UNASSIGNED: It is not known whether the transition from obesity and severe obesity, as 2 different metabolic disease entities, affect flow-mediated and, thus, endothelium-dependent epicardial vasodilation.
UNASSIGNED: The purpose of this study was to investigate the effect of obesity and severe obesity on flow-mediated epicardial vasomotion with positron emission tomography/computed tomography-determined longitudinal decrease in myocardial blood flow (MBF) from the base-to-apex direction of the left ventricle or gradient.
UNASSIGNED: 13N-ammonia positron emission tomography/computed tomography evaluated global MBF during pharmacologically induced hyperemia and at rest for assessment of coronary microvascular function. In addition, the Δ longitudinal MBF gradient (hyperemia minus rest) was determined. Patients were then grouped according to the body mass index (BMI) into normal weight (NW) (BMI 20.0-24.9 kg/m2, n = 27), overweight (OW) (BMI 25.0-29.9 kg/m2, n = 29), obesity (OB) (BMI 30.0-39.9 kg/m2, n = 53), and severe obesity (morbid obesity: BMI ≥40 kg/m2, n = 43).
UNASSIGNED: Compared to NW, left ventricular Δ longitudinal MBF gradient progressively declined in OW and OB (0.04 ± 0.09 mL/g/min vs -0.11 ± 0.14 mL/g/min and -0.15 ± 0.11 mL/g/min; P ≤ 0.001, respectively) but not significantly in SOB (-0.01 ± 0.11 mL/g/min, P = 0.066). Regadenoson-induced global hyperemic MBF was lower in OB than in NW (1.88 ± 0.40 mL/g/min vs 2.35 ± 0.32 mL/g/min; P ≤ 0.001), while comparable between NW and SOB (2.35 ± 0.32 mL/g/min vs 2.26 ± 0.40 mL/g/min; P = 0.302). The BMI of the study population was associated with the Δ longitudinal MBF gradient in a U-turn fashion (r = 0.362, standard error of the estimate = 0.124; P < 0.001).
UNASSIGNED: Increased body weight associates with abnormalities in coronary circulatory function that advances from an impairment flow-mediated, epicardial vasodilation in overweight and obesity to coronary microvascular dysfunction in obesity, not observed in severe obesity. The U-turn of flow-mediated epicardial vasomotion outlines obesity and severe obesity to affect epicardial endothelial function differently.

Background: Erectile dysfunction (ED) most often has vascular etiology and usually is the earliest symptom of vascular dysfunction. The aim of this study was to evaluate vascular dysfunction with the use of the Flow-Mediated Skin Fluorescence (FMSF) technique in men with and without ED. Methods: Included were 39 men (median age 53) with ED and 40 men (median age 41.5) without ED. Medical interview, physical examination, and anthropometrical measurements were performed for all participants. The serum total testosterone, LH, and SHBG determinations were performed in patients with ED, and the Free Testosterone Index (FTI) was calculated. The FMSF technique was used to measure the microcirculatory oscillations at the baseline and to determine the flowmotion (FM) and vasomotion (VM) parameters. The Normoxia Oscillatory Index (NOI) was calculated, which represents the contribution of the endothelial (ENDO) and neurogenic (NEURO) oscillations relative to all oscillations detected at low-frequency intervals (<0.15 Hz): NOI = (ENDO + NEURO)/(ENDO + NEURO + VM). Results: In men with ED were found significantly lower FM and VM parameters, but the NOI was significantly higher in comparison to men without ED. VM and FM correlated significantly positively with erectile function, orgasmic function, and general sexual satisfaction in the whole group and the FTI in the ED group. The thresholds of 53.5 FM (AUC = 0.7) and 8.4 VM (AUC = 0.7) were predictive values for discriminating men with ED. Conclusions: It was shown that the FMSF diagnostic technique may be helpful in the early diagnosis of microcirculation dysfunction due to impaired vasomotion caused by decreased testosterone activity.

Bioresorbable stents represent a revolutionary treatment for coronary artery disease. Such a device offers the prospect for complete naturalization of artery lumen after strut resorption and restoration of vasomotion while curtailing the duration of dual anti-platelet therapy. The prototype bioresorbable scaffold (BRS-ABSORB GT1) demonstrated good feasibility and safety in the initial studies compared to metallic drug eluting stent but later fell out of favor due to multiple report of stent thrombosis and target lesion failure. Unpredictable resorption of struts turned out to be one of the \"Achilles heel\" of the BRS and stent strut were still visible in vessel on optical coherence tomography (OCT) at 3 years. We report a case of differential resorption of two ABSORB BRS implanted simultaneously in the same patient by the same operator. Follow up coronary angiogram revealed only minimal plaques on right coronary artery (RCA) and left anterior descending artery (LAD). The BRS were identified on cine-angiogram by their radio-opaque markers at both ends. The OCT run in LAD artery revealed \"ghost remnants\" of BRS struts in LAD, whereas the RCA BRS had completely healed with minimal \"ghost\" struts. The ghost remnants of BRS resembled the original \"Check box\" appearance on OCT during the index implantation.

