microvascular obstruction is a common repercussion of percutaneous coronary intervention for distal microembolization, ischemia-reperfusion injury and inflammation, which increases post-myocardial infarction heart failure and mortality. Ultrasound-targeted microbubble cavitation (UTMC) may resolve microvascular obstruction while activating endothelial nitric oxide synthase (eNOS) and increasing endothelium-derived nitric oxide (NO) bioavailability. Nitrite, a cardioprotective agent, offers an additional source of NO and potential synergy with UTMC.

Bedside Ultrasound Assessment of Jugular Venous Compliance as a Potential Point-of-Care Method to Predict Acute Decompensated Heart Failure 30-Day Readmission.

Background Heart failure is one of the most costly diagnosis-related groups, largely because of hospital readmissions. Objective assessment of volume status to ensure optimization before hospital discharge could significantly reduce readmissions. We previously demonstrated an ultrasound method of quantifying percentage of cross-sectional area ( CSA ) change of the right internal jugular vein with Valsalva that reliably estimates central venous pressure.

The Role of Nitric Oxide during Sonoreperfusion of Microvascular Obstruction.

Microembolization during PCI for acute myocardial infarction can cause microvascular obstruction . MVO severely limits the success of reperfusion therapies, is associated with additional myonecrosis, and is linked to worse prognosis, including death. We have shown, both in and models, that ultrasound and microbubble therapy (termed "sonoreperfusion" or "") is a theranostic approach that relieves MVO and restores perfusion, but the underlying mechanisms remain to be established.

Inertial Cavitation Ultrasound with Microbubbles Improves Reperfusion Efficacy When Combined with Tissue Plasminogen Activator in an In Vitro Model of Microvascular Obstruction.

We have previously reported that long-tone-burst, high-mechanical-index ultrasound (US) and microbubble (MB) therapy can restore perfusion in both in vitro and in vivo models of microvascular obstruction (MVO). Addition of MBs to US has been found to potentiate the efficacy of thrombolytics on large venous thrombi; however, the optimal US parameters for achieving microvascular reperfusion of MVO caused by microthrombi, when combined with tissue plasminogen activator (tPA), are unknown. We sought to elucidate the specific effects of US, with and without tPA, for effective reperfusion of MVO in an in vitro model using both venous and arterial microthrombi.

Sonoreperfusion Therapy Kinetics in Whole Blood Using Ultrasound, Microbubbles and Tissue Plasminogen Activator.

Coronary intervention for myocardial infarction often results in microvascular embolization of thrombus. Sonoreperfusion therapy (SRP) using ultrasound and microbubbles restored perfusion in our in vitro flow model of microvascular obstruction. In this study, we assessed SRP efficacy using whole blood as the perfusate with and without tissue plasminogen activator (tPA).

Effect of Thrombus Composition and Viscosity on Sonoreperfusion Efficacy in a Model of Micro-Vascular Obstruction.

Distal embolization of micro-thrombi during stenting for myocardial infarction causes micro-vascular obstruction (MVO). We have previously shown that sonoreperfusion (SRP), a microbubble (MB)-mediated ultrasound (US) therapy, resolves MVO from venous micro-thrombi in vitro in saline. However, blood is more viscous than saline, and arterial thrombi that embolize during stenting are mechanically distinct from venous clot.

Dynamic Behavior of Microbubbles during Long Ultrasound Tone-Burst Excitation: Mechanistic Insights into Ultrasound-Microbubble Mediated Therapeutics Using High-Speed Imaging and Cavitation Detection.

Ultrasound (US)-microbubble (MB)-mediated therapies have been found to restore perfusion and enhance drug/gene delivery. On the presumption that MBs do not persist during long US exposure under high acoustic pressures, most schemes use short US pulses when a high US pressure is employed. However, we recently observed an enhanced thrombolytic effect using long US pulses at high acoustic pressures.

Treatment of microvascular micro-embolization using microbubbles and long-tone-burst ultrasound: an in vivo study.

Despite epicardial coronary artery reperfusion by percutaneous coronary intervention, distal micro-embolization into the coronary microcirculation limits myocardial salvage during acute myocardial infarction. Thrombolysis using ultrasound and microbubbles (sonothrombolysis) is an approach that induces microbubble oscillations to cause clot disruption and restore perfusion. We sought to determine whether this technique could restore impaired tissue perfusion caused by thrombotic microvascular obstruction.

New insights into mechanisms of sonothrombolysis using ultra-high-speed imaging.

Thrombotic arterial occlusion is the principal etiology for acute cardiovascular syndromes such as stroke, myocardial infarction and unstable angina. Exposing the thrombus to ultrasound and microbubbles facilitates thrombus disruption, making "sonothrombolysis" a potentially powerful therapeutic strategy for thromboembolic diseases. However, optimization of such a strategy, and hence clinical translation, is constrained by an incomplete understanding of mechanisms by which ultrasound-induced microbubble vibrations disrupt blood clots.

New insights into the microvascular mechanisms of drag reducing polymers: effect on the cell-free layer.

Drag-reducing polymers (DRPs) significantly increase blood flow, tissue perfusion, and tissue oxygenation in various animal models. In rectangular channel microfluidic systems, DRPs were found to significantly reduce the near-wall cell-free layer (CFL) as well as modify traffic of red blood cells (RBC) into microchannel branches. In the current study we further investigated the mechanism by which DRP enhances microvascular perfusion.

Volumetric quantification of in vitro sonothrombolysis with microbubbles using high-resolution optical coherence tomography.

Several in vitro and in vivo studies have established accelerated thrombolysis using ultrasound (US) induced microbubble (MB) cavitation. However, the mechanisms underlying MB mediated sonothrombolysis are still not completely elucidated. We performed three-dimensional (3-D) volumetric optical coherence tomography (OCT) imaging before and after the application of contrast US to thrombus.