Regulation of Skeletal Muscle Resistance Arteriolar Tone: Temporal Variability in Vascular Responses.

Introduction: A full understanding of the integration of the mechanisms of vascular tone regulation requires an interrogation of the temporal behavior of arterioles across vasoactive challenges. Building on previous work, the purpose of the present study was to start to interrogate the temporal nature of arteriolar tone regulation with physiological stimuli.

Methods: We determined the response rate of ex vivo proximal and in situ distal resistance arterioles when challenged by one-, two-, and three-parameter combinations of five major physiological stimuli (norepinephrine, intravascular pressure, oxygen, adenosine [metabolism], and intralumenal flow).

Circular RNA Foxo3 in cardiac ischemia-reperfusion injury in heart transplantation: A new regulator and target.

Ischemia-reperfusion (I/R) injury occurring in heart transplantation (HT) remains as a leading cause of transplant heart graft failure. Circular RNAs (circRNAs) play important roles in gene regulation and diseases. However, the impact of circRNAs on I/R injury during HT remains unknown.

An Addition of U0126 Protecting Heart Grafts From Prolonged Cold Ischemia-Reperfusion Injury in Heart Transplantation: A New Preservation Strategy.

Background: Ischemia-reperfusion injury (IRI) is the major cause of primary graft dysfunction in organ transplantation. The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) signaling pathway plays a crucial role in cell physiological and pathological processes including IRI. This study aims to investigate whether inhibition of ERK signaling with U0126 can prevent prolonged cold IRI in heart transplantation.

Antiviral Inflammation during Early Pregnancy Reduces Placental and Fetal Growth Trajectories.

Many viruses are detrimental to pregnancy and negatively affect fetal growth and development. What is not well understood is how virus-induced inflammation impacts fetal-placental growth and developmental trajectories, particularly when inflammation occurs in early pregnancy during nascent placental and embryo development. To address this issue, we simulated a systemic virus exposure in early pregnant rats (gestational day 8.

Supplementing preservation solution with mitochondria-targeted H S donor AP39 protects cardiac grafts from prolonged cold ischemia-reperfusion injury in heart transplantation.

Heart transplant has been accepted as the standard treatment for end-stage heart failure. Because of its susceptibility to ischemia-reperfusion injury, the heart can be preserved for only 4 to 6 hours in cold static preservation solutions. Prolonged ischemia time is adversely associated with primary graft function and long-term survival.

Fortifying Angiogenesis in Ischemic Muscle with FGF9-Loaded Electrospun Poly(Ester Amide) Fibers.

Delivery of angiogenic growth factors lessens ischemia in preclinical models but has demonstrated little benefit in patients with peripheral vascular disease. Augmenting the wrapping of nascent microvessels by mural cells constitutes an alternative strategy to regenerating a functional microvasculature, particularly if integrated with a sustained delivery platform. Herein, electrospun poly(ester amide) (PEA) nanofiber mats are fabricated for delivering a mural cell-targeting factor, fibroblast growth factor 9 (FGF9).

Over-expression of calpastatin attenuates myocardial injury following myocardial infarction by inhibiting endoplasmic reticulum stress.

Background: Ischemic heart injury activates calpains and endoplasmic reticulum (ER) stress in cardiomyocytes. This study investigated whether over-expression of calpastatin, an endogenous calpain inhibitor, protects the heart against myocardial infarction (MI) by inhibiting ER stress.

Methods: Mice over-expressing calpastatin (Tg-CAST) and littermate wild type (WT) mice were divided into four groups: WT-sham, Tg-CAST-sham, WT-MI, and Tg-CAST-MI, respectively.

Compound speckle model detects anti-angiogenic tumor response in preclinical nonlinear contrast-enhanced ultrasonography.

Purpose: This paper proposes a method for analyzing the first-order speckle statistics of nonlinear contrast-enhanced ultrasound images from tumors.

Methods: Contrast signal intensity is modeled as a compound distribution of exponential probability density functions with a gamma weighting function. The gamma probability weighting function serves as an approximation for log-normally distributed flow velocities in a vascular network.

Investigation of Crossbeam Multi-receiver Configurations for Accurate 3-D Vector Doppler Velocity Estimation.

