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Purpose: To quantitatively assess choriocapillaris (CC) flow deficits in eyes with diabetic retinopathy (DR) using swept-source optical coherence tomography angiography (SS-OCTA). Methods: Diabetic subjects with different stages of DR and age-matched healthy subjects were recruited and imaged with SS-OCTA. The en face CC blood flow images were generated using previously published and validated algorithms. The percentage of CC flow deficits (FD%) and the mean CC flow deficit size were calculated in a 5-mm-diameter circle centered on the fovea from the 6×6-mm scans. Results: Forty-five diabetic subjects and 27 control subjects were included in the study. The CC FD% in diabetic eyes was on average 1.4-fold greater than in control eyes (12.34±4.14% vs 8.82±2.61%, P < 0.001). The mean CC FD size in diabetic eyes was on average 1.4-fold larger than in control eyes (2151.3± 650.8μm2 vs 1574.4±255.0 μm2, P < 0.001). No significant difference in CC FD% or mean CC FD size was observed between eyes with nonproliferative DR and eyes with proliferative DR (P = 1.000 and P = 1.000, respectively). Conclusions: CC perfusion in DR can be objectively and quantitatively assessed with FD% and FD size. In the macular region, both CC FD% and CC FD size are increased in eyes with DR. SS-OCTA provides new insights for the investigations of CC perfusion status in diabetes in vivo. [ABSTRACT FROM AUTHOR]

We have reported previously that renal hemodynamic abnormalities exist in the prediabetic stage of type II diabetic rats. At this prediabetic stage these rats have hyperinsulinemia, insulin resistance and metabolic syndrome. It is well known that insulin resistance is frequently associated with renal abnormalities, but the mechanism underlying this association has remained speculative. Although insulin is known to modify renal hemodynamics, little is known about the roles of insulin receptor substrates (IRS1, IRS2) in the renal actions of insulin. To address this issue, the effects of insulin on renal function and renal hemodynamics were investigated in C57BL/6 (WT: wild type), insulin receptor substrate 1- knockout (IRS1–/–), and IRS2-knockout (IRS2–/–) mice. IRS2–/–mice had elevated glucose level as expected. 24-h urine collections and serum creatinine revealed that creatinine clearance did not significantly differ between these groups. Albuminuria was found in IRS1–/–and IRS2–/–groups. We examined the effects on the IRS during the administration of Losartan, which is widely used for diabetic nephropathy. After the administration of Losartan the IRS displayed improved renal hemodynamics. Moreover, the subjects were also given Pioglitazone, which improves insulin resistance. Losartan significantly reduced albuminuria in both groups. Pioglitazone also showed similar results. We assessed the autoregulatory responses of the total renal blood flow (RBF), the superficial (SBF) and the deep renal cortical blood flow (DBF) with stepwise reductions of renal perfusion pressure (RPP), which was induced by a manual clamp on the abdominal aorta. During the clamp induced reductions of the RPP by 10 to 20mm HG, RBF, SBF and the DBF fell significantly more in the IRS1 and IRS2 than in the WT mice. Furthermore micropuncture studies showded that compared to the WT tubuloglomerular feedback (TGF) responses of the stop flow pressure (Psf) were reduced in both the IRS1 -/- and IRS2 -/-. The results of the IRS1 and IRS2 mice displayed the pressence of hemodynamic abnormalities. Losartan and Pioglitazone have shown the potential to improve these abnormalities. In conclusion the results indicate that IRS plays a major role in the stimulation of renal functions and renal hemodynamics in type type II diabetes. [ABSTRACT FROM AUTHOR]

Non-invasive, repeated interrogation of the same wound is necessary to understand the tissue repair continuum. In this work, we sought to test the significance of non-invasive high-frequency high-resolution ultrasound technology for such interrogation. High-frequency high-resolution ultrasound imaging was employed to investigate wound healing under fetal and adult conditions. Quantitative tissue cellularity and elastic strain was obtained for visualization of unresolved inflammation using Vevo strain software. Hemodynamic properties of the blood flow in the artery supplying the wound-site were studied using color Doppler flow imaging. Non-invasive monitoring of fetal and adult wound healing provided unprecedented biomechanical and functional insight. Fetal wounds showed highly accelerated closure with transient perturbation of wound tissue cellularity. Fetal hemodynamics was unique in that sharp fall in arterial pulse pressure (APP) which was rapidly restored within 48h post-wounding. In adults, APP transiently increased post-wounding before returning to the pre-wounding levels by d10 post-wounding. The pattern of change in the elasticity of wound-edge tissue of diabetics was strikingly different. Severe strain acquired during the early inflammatory phase persisted with a slower recovery of elasticity compared to that of the non-diabetic group. Wound bed of adult diabetic mice (db/db) showed persistent hypercellularity compared to littermate controls (db/+) indicative of prolonged inflammation. Normal skin strain of db/+ and db/db were asynchronous. In db/db, severe strain acquired during the early inflammatory phase persisted with a slower recovery of elasticity compared to that of non-diabetics. This study showcases a versatile clinically relevant imaging platform suitable for real-time analyses of functional wound healing. [ABSTRACT FROM AUTHOR]