The presence of global synchronization of vasomotion induced by oscillating visual stimuli was identified in the mouse brain. Endogenous autofluorescence was used and the vessel \'shadow\' was quantified to evaluate the magnitude of the frequency-locked vasomotion. This method allows vasomotion to be easily quantified in non-transgenic wild-type mice using either the wide-field macro-zoom microscopy or the deep-brain fiber photometry methods. Vertical stripes horizontally oscillating at a low temporal frequency (0.25 Hz) were presented to the awake mouse, and oscillatory vasomotion locked to the temporal frequency of the visual stimulation was induced not only in the primary visual cortex but across a wide surface area of the cortex and the cerebellum. The visually induced vasomotion adapted to a wide range of stimulation parameters. Repeated trials of the visual stimulus presentations resulted in the plastic entrainment of vasomotion. Horizontally oscillating visual stimulus is known to induce horizontal optokinetic response (HOKR). The amplitude of the eye movement is known to increase with repeated training sessions, and the flocculus region of the cerebellum is known to be essential for this learning to occur. Here, we show a strong correlation between the average HOKR performance gain and the vasomotion entrainment magnitude in the cerebellar flocculus. Therefore, the plasticity of vasomotion and neuronal circuits appeared to occur in parallel. Efficient energy delivery by the entrained vasomotion may contribute to meeting the energy demand for increased coordinated neuronal activity and the subsequent neuronal circuit reorganization.

Pancreatic islets are endocrine organs that depend on their microvasculature to function. Along with endothelial cells, pericytes comprise the islet microvascular network. These mural cells are crucial for microvascular stability and function, but it is not known if/how they are affected during the development of type 1 diabetes (T1D). Here, we investigate islet pericyte density, phenotype, and function using living pancreas slices from donors without diabetes, donors with a single T1D-associated autoantibody (GADA+), and recent onset T1D cases. Our data show that islet pericyte and capillary responses to vasoactive stimuli are impaired early on in T1D. Microvascular dysfunction is associated with a switch in the phenotype of islet pericytes toward myofibroblasts. Using publicly available RNA sequencing (RNA-seq) data, we further found that transcriptional alterations related to endothelin-1 signaling and vascular and extracellular matrix (ECM) remodeling are hallmarks of single autoantibody (Aab)+ donor pancreata. Our data show that microvascular dysfunction is present at early stages of islet autoimmunity.

Vascular factors are known to be early and important players in Alzheimer\'s disease (AD) development, however the role of the ε4 allele of the Apolipoprotein (APOE) gene (a risk factor for developing AD) remains unclear. APOE4 genotype is associated with early and severe neocortical vascular deficits in anaesthetised mice, but in humans, vascular and cognitive dysfunction are focused on the hippocampal formation and appear later. How APOE4 might interact with the vasculature to confer AD risk during the preclinical phase represents a gap in existing knowledge. To avoid potential confounds of anaesthesia and to explore regions most relevant for human disease, we studied the visual cortex and hippocampus of awake APOE3 and APOE4-TR mice using 2-photon microscopy of neurons and blood vessels. We found mild vascular deficits: vascular density and functional hyperaemia were unaffected in APOE4 mice, and neuronal or vascular function did not decrease up to late middle-age. Instead, vascular responsiveness was lower, arteriole vasomotion was reduced and neuronal calcium signals during visual stimulation were increased. This suggests that, alone, APOE4 expression is not catastrophic but stably alters neurovascular physiology. We suggest this state makes APOE4 carriers more sensitive to subsequent insults such as injury or beta amyloid accumulation.

BACKGROUND: Post-occlusive reactive hyperemia (PORH) test with signal spectral analysis coupled provides potential indicators for the assessment of microvascular functions.
OBJECTIVE: The objective of this study is to investigate the variations of skin blood flow and temperature spectra in the PORH test. Furthermore, to quantify the oscillation amplitude response to occlusion within different frequency ranges.
METHODS: Ten healthy volunteers participated in the PORH test and their hand skin temperature and blood flow images were captured by infrared thermography (IRT) and laser speckle contrast imaging (LSCI) system, respectively. Extracted signals from selected areas were then transformed into the time-frequency space by continuous wavelet transform for cross-correlation analysis and oscillation amplitude response comparisons.
RESULTS: The LSCI and IRT signals extracted from fingertips showed stronger hyperemia response and larger oscillation amplitude compared with other areas, and their spectral cross-correlations decreased with frequency. According to statistical analysis, their oscillation amplitudes in the PORH stage were obviously larger than the baseline stage within endothelial, neurogenic, and myogenic frequency ranges (p < 0.05), and their quantitative indicators of oscillation amplitude response had high linear correlations within endothelial and neurogenic frequency ranges.
CONCLUSIONS: Comparisons of IRT and LSCI techniques in recording the reaction to the PORH test were made in both temporal and spectral domains. The larger oscillation amplitudes suggested enhanced endothelial, neurogenic, and myogenic activities in the PORH test. We hope this study is also significant for investigations of response to the PORH test by other non-invasive techniques.