An accurate estimation of low blood velocities whose Doppler shifts span the wall filter cutoff, such as near the wall in recirculation or disturbed flow regions, is important for accurate mapping of velocities to achieve improved estimations of wall shear stress and turbulence, which are known risk factors for atherosclerosis and stroke. This paper presents the comparative benefit of increasing the number of receiver beams above three for an improved estimation of low 3-D velocities. The 3-D crossbeam vector Doppler ultrasound configurations were studied in terms of the number of receiver beams, interbeam angle, and beam selection method (criterion for discriminating between tissue and blood Doppler signals) for a range of velocity orientations, which may prove useful in the design of a future 2-D array for vascular imaging.

Spread-Spectrum Beamforming and Clutter Filtering for Plane-Wave Color Doppler Imaging.

Plane-wave imaging is desirable for its ability to achieve high frame rates, allowing the capture of fast dynamic events and continuous Doppler data. In most implementations of plane-wave imaging, multiple low-resolution images from different plane wave tilt angles are compounded to form a single high-resolution image, thereby reducing the frame rate. Compounding improves the lateral beam profile in the high-resolution image, but it also acts as a low-pass filter in slow time that causes attenuation and aliasing of signals with high Doppler shifts.

Improved Linear Contrast-Enhanced Ultrasound Imaging via Analysis of First-Order Speckle Statistics.

The linear subtraction methods commonly used for preclinical contrast-enhanced imaging are susceptible to registration errors and motion artifacts that lead to reduced contrast-to-tissue ratios. To address this limitation, a new approach to linear contrast-enhanced ultrasound (CEUS) is proposed based on the analysis of the temporal dynamics of the speckle statistics during wash-in of a bolus injection of microbubbles. In the proposed method, the speckle signal is approximated as a mixture of temporally varying random processes, representing the microbubble signal, superimposed onto spatially heterogeneous tissue backscatter in multiple subvolumes within the region of interest.

High Intensity Aerobic Exercise Training Improves Deficits of Cardiovascular Autonomic Function in a Rat Model of Type 1 Diabetes Mellitus with Moderate Hyperglycemia.

Indices of cardiovascular autonomic neuropathy (CAN) in experimental models of Type 1 diabetes mellitus (T1DM) are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV) autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C), sedentary T1DM (D), control exercise (CX), or T1DM exercise (DX).

Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy.

Aims: The mitochondria are important sources of reactive oxygen species (ROS) in the heart. Mitochondrial ROS production has been implicated in the pathogenesis of diabetic cardiomyopathy, suggesting that therapeutic strategies specifically targeting mitochondrial ROS may have benefit in this disease. We investigated the therapeutic effects of mitochondria-targeted antioxidant mito-TEMPO on diabetic cardiomyopathy.

Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice.

Aims/hypothesis: MicroRNAs (miRs) have been suggested as potential therapeutic targets for heart diseases. Inhibition of miR-195 prevents apoptosis in cardiomyocytes stimulated with palmitate and transgenic overexpression of miR-195 induces cardiac hypertrophy and heart failure. We investigated whether silencing of miR-195 reduces diabetic cardiomyopathy in a mouse model of streptozotocin (STZ)-induced type 1 diabetes.

Evidence of bidirectional flow in the sciatic vasa nervorum.

The purpose of this study was to determine whether bidirectional flow exists in the sciatic vasa nervorum. Images obtained using high-frequency color Doppler ultrasound in duplex imaging mode (Vevo 2100) were studied retroactively. In Fig.

The relationship between blood pressure and sciatic nerve blood flow velocity in rats with insulin-treated experimental diabetes.

Peripheral nerve blood flow (NBF) does not autoregulate but, instead, responds passively to changes in mean arterial pressure (MAP). How this relationship is impacted by insulin-treated experimental diabetes (ITED) is unknown. We tested the hypothesis that ITED will reduce NBF across a range of MAP in Sprague Dawley rats.

A method to validate quantitative high-frequency power doppler ultrasound with fluorescence in vivo video microscopy.

Flow quantification with high-frequency (>20 MHz) power Doppler ultrasound can be performed objectively using the wall-filter selection curve (WFSC) method to select the cutoff velocity that yields a best-estimate color pixel density (CPD). An in vivo video microscopy system (IVVM) is combined with high-frequency power Doppler ultrasound to provide a method for validation of CPD measurements based on WFSCs in mouse testicular vessels. The ultrasound and IVVM systems are instrumented so that the mouse remains on the same imaging platform when switching between the two modalities.