Endothelial cells (ECs) are subjected to physical forces such as shear stress (SS) induced by blood flow that leads to significant changes in morphology, physiology and gene expression. The abnormal mechanical forces applied in the cardiovascular system can influence the development of conditions and diseases such as thrombosis, hypertension and atherosclerosis. This study investigated the expression of glycosaminoglycans (GAGs), proteoglycans and extracellular matrix molecules in ECs exposed to normal and altered SS. ECs were exposed to SS of 12 dyn/cm2 (artery physiological condition) and 4 dyn/cm2 (artery pathological condition). Subsequently, ECs were subjected to immunofluorescence, qPCR, GAG biosynthesis analyses and cell-based assays. SS induced changes in ECs morphology. There were other pathological consequences of altered SS, including inhibited adhesion, stimulation of migration and capillary-like tube formation, as well as increases of GAG synthesis. We observed higher expression of syndecan-4, perlecan, decorin, fibronectin and collagen III α1 and growth factors, including VEGF-A and TGFβ-1. ECs exposed to SS displayed extracellular matrix remodeling as well as expression of cell-matrix and cell-cell interaction molecules. This study contributes to the understanding of how vascular biology is affected by mechanical forces and how these molecules can be affected in cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Objectives: Evaluation of intestinal perfusion remains subjective and depends on the surgeon´s individual experience. Intraoperative quality assessment of tissue perfusion with indocyanine green (ICG) fluorescence using a near-infrared camera system has been described in different ways and for different indications. The aim of the present study was to evaluate fluorescent imaging (FI) in the quantitative assessment of intestinal perfusion in a gastric tube model in pigs and to compare the results to results obtained with florescent microspheres (FM), the gold standard for tissue perfusion. Methods: Seven pigs (56.0±3.0 kg), both males and females, underwent gastric tube formation after transection and ligation of the gastric arteries, except the right gastroepiploic artery, to avoid collateral blood flow. After baseline assessment (T0), hypotension (T1) was induced by propofol (Karampinis et al 2017) (< 60 mmHg). Then, propofol was paused to obtain normotension (T2, Mean arterial pressure (MAP) 60–90 mmHg). Finally, hypertension (T3, MAP>90 mmHg) was induced by norepinephrine. Measurements were performed in three regions of interest (ROIs) under standardized conditions: the fundus (D1), corpus (D2), and prepyloric area (D3). Hemodynamic parameters and transit-time flow measurement (TTFM) in the right gastroepiploic artery were continuously assessed. FI, FM and the partial pressure of tissue oxygen (TpO2) were quantified in each ROI. Results: The study protocol could successfully be performed during stable hemodynamics. Flow in the gastroepiploic artery measured by transit time flow measurement (TTFM) was related to hemodynamic changes between the measurements, indicating improved blood flow with increasing MAP. The distal part of the gastric tube (D1) showed significantly (p<0.05) impaired perfusion compared to the proximal parts D3 and D2 using FM. ICG-FI also showed the highest values in D3 and the lowest values in D1 at all hemodynamic levels (T1-T3; p<0,05). Conclusion: Visual and quantitative assessment of gastric tube perfusion is feasible in an experimental setting using ICG-FI. This might be a promising tool for intraoperative assessment during visceral surgery in the future. [ABSTRACT FROM AUTHOR]

Background: The quantitative measurement of current perception threshold (CPT) has been used as a method to assess the function of nerve fibers in neuropathy diseases. The aim of this study was to assess the test-retest reliability measuring CPT using the circular pin electrodes for assessing the function of cutaneous thin nerve fibers. Methods: CPT measurement was repeated on two separate days with at least one-week interval in 55 volunteers. Superficial blood flow (SBF) and skin temperature (ST) were measured on the skin in an around area concentric to the circular pin electrodes after the process of finding CPTs. The coefficient of variation (CV) and intra-class correlation coefficient (ICC) were calculated. The correlation between each two of CPT, SBF increment and ST increment was analyzed. Results: No significant differences were found for CPT, SBF and ST between two sessions. SBF was found to be significantly increased after the process of finding CPT. CPT values of males were found to be higher than females. SBF increment was found to be positively correlated with ST increment. The ICC values for CPT, SBF and ST were 0.595, 0.852 and 0.728, respectively. The CV values for CPT, SBF and ST were 25.53%, 12.59% and 1.94%, respectively. Conclusions: The reliability of CPT measurement using circular pin electrodes is fair, and need consistence of measurements in longitudinal studies. [ABSTRACT FROM AUTHOR]

Heterotopic and orthotopic ovarian tissue autotransplantation techniques, currently used in humans, will become promising alternative methods for fertility preservation in domestic and wild animals. Thus, this study describes for the first time the efficiency of a heterotopic ovarian tissue autotransplantation technique in a large livestock species (i.e., horses) after ovarian fragments were exposed or not to a cooling process (4°C/24 h) and/or VEGF before grafting. Ovarian fragments were collected in vivo via an ultrasound-guided biopsy pick-up method and surgically autografted in a subcutaneous site in both sides of the neck in each mare. The blood flow perfusion at the transplantation site was monitored at days 2, 4, 6, and 7 post-grafting using color-Doppler ultrasonography. Ovarian grafts were recovered 7 days post-transplantation and subjected to histological analyses. The exposure of the ovarian fragments to VEGF before grafting was not beneficial to the quality of the tissue; however, the cooling process of the fragments reduced the acute hyperemia post-grafting. Cooled grafts compared with non-cooled grafts contained similar values for normal and developing preantral follicles, vessel density, and stromal cell apoptosis; lower collagen type III fibers and follicular density; and higher stromal cell density, AgNOR, and collagen type I fibers. In conclusion, VEGF exposure before autotransplantation did not improve the quality of grafted tissues. However, cooling ovarian tissue for at least 24 h before grafting can be beneficial because satisfactory rates of follicle survival and development, stromal cell survival and proliferation, as well as vessel density, were obtained. [ABSTRACT FROM AUTHOR]