UNASSIGNED: Small animal fMRI is an essential part of translational research in the cognitive neurosciences. Due to small dimensions and animal physiology preclinical fMRI is prone to artifacts that may lead to misinterpretation of the data. To reach unbiased translational conclusions, it is, therefore, crucial to identify potential sources of experimental noise and to develop correction methods for contributions that cannot be avoided such as physiological noise. Aim of this study was to assess origin and prevalence of hemodynamic oscillations (HDO) in preclinical fMRI in rat, as well as their impact on data analysis.
UNASSIGNED: Following the development of algorithms for HDO detection and suppression, HDO prevalence in fMRI measurements was investigated for different anesthetic regimens, comprising isoflurane and medetomidine, and for both gradient echo and spin echo fMRI sequences. In addition to assessing the effect of vasodilation on HDO, it was studied if HDO have a direct neuronal correlate using local field potential (LFP) recordings. Finally, the impact of HDO on analysis of fMRI data was assessed, studying both the impact on calculation of activation maps as well as the impact on brain network analysis. Overall, 303 fMRI measurements and 32 LFP recordings were performed in 71 rats.
UNASSIGNED: In total, 62% of the fMRI measurements showed HDO with a frequency of (0.20 ± 0.02) Hz. This frequent occurrence indicated that HDO cannot be generally neglected in fMRI experiments. Using the developed algorithms, HDO were detected with a specificity of 95%, and removed efficiently from the signal time courses. HDO occurred brain-wide under vasoconstrictive conditions in both small and large blood vessels. Vasodilation immediately interrupted HDO, which, however, returned within 1 h under vasoconstrictive conditions. No direct neuronal correlate of HDO was observed in LFP recordings. HDO significantly impacted analysis of fMRI data, leading to altered cluster sizes and F-values for activated voxels, as well as altered brain networks, when comparing data with and without HDO.
UNASSIGNED: We therefore conclude that HDO are caused by vasomotion under certain anesthetic conditions and should be corrected during fMRI data analysis to avoid bias.

Sensory stimulation evokes a local, vasodilation-mediated blood flow increase to the activated brain region, which is referred to as functional hyperemia. Spontaneous vasomotion is a change in arteriolar diameter that occurs without sensory stimulation, at low frequency (∼0.1 Hz). These vessel diameter changes are a driving force for perivascular soluble waste clearance, the failure of which has been implicated in neurodegenerative disease. Stimulus-evoked vascular reactivity is known to propagate along penetrating arterioles to pial arterioles, but it is unclear whether spontaneous vasomotion propagates similarly. We therefore imaged both stimulus-evoked and spontaneous changes in pial arteriole diameter in awake, head-fixed mice with 2-photon microscopy. By cross-correlating different regions of interest (ROIs) along the length of imaged arterioles, we assessed vasomotion propagation. We found that both during rest and during visual stimulation, one-third of the arterioles showed significant propagation (i.e., a wave), with a median (interquartile range) wave speed of 405 (323) µm/s at rest and 345 (177) µm/s during stimulation. In a second group of mice, with GCaMP expression in their vascular smooth muscle cells, we also found spontaneous propagation of calcium signaling along pial arterioles. In summary, we demonstrate that spontaneous vasomotion propagates along pial arterioles like stimulus-evoked vascular reactivity.

The regulation of oxygen in brain tissue is one of the most important fundamental questions in neuroscience and medicine. The brain is a metabolically demanding organ, and its health directly depends on maintaining oxygen concentrations within a relatively narrow range that is both sufficiently high to prevent hypoxia, and low enough to restrict the overproduction of oxygen species. Neurovascular interactions, which are responsible for oxygen delivery, consist of neuronal and glial components. GABAergic interneurons play a particularly important role in neurovascular interactions. The involvement of interneurons extends beyond the perspective of inhibition, which prevents excessive neuronal activity and oxygen consumption, and includes direct modulation of the microvasculature depending upon their sub-type. Namely, nitric oxide synthase-expressing (NOS), vasoactive intestinal peptide-expressing (VIP), and somatostatin-expressing (SST) interneurons have shown modulatory effects on microvessels. VIP interneurons are known to elicit vasodilation, SST interneurons typically cause vasoconstriction, and NOS interneurons have to propensity to induce both effects. Given the importance and heterogeneity of interneurons in regulating local brain tissue oxygen concentrations, we review their differing functions and developmental trajectories. Importantly, VIP and SST interneurons display key developmental milestones in adolescence, while NOS interneurons mature much earlier. The implications of these findings point to different periods of critical development of the interneuron-mediated oxygen regulatory systems. Such that interference with normal maturation processes early in development may effect NOS interneuron neurovascular interactions to a greater degree, while insults later in development may be more targeted toward VIP- and SST-mediated mechanisms of oxygen regulation.