Therapeutic application of contrast ultrasound in ST elevation myocardial infarction: Role in coronary thrombosis and microvascular obstruction.

In the past few decades, cardiac ultrasound has become a widely available, easy-to-use diagnostic tool in many scenarios in acute cardiac care. The introduction of microbubbles extended its diagnostic value. Not long thereafter, several investigators explored the therapeutic potential of contrast ultrasound on thrombus dissolution.

Lymphocytic myocarditis occurs with myocardial infarction and coincides with increased inflammation, hemorrhage and instability in coronary artery atherosclerotic plaques.

Objective: Although lymphocytic myocarditis (LM) clinically can mimic myocardial infarction (MI), they are regarded as distinct clinical entities. However, we observed a high prevalence (32%) of recent MI in patients diagnosed post-mortem with LM. To investigate if LM changes coronary atherosclerotic plaque, we analyzed in autopsied hearts the inflammatory infiltrate and stability in coronary atherosclerotic lesions in patients with LM and/or MI.

CD45 is a more sensitive marker than CD3 to diagnose lymphocytic myocarditis in the endomyocardium.

To diagnose lymphocytic myocarditis (LM), immunohistopathological examination of endomyocardial biopsies (EMBs) is used with a cutoff value of at least 14 leukocytes per mm, composed of CD3- and CD68-positive cells. We hypothesized that a more common leukocyte marker, CD45, instead of CD3 could increase the diagnostic sensitivity. Hearts of mice with acute viral myocarditis (n = 9) and of controls (n = 7) and the EMB sampling area of the left ventricular posterior wall (LVPW) obtained from autopsied hearts of patients diagnosed with LM (n = 18) and controls (n = 6) were stained with anti-CD68, anti-CD3, and anti-CD45.

A comparison in therapeutic efficacy of several time points of intravenous StemBell administration in a rat model of acute myocardial infarction.

Background: Adipose-derived stromal cells (ASCs) are a promising new therapeutic option for patients with acute myocardial infarction (AMI). Previously, we found that ASCs coupled to antibody-targeted microbubbles (StemBells [StBs]) improved cardiac function when administered intravenously 7 days post-AMI in rats. In this study, we compared the efficacy of intravenous StB administration at different administration time points following AMI in rats.

Unexpected High Incidence of Coronary Vasoconstriction in the Reduction of Microvascular Injury Using Sonolysis (ROMIUS) Trial.

High-mechanical-index ultrasound and intravenous microbubbles might prove beneficial in treating microvascular obstruction caused by microthrombi after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). Experiments in animals have revealed that longer-pulse-duration ultrasound is associated with an improvement in microvascular recovery. This trial tested long-pulse-duration, high-mechanical-index ultrasound in STEMI patients.

Colchicine aggravates coxsackievirus B3 infection in mice.

Background: There is a clinical need for immunosuppressive therapy that can treat myocarditis patients in the presence of an active viral infection. In this study we therefore investigated the effects of colchicine, an immunosuppressive drug which has been used successfully as treatment for pericarditis patients, in a mouse model of coxsackievirus B3(CVB3)-induced myocarditis.

Methods: Four groups of C3H mice were included: control mice (n=8), mice infected with CVB3 (1×10(5) PFU, n=10), mice with colchicine administration (2mg/kg i.

Endogenous C1-inhibitor production and expression in the heart after acute myocardial infarction.

Background: Complement activation contributes significantly to inflammation-related damage in the heart after acute myocardial infarction. Knowledge on factors that regulate postinfraction complement activation is incomplete however. In this study, we investigated whether endogenous C1-inhibitor, a well-known inhibitor of complement activation, is expressed in the heart after acute myocardial infarction.

Ultrasound and microbubble-targeted delivery of small interfering RNA into primary endothelial cells is more effective than delivery of plasmid DNA.

Ultrasound and microbubble-targeted delivery (UMTD) is a promising non-viral technique for genetic-based therapy. We found that UMTD of small interfering RNA (siRNA) is more effective than delivery of plasmid DNA (pDNA). UMTD (1 MHz, 0.

Secondary bjerknes forces deform targeted microbubbles.

In this study, we investigated the effect of secondary Bjerknes forces on targeted microbubbles using high-speed optical imaging. We observed that targeted microbubbles attached to an underlying surface and subject to secondary Bjerknes forces deform in the direction of their neighboring bubble, thereby tending toward a prolate shape. The deformation induces an elastic restoring force, causing the bubbles to recoil back to their equilibrium position; typically within 100 μs after low-intensity ultrasound application.

Homocysteine-induced apoptosis in endothelial cells coincides with nuclear NOX2 and peri-nuclear NOX4 activity.

Apoptosis of endothelial cells related to homocysteine (Hcy) has been reported in several studies. In this study, we evaluated whether reactive oxygen species (ROS)-producing signaling pathways contribute to Hcy-induced apoptosis induction, with specific emphasis on NADPH oxidases. Human umbilical vein endothelial cells were incubated with 0.

Intravenous clusterin administration reduces myocardial infarct size in rats.

Background: Clusterin (Apolipoprotein J), a plasma protein with cytoprotective and complement-inhibiting activities, localizes in the infarcted heart during myocardial infarction (MI). Recently, we have shown a protective effect of exogenous clusterin in vitro on ischaemically challenged cardiomyocytes independent of complement. We therefore hypothesized that intravenous clusterin administration would reduce myocardial infarction damage.

Ultrasound and microbubble-induced intra- and intercellular bioeffects in primary endothelial cells.

Recent developments in the field of ultrasound (US) contrast agents have demonstrated that these encapsulated microbubbles can not only be used for diagnostic imaging but may also be employed as therapeutic carriers for localized, targeted drug or gene delivery. The exact mechanisms behind increased uptake of therapeutic compounds by US-exposed microbubbles are still not fully understood. Therefore, we studied the effects of stably oscillating SonoVue microbubbles on relevant parameters of cellular and intercellular permeability, i.

Ultrasound and microbubble-targeted delivery of macromolecules is regulated by induction of endocytosis and pore formation.

Contrast microbubbles in combination with ultrasound (US) are promising vehicles for local drug and gene delivery. However, the exact mechanisms behind intracellular delivery of therapeutic compounds remain to be resolved. We hypothesized that endocytosis and pore formation are involved during US and microbubble targeted delivery (UMTD) of therapeutic compounds.

Low-intensity ultrasound-exposed microbubbles provoke local hyperpolarization of the cell membrane via activation of BK(Ca) channels.

Ultrasound (US) contrast agents have gained wide interest in gene therapy as many researchers reported increased membrane permeability and transfection efficiency by sonoporation in the presence of US contrast agents. We recently demonstrated an increase in cell membrane permeability for Ca2+ in rat cardiomyoblast (H9c2) cells insonified in the presence of microbubbles. In the present study, we specifically investigated whether US-exposed microbubbles have an effect on the cell membrane potential and whether Ca2+-dependent potassium (BK(Ca)) channels are involved.