Optical coherence tomography angiography (OCTA) is a novel, non-invasive imaging tool used to detect vascular flow. The absence of a flow signal in OCTA in polyps revealed by indocyanine green angiography (ICGA) in patients with polypoidal choroidal vasculopathy (PCV) may indicate slow or compromised filling of blood flow from choroidal vessels. Naïve patients with PCV treated with intravitreal injections of aflibercept (IVI-A) were enrolled in this study to validate the hypothesis that baseline flow may affect the outcome of polyp regression in ICGA. The flow signal of polyps in OCTA was detected by manual segmentation in the corresponding location by ICGA. Polyps were defined as high-flow if both OCTA and ICGA showed positive findings, and low-flow if OCTA showed a negative flow signal in 3 consecutive horizontal scans at the polyp area shown in ICGA. A total of 24 polyps were identified in 13 PCV patients at baseline. Of these 24 polyps, 22 (91.7%) were high-flow and 2 (8.3%) were low-flow. After 3 monthly IVI-A, all low-flow polyps had complete regression in ICGA. Among 17 (77%) high-flow polyps at baseline that had regression after treatment, 10 (58.8%) became low-flow, while 5 (22.7%) persistent polyps remained high-flow. Flow signal of polyps as detected by OCTA could be a predictive factor for treatment response in patients with PCV. Monitoring changes in flow signal after treatment is clinically relevant. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) is an emerging tool for diagnosis and treatment monitoring of chronic thromboembolic pulmonary hypertension (CTEPH). The current study aims to identify central pulmonary arterial hemodynamic parameters that reflect clinical, cardiac and pulmonary changes after PEA. 31 CTEPH patients, who underwent PEA and received pre- and postoperative MRI, were analyzed retrospectively. Central pulmonary arterial blood flow, lung perfusion and right heart function data were derived from MRI. Mean pulmonary arterial pressure (mPAP) and 5-month follow-up six-minute walk-distance (6MWD) were assessed. After PEA, mPAP decreased significantly and patients achieved a higher 6MWD. Central pulmonary arterial blood flow velocities, pulmonary blood flow (PBF) and right ventricular function increased significantly. Two-dimensional (2D) phase-contrast (PC) MRI-derived average mean velocity, maximum mean velocity and deceleration volume changes after PEA correlated with changes of 6MWD and right heart ejection fraction (RVEF). Deceleration volume is a novel 2D PC MRI parameter showing further correlation with PBF changes. In conclusion, 2D PC MRI-derived main pulmonary hemodynamic changes reflect changes of RVEF, PBF and 5-month follow-up 6MWD and may be used for future CTEPH patient monitoring after PEA. [ABSTRACT FROM AUTHOR]

Exercise exerts a beneficial effect on the major pathological and clinical symptoms associated with Alzheimer's disease in humans and mouse models of the disease. While numerous mechanisms for such benefits from exercise have been proposed, a clear understanding of the causal links remains elusive. Recent studies also suggest that cerebral blood flow in the brain of both Alzheimer's patients and mouse models of the disease is decreased and that the cognitive symptoms can be improved when blood flow is restored. We therefore hypothesized that the mitigating effect of exercise on the development and progression of Alzheimer's disease may be mediated through an increase in the otherwise reduced brain blood flow. To test this idea, we performed a pilot study to examine the impact of three months of voluntary wheel running in a small cohort of ~1-year-old APP/PS1 mice on short-term memory function, brain inflammation, amyloid deposition, and baseline cerebral blood flow. Our findings that exercise led to a trend toward improved spatial short-term memory, reduced brain inflammation, markedly increased neurogenesis in the dentate gyrus, and a reduction in hippocampal amyloid-beta deposits are consistent with other reports on the impact of exercise on the progression of Alzheimer's related symptoms in mouse models. Notably, we did not observe any impact of wheel running on overall baseline blood flow nor on the incidence of non-flowing capillaries, a mechanism we recently identified as one contributing factor to cerebral blood flow deficits in mouse models of Alzheimer's disease. Overall, our findings add to the emerging picture of differential effects of exercise on cognition and blood flow in Alzheimer's disease pathology by showing that capillary stalling is not decreased following exercise. [ABSTRACT FROM AUTHOR]