Exercise training enhances insulin-stimulated nerve arterial vasodilation in rats with insulin-treated experimental diabetes.

Insulin stimulates nerve arterial vasodilation through a nitric oxide (NO) synthase (NOS) mechanism. Experimental diabetes reduces vasa nervorum NO reactivity. Studies investigating hyperglycemia and nerve arterial vasodilation typically omit insulin treatment and use sedentary rats resulting in severe hyperglycemia.

Glucose-stimulated insulin secretion causes an insulin-dependent nitric oxide-mediated vasodilation in the blood supply of the rat sciatic nerve.

This study tested the hypothesis that acute hyperglycemia reduces sciatic nerve blood flow in Sprague-Dawley rats. Anesthetized rats underwent cannulation of their right jugular vein (for anesthetic/nutrient/drug infusion) and right carotid artery (for continuous blood pressure measurement via pressure transducer). The left sciatic nerve was exposed and nerve blood velocity (NBV) was assessed from an arterial segment lying superficially along the sciatic nerve (Doppler ultrasound, 40 MHz).

Over-expression of calpastatin aggravates cardiotoxicity induced by doxorubicin.

Aims: Doxorubicin causes damage to the heart, which may present as cardiomyopathy. However, the mechanisms by which doxorubicin induces cardiotoxicity remain not fully understood and no effective prevention for doxorubicin cardiomyopathy is available. Calpains, a family of calcium-dependent thiol-proteases, have been implicated in cardiovascular diseases.

3D image-guided robotic needle positioning system for small animal interventions.

Purpose: This paper presents the design of a micro-CT guided small animal robotic needle positioning system. In order to simplify the robotic design and maintain a small targeting error, a novel implementation of the remote center of motion is used in the system. The system has been developed with the objective of achieving a mean targeting error of <200 μm while maintaining a high degree of user friendliness.

Traceable micro-CT scaling accuracy phantom for applications requiring exact measurement of distances or volumes.

Purpose: Volumetric x-ray microcomputed tomography (CT) can be employed in a variety of quantitative research applications such as image-guided interventions or characterization of medical devices. To ensure the highest geometric fidelity of images for these applications, a phantom and image processing algorithm have been developed to calibrate the scaling accuracy of micro-CT scanners to a traceable standard and provide corrections to image voxel sizing.

Methods: The calibration phantom contains six borosilicate beads whose separations have been measured to a traceable standard.

Deficiency of Capn4 gene inhibits nuclear factor-κB (NF-κB) protein signaling/inflammation and reduces remodeling after myocardial infarction.

Calpain has been implicated in acute myocardial injury after myocardial infarction (MI). However, the causal relationship between calpain and post-MI myocardial remodeling has not been fully understood. This study examined whether deletion of Capn4, essential for calpain-1 and calpain-2 activities, reduces myocardial remodeling and dysfunction following MI, and if yes, whether these effects of Capn4 deletion are associated with NF-κB signaling and inflammatory responses in the MI heart.

Y1R control of sciatic nerve blood flow in the Wistar Kyoto rat.

We hypothesized that neuropeptide Y (NPY) exerts vasoconstrictor properties in sciatic nerve blood supply by a Y1 receptor (Y1R) mechanism. Using Doppler ultrasound (40MHz), we measured blood flow velocity through a sciatic nerve supply artery during infusions of NPY and/or Y1R blockade with BIBP3226 in Wistar Kyoto rats before, and following, ganglionic blockade with Hexamethonium (Hex). Following Hex infusion, mean arterial pressure (baseline: 83±18, Hex: 57±3 mm Hg) was reduced.

Improved objective selection of power Doppler wall-filter cut-off velocity for accurate vascular quantification.

The wall-filter selection curve method is proposed to objectively identify a cut-off velocity that minimizes artifacts in power Doppler images. A selection curve, which is constructed by plotting the color pixel density (CPD) as a function of the cut-off velocity, exhibits characteristic intervals hypothesized to include the optimum cut-off velocity. This article presents an improved implementation of the method that automatically detects characteristic intervals in a selection curve and selects an operating point cut-off velocity along a characteristic interval.