Arterial growth and remodeling at the tissue level is driven by mechanobiological processes at cellular and sub-cellular levels. Although it is widely accepted that cells seek to promote tissue homeostasis in response to biochemical and biomechanical cues—such as increased wall stress in hypertension—the ways by which these cues translate into tissue maintenance, adaptation, or maladaptation are far from understood. In this paper, we present a logic-based computational model for cell signaling within the arterial wall, aiming to predict changes in extracellular matrix turnover and cell phenotype in response to pressure-induced wall stress, flow-induced wall shear stress, and exogenous sources of angiotensin II, with particular interest in mouse models of hypertension. We simulate a number of experiments from the literature at both the cell and tissue level, involving single or combined inputs, and achieve high qualitative agreement in most cases. Additionally, we demonstrate the utility of this modeling approach for simulating alterations (in this case knockdowns) of individual nodes within the signaling network. Continued modeling of cellular signaling will enable improved mechanistic understanding of arterial growth and remodeling in health and disease, and will be crucial when considering potential pharmacological interventions. Author summary: Biological soft tissues are characterized by continuous production and removal of material, which endows them with a remarkable ability to adapt to changes in their biochemical and biomechanical environments. For arteries, mechanical stimuli result primarily from changes in blood pressure or flow, and biochemical changes are induced by multiple factors, including pharmacological intervention. In order to understand how arterial properties are maintained in health, or how they adapt or fail to adapt in disease, we must understand better how these diverse stimuli affect material turnover. Extracellular matrix is tightly regulated by mechano-sensing and mechano-regulation, and therefore cell signaling, thus we present a computational model of relevant signaling pathways within the vascular wall, with the aim of predicting changes in wall composition and function in response to three main inputs: pressure-induced wall stress, flow-induced wall shear stress, and exogenous angiotensin II. We obtain qualitative agreement with a range of experimental studies from the literature, and provide illustrative examples demonstrating how such models can be used to further our understanding of arterial remodeling. [ABSTRACT FROM AUTHOR]

Background: It is controversial to evaluate the function of hydronephrotic kidneys by renal dynamic imaging (RDI). Our aim was to study the features of renal dynamic imaging (RDI) at different stages after unilateral ureteral obstruction (UUO) and to investigate a method that could be reasonably used to evaluate renal function and predict renal functional recoverability. Methods: We made UUO models using fifteen adult New Zealand white rabbits and systematically observed the changes in kidney morphology, blood flow, radiotracer distribution and function by RDI. We then compared the differences in terms of imaging features between different periods and analyzed the relationship between blood flow and function in obstructed kidneys. Results: 1) Obstructed kidneys gradually became larger than preoperative kidneys and contralateral kidneys (P<0.05) and reached their peak size between days 42 and 56, after which they gradually got smaller in size. 2)The correlation between the blood perfusion of the obstructed kidney and the obstruction duration (r = 0.125, P = 0.045) was very weak. In the initial period of obstruction, the perfusion of the obstructed kidney significantly decreased, followed by a sharp rebound in later days, and then the perfusion declined again. The peak in blood perfusion was on day 7. 3) The uptake rate of the obstructed kidney drastically decreased in the early stage and became lower than that of the contralateral kidney and the kidney before the operation (P<0.05), after which uptake increased gradually; the peak was on day 28. After that, uptake gradually decreased. 4) The grading of the radiotracer distribution in obstructed kidneys was positively correlated with the obstruction duration (r = 0.975, P = 0.000), and a uniform renal distribution was an early feature of obstruction. 5) The blood perfusion of the obstructed kidney and its functioning frequently increased or decreased simultaneously, but sometimes there was also a mismatch. The peak of renal blood perfusion recovery occurred prior to the peak of renal function recovery. Conclusion: In different periods of severe UUO, the imaged features of obstructed kidneys were different. These features are beneficial for determining the degree of hydronephrosis and renal function and predicting renal functional recoverability. [ABSTRACT FROM AUTHOR]

The host innate immune system has developed elegant processes for the detection and clearance of invasive fungal pathogens. These strategies may also aid in the spread of pathogens in vivo, although technical limitations have previously hindered our ability to view the host innate immune and endothelial cells to probe their roles in spreading disease. Here, we have leveraged zebrafish larvae as a model to view the interactions of these host processes with the fungal pathogen Candida albicans in vivo. We examined three potential host-mediated mechanisms of fungal spread: movement inside phagocytes in a "Trojan Horse" mechanism, inflammation-assisted spread, and endothelial barrier passage. Utilizing both chemical and genetic tools, we systematically tested the loss of neutrophils and macrophages and the loss of blood flow on yeast cell spread. Both neutrophils and macrophages respond to yeast-locked and wild type C. albicans in our model and time-lapse imaging revealed that macrophages can support yeast spread in a "Trojan Horse" mechanism. Surprisingly, loss of immune cells or inflammation does not alter dissemination dynamics. On the other hand, when blood flow is blocked, yeast can cross into blood vessels but they are limited in how far they travel. Blockade of both phagocytes and circulation reduces rates of dissemination and significantly limits the distance of fungal spread from the infection site. Together, this data suggests a redundant two-step process whereby (1) yeast cross the endothelium inside phagocytes or via direct uptake, and then (2) they utilize blood flow or phagocytes to travel to distant sites. Author summary: Although Candida albicans is the most common cause of fungal bloodstream infection, we know little about how it spreads from one tissue to another. Host processes often inadvertently assist pathogens that can hijack immune cells or induce endothelial endocytosis. Here we have used transparent zebrafish to visualize how specific host cells and processes contribute to yeast spread in vivo. We find that Candida is a sophisticated pathogen that uses redundant strategies to disseminate in the host: it can either use host immune cells or cross into the circulatory system and use blood flow. These data suggest that both of these mechanisms must be targeted to limit Candida dissemination during infection. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a gaseous signaling molecule that plays an important role in neurovascular coupling. NO produced by neurons diffuses into the smooth muscle surrounding cerebral arterioles, driving vasodilation. However, the rate of NO degradation in hemoglobin is orders of magnitude higher than in brain tissue, though how this might impact NO signaling dynamics is not completely understood. We used simulations to investigate how the spatial and temporal patterns of NO generation and degradation impacted dilation of a penetrating arteriole in cortex. We found that the spatial location of NO production and the size of the vessel both played an important role in determining its responsiveness to NO. The much higher rate of NO degradation and scavenging of NO in the blood relative to the tissue drove emergent vascular dynamics. Large vasodilation events could be followed by post-stimulus constrictions driven by the increased degradation of NO by the blood, and vasomotion-like 0.1–0.3 Hz oscillations could also be generated. We found that these dynamics could be enhanced by elevation of free hemoglobin in the plasma, which occurs in diseases such as malaria and sickle cell anemia, or following blood transfusions. Finally, we show that changes in blood flow during hypoxia or hyperoxia could be explained by altered NO degradation in the parenchyma. Our simulations suggest that many common vascular dynamics may be emergent phenomena generated by NO degradation by the blood or parenchyma. Author summary: Nitric oxide (NO) generated by neurons during states of increased neural activity dilates arteries, increasing local cerebral blood flow. Scavenging of nitric oxide is much more rapid in the blood than in the tissue, but how the dynamics of NO production and degradation affect the coupling between neural activity and vasodilation is not understood. Here we used computer simulations to model how nitric oxide produced by neurons leads to changes in arteriole size. We find that because nitric oxide is removed from the brain by the blood, changes in arteriole size or blood composition play a role in shaping neurally evoked changes in cerebral blood flow. As the arteriole dilates and supplies more blood, nitric oxide is removed by the blood at a faster rate and this interaction is able to reproduce many commonly observed arteriole dynamics. These dynamics can also be affected by pathologies where blood cells break down, providing a potential link between the state of the blood and blood flow dynamics in the brain. [ABSTRACT FROM AUTHOR]

Cortical spreading depolarization (SD) waves negatively affect neuronal survival and outcome after ischemic stroke. We here aimed to investigate the effects of vagus nerve stimulation (VNS) on SDs in a rat model of focal ischemia. To this end, we delivered non-invasive VNS (nVNS) or invasive VNS (iVNS) during permanent middle cerebral artery occlusion (MCAO), and found that both interventions significantly reduced the frequency of SDs in the cortical peri-infarct area compared to sham VNS, without affecting relative blood flow changes, blood pressure, heart rate or breathing rate. In separate groups of rats subjected to transient MCAO, we found that cortical stroke volume was reduced 72 h after transient MCAO, whereas stroke volume in the basal ganglia remained unchanged. In rats treated with nVNS, motor outcome was improved 2 days after transient MCAO, but was similar to sham VNS animals 3 days after ischemia. We postulate that VNS may be a safe and efficient intervention to reduce the clinical burden of SD waves in stroke and other conditions. [ABSTRACT FROM AUTHOR]

Hemorrhagic shock is one of the leading causes of mortality and morbidity in pediatric trauma. Current treatment based on volume resuscitation is associated to adverse effects, and it has been proposed that vasopressors may be used in the pharmacological management of trauma. Terlipressin has demonstrated its usefulness in other pediatric critical care scenarios and its long half-life allows its use as a bolus in an outpatient critical settings. The aim of this study was to analyze whether the addition of a dose of terlipressin to the initial volume expansion produces an improvement in hemodynamic and cerebral perfusion at early stages of hemorrhagic shock in an infant animal model. We conducted an experimental randomized animal study with 1-month old pigs. After 30 minutes of hypotension (mean arterial blood pressure [MAP]<45 mmHg) induced by the withdrawal of blood over 30 min, animals were randomized to receive either normal saline (NS) 30 mL/kg (n = 8) or a bolus of 20 mcg/kg of terlipressin plus 30 mL/kg of normal saline (TP) (n = 8). Global hemodynamic and cerebral monitoring parameters, brain damage markers and histology samples were compared. After controlled bleeding, significant decreases were observed in MAP, cardiac index (CI), central venous pressure, global end-diastolic volume index (GEDI), left cardiac output index, SvO2, intracranial pressure, carotid blood flow, bispectral index (BIS), cerebral perfusion pressure (CPP) and increases in systemic vascular resistance index, heart rate and lactate. After treatment, MAP, GEDI, CI, CPP and BIS remained significantly higher in the TP group. The addition of a dose of terlipressin to initial fluid resuscitation was associated with hemodynamic improvement, intracranial pressure maintenance and better cerebral perfusion, which would mean protection from ischemic injury. Brain monitoring through BIS was able to detect changes caused by hemorrhagic shock and treatment. [ABSTRACT FROM AUTHOR]

Objective: To examine whether the cardiac, renal and uterine physiological hemodynamic changes during gestation are altered in rats with an early and prolonged exposure to a high fat diet (HFD). Methods: Arterial pressure and cardiac, renal, uterine and radial arteries hemodynamic changes during gestation were examined in adult SD rats exposed to normal (13%) (n = 8) or high (60%) (n = 8) fat diets from weaning. Plethysmography, high-resolution high-frequency ultrasonography and clearance of an inulin analog were used to evaluate the arterial pressure and hemodynamic changes before and at days 7, 14 and 19 of gestation. Results: Arterial pressure was higher (P<0.05) in rats with high than in those with normal (NFD) fat diet before pregnancy (123 ±3 and 110 ±3 mmHg, respectively) and only decreased at day 14 of gestation in rats with NFD (98±4 mmHg, P<0.05). A significant increment in stroke volume (42 ±10%) and cardiac output (51 ±12%) was found at day 19 of pregnancy in rats with NFD. The changes in stroke volume and cardiac output were similar in rats with NFD and HFD. When compared to the values obtained before pregnancy, a transitory elevation in renal blood flow was found at day 14 of pregnancy in both groups. However, glomerular filtration rate only increased (P<0.05) in rats with NFD at days 14 (20 ±7%) and 19 (27 ±8%) of gestation. The significant elevations of mean velocity, and velocity time integral throughout gestation in radial (127 ±26% and 111 ±23%, respectively) and uterine (91 ±16% and 111 ±25%, respectively) arteries of rats with NFD were not found in rats with an early and prolonged HFD. Summary: This study reports novel findings showing that the early and prolonged exposure to a HFD leads to a significant impairment in the renal, uterine and radial arteries hemodynamic changes associated to gestation. [ABSTRACT FROM AUTHOR]

Objective: Cardiovascular disease is a leading cause of death worldwide. Obesity-related metabolic disorders including dyslipidemia cause impaired collateralization under ischemic conditions, thereby resulting in exacerbated cardiovascular dysfunction. Pemafibrate is a novel selective PPARα modulator, which has been reported to improve atherogenic dyslipidemia, in particular, hypertriglyceridemia and low HDL-cholesterol. Here, we investigated whether pemafibrate modulates the revascularization process in a mouse model of hindlimb ischemia. Methods and results: Male wild-type (WT) mice were randomly assigned to two groups, normal diet or pemafibrate admixture diet from the ages of 6 weeks. After 4 weeks, mice were subjected to unilateral hindlimb surgery to remove the left femoral artery and vein. Pemafibrate treatment enhanced blood flow recovery and capillary formation in ischemic limbs of mice, which was accompanied by enhanced phosphorylation of endothelial nitric oxide synthase (eNOS). Treatment of cultured endothelial cells with pemafibrate resulted in increased network formation and migratory activity, which were blocked by pretreatment with the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Pemafibrate treatment also increased plasma levels of the PPARα-regulated gene, fibroblast growth factor (FGF) 21 in WT mice. Systemic administration of adenoviral vectors expressing FGF21 (Ad-FGF21) to WT mice enhanced blood flow recovery, capillary density and eNOS phosphorylation in ischemic limbs. Treatment of cultured endothelial cells with FGF21 protein led to increases in endothelial cell network formation and migration, which were canceled by pretreatment with L-NAME. Furthermore, administration of pemafibrate or Ad-FGF21 had no effects on blood flow in ischemic limbs in eNOS-deficient mice. Conclusion: These data suggest that pemafibrate can promote revascularization in response to ischemia, at least in part, through direct and FGF21-mediated modulation of endothelial cell function. Thus, pemafibrate could be a potentially beneficial drug for ischemic vascular disease. [ABSTRACT FROM AUTHOR]

Background: Sustained inflation (SI) during chest compression (CC = CC+SI) has been recently shown as an alternative method during cardiopulmonary resuscitation in neonates. However, the optimal peak inflation pressure (PIP) of SI during CC+SI to improve ROSC and hemodynamic recovery is unknown. Objective: To examine if different PIPs of SI during CC+SI will improve ROSC and hemodynamic recovery in severely asphyxiated piglets. Methods: Twenty-nine newborn piglets (1–3 days old) were anesthetized, intubated, instrumented and exposed to 30-min normocapnic hypoxia followed by asphyxia. Piglets were randomized into four groups: CC+SI with a PIP of 10 cmH2O (CC+SI_PIP_10, n = 8), a PIP of 20 cmH2O (CC+SI_PIP_20, n = 8), a PIP of 30 cmH2O (CC+SI_PIP_30, n = 8), and a sham-operated control group (n = 5). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. Results: Baseline parameters were similar between all groups. There was no difference in asphyxiation (duration and degree) between intervention groups. PIP correlated positively with tidal volume (VT) and inversely with exhaled CO2 during cardiopulmonary resuscitation. Time to ROSC and rate of ROSC were similar between piglets resuscitated with CC+SI_PIP_10, CC+SI_PIP_20, and CC+SI_PIP_30 cmH2O: median (IQR) 75 (63–193) sec, 94 (78–210) sec, and 85 (70–90) sec; 5/8 (63%), 7/8 (88%), and 3/8 (38%) (p = 0.56 and p = 0.12, respectively). All piglets that achieved ROSC survived to four hours post-resuscitation. Piglets resuscitated with CC+SI_PIP_30 cmH2O exhibited increased concentrations of pro-inflammatory cytokines interleukin-1β and tumour necrosis factor-α in the frontoparietal cerebral cortex (both p<0.05 vs. sham-operated controls). Conclusion: In asphyxiated term newborn piglets resuscitated by CC+SI, the use of different PIPs resulted in similar time to ROSC, but PIP at 30 cmH2O showed a larger VT delivery, lower exhaled CO2 and increased tissue inflammatory markers in the brain. [ABSTRACT FROM AUTHOR]

The cerebral vasculature has a complex and hierarchical network, ranging from vessels of a few millimeters to superficial cortical vessels with diameters of a few hundred micrometers, and to the microvasculature (arteriole/venule) and capillary beds in the cortex. In standard imaging techniques, it is difficult to segment all vessels in the network, especially in the case of the human brain. This study proposes a hybrid modeling approach that determines these networks by explicitly segmenting the large vessels from medical images and employing a novel vascular generation algorithm. The framework enables vasculatures to be generated at coarse and fine scales for individual arteries and veins with vascular subregions, following the personalized anatomy of the brain and macroscale vasculatures. In this study, the vascular structures of superficial cortical (pial) vessels before they penetrate the cortex are modeled as a mesoscale vasculature. The validity of the present approach is demonstrated through comparisons with partially observed data from existing measurements of the vessel distributions on the brain surface, pathway fractal features, and vascular territories of the major cerebral arteries. Additionally, this validation provides some biological insights: (i) vascular pathways may form to ensure a reasonable supply of blood to the local surface area; (ii) fractal features of vascular pathways are not sensitive to overall and local brain geometries; and (iii) whole pathways connecting the upstream and downstream entire-scale cerebral circulation are highly dependent on the local curvature of the cerebral sulci. Author summary: Cerebral autoregulation in the complex vascular networks of the brain is an amazing achievement. We believe that numerical analysis of the cerebral blood circulation using an anatomically precise vascular model provides a powerful tool for evaluating the direct relationships between local- and global-scale blood flows. However, there is a lack of information about the overall vascular pathways in the human brain, preventing a monolithic model of the human cerebrovasculature from being established. This paper presents a multiscale model of human cerebrovasculature based on a hybrid approach that uses image-based geometries and a newly developed mathematical algorithm. One important argument of this paper is the validity of the cerebrovasculature represented in the model, which reflects anatomical features of major cerebral vasculatures and brain shape, and has strong similarities with available data for human superficial cortical vessels. Investigations of the reconstructed model allow us to derive some biological insights and associated hypotheses for the cerebral vasculature. The authors believe the present cerebrovascular model can be applied to numerical simulations of the entire-scale cerebral blood flow. [ABSTRACT FROM AUTHOR]

We aimed to examine aneurysm hemodynamics with intra-saccular pressure measurement, and compare the effects of coiling, stenting and stent-assisted coiling in proximal segments of intracranial circulation. A cohort of 45 patients underwent elective endovascular coil embolization (with or without stent) for intracranial aneurysm at our department. Arterial pressure transducer was used for all measurements. It was attached to proximal end of the microcatheter. Measurements were taken in the parent artery before and after embolization, at the aneurysm dome before embolization, after stent implantation, and after embolization. Stent-assisted coiling was performed with 4 different stents: LVIS and LVIS Jr (Microvention, Tustin, CA, USA), Leo (Balt, Montmorency, France), Barrel VRD (Medtronic/ Covidien, Irvine, CA, USA). Presence of the stent showed significant reverse correlation with intra-aneurysmal pressure–both systolic and diastolic—after its implantation (r = -0.70 and r = -0.75, respectively), which was further supported by correlations with stent cell size–r = 0.72 and r = 0.71, respectively (P<0.05). Stent implantation resulted in significant decrease in diastolic intra-aneurysmal pressure (p = 0.046). Systolic or mean intra-aneurysmal pressure did not differ significantly. Embolization did not significantly change the intra-aneurysmal pressure in matched pairs, regardless of the use of stent (p>0.05). In conclusion, low-profile braided stents show a potential to divert blood flow, there was significant decrease in diastolic pressure after stent placement. Flow-diverting properties were related to stent porosity. Coiling does not significantly change the intra-aneurysmal pressure, regardless of packing density. [ABSTRACT FROM AUTHOR]

The decline in circulatory function with aging may be alleviated by a combination of gingival massage (physical stimulation) and mechanical cleaning. Several studies have reported the systemic effect of physical stimulation on various parts of the body, including its therapeutic effect on pain in the neck and shoulders that becomes evident with age, and improvement in blood circulation. In contrast, few studies have reported on the changes in gingival microcirculation induced by gingival massage, while no previous study has evaluated the effect of gingival microcirculation on age-related changes in the hemodynamics of the oral cavity. This study aimed to investigate how gingival massage affects age-related changes in gingival microcirculation. Male Wistar rats (7-week, 6-month and 1-year old) were prepared for a gingival massage group and a control group. Mechanical stimulation was applied on the maxillary molar gingiva for 5 seconds twice a week for 4 weeks. Subsequently, gingival reactive hyperemia was measured using a laser Doppler flowmeter. In addition, morphological analyses were also performed by hematoxylin and eosin and Indian ink staining and a vascular resin cast model. Base Flow, maximum response (Peak), and time required for the maximum response to halve (T1/2) were reduced in 1-year-old rats compared with the other age groups. In the mechanical stimulated group, T1/2 was increased in 7-week, 6-month, and 1-year-old rats, and total blood flow (Mass) was increased in 6-month and 1-year-old rats. In addition, clear blood vessel networks and loop-like revascularization were only observed in the mechanical stimulated group. Changes in age-related decline in gingival microcirculatory function and vascular construction were reported in this study, and the results suggested that gingival massage activates both the functional and morphological aspects of gingival microcirculation and may be effective for maintaining oral health. [ABSTRACT FROM AUTHOR]

Objective: There are controversial opinions on anticoagulation for continuous venovenous hemofiltration (CVVH) in patients with liver failure (LF) and increased bleeding risk. Therefore, we conducted a retrospective study to evaluate the efficacy and safety of regional citrate anticoagulation (RCA) versus no-anticoagulation for CVVH in these patients. Methods: The included patients were divided into RCA and no-anticoagulation group according to the CVVH anticoagulation strategy they accepted for CVVH. Filter lifespan, bleeding, citrate accumulation, catheter occlusion, and totCa/ionCa ratio were evaluated as outcomes. Results: In the original cohort, the filter lifespan of the RCA group (41 patients, 79 filters) was significantly longer than the no-anticoagulation group (62 patients, 162 filters) (> 72 hours vs 39.5 hours (IQR 31.2–47.8), P = 0.002). The adjusted results demonstrated that RCA could significantly reduce the risk of filter failure (HR = 0.459, 95%CI 0.26–0.82, P = 0.008). Four episodes of totCa/ionCa > 2.5 were observed in the RCA group and continuously accepted RCA-CVVH after the reduction of citrate dose and blood flow. No obvious citrate accumulation was observed in these patients. In the matched cohort, the filter lifespan of the RCA group was significantly longer than the no-anticoagulation group (P = 0.013) as well. No significant difference in the episodes of totCa/ionCa > 2.5 was observed between the two matched groups (P = 0.074). Both in the original cohort and the matched cohort, the bleeding, acidosis, alkalosis, and catheter occlusion incidences were not significantly different between the two groups. Conclusions: In LF patients with increased bleeding risk who underwent CVVH, RCA could prolong the filter lifespan and be safely used with careful blood gas monitoring and citrate dose adjusting. Further prospective, randomized, control studies are warranted to obtain robust evidences. [ABSTRACT FROM AUTHOR]

Mechanical interactions between flowing and coagulated blood (thrombus) are crucial in dictating the deformation and remodeling of a thrombus after its formation in hemostasis. We propose a fully-Eulerian, three-dimensional, phase-field model of thrombus that is calibrated with existing in vitro experimental data. This phase-field model considers spatial variations in permeability and material properties within a single unified mathematical framework derived from an energy perspective, thereby allowing us to study effects of thrombus microstructure and properties on its deformation and possible release of emboli under different hemodynamic conditions. Moreover, we combine this proposed thrombus model with a particle-based model which simulates the initiation of the thrombus. The volume fraction of a thrombus obtained from the particle simulation is mapped to an input variable in the proposed phase-field thrombus model. The present work is thus the first computational study to integrate the initiation of a thrombus through platelet aggregation with its subsequent viscoelastic responses to various shear flows. This framework can be informed by clinical data and potentially be used to predict the risk of diverse thromboembolic events under physiological and pathological conditions. Author summary: Thromboembolism is associated with detachment of small thrombus pieces from the bulk in the blood vessel. These detached pieces, also known as emboli, travel through the blood flow and may block other vessels downstream, e.g., they may plug the deep veins of the leg, groin or arm, leading to venous thromboembolism (VTE). VTE is a significant cause of morbidity and mortality and it affects more than 900,000 people in the United States and result in approximately 100,000 deaths every year. Mechanical interaction between flowing blood and a thrombus is crucial in determining the deformation of the thrombus and the possibility of releasing emboli. In this study, we develop a phase-field model that is capable of describing the structural properties of a thrombus and its biomechanical properties under different blood flow conditions. Moreover, we combine this thrombus model with a particle-based model which simulates the initiation of the thrombus. This combined framework is the first computational study to simulate the development of a thrombus from platelet aggregation to its subsequent viscoelastic responses to various shear flows. Informed by clinical data, this framework can be used to predict the risk of diverse thromboembolic events under physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

The influence of red blood cell (RBC) deformability in whole blood on platelet margination is investigated using confocal microscopy measurements of flowing human blood and cell resolved blood flow simulations. Fluorescent platelet concentrations at the wall of a glass chamber are measured using confocal microscopy with flowing human blood containing varying healthy-to-stiff RBC fractions. A decrease is observed in the fluorescent platelet signal at the wall due to the increase of stiffened RBCs in flow, suggesting a decrease of platelet margination due to an increased fraction of stiffened RBCs present in the flow. In order to resolve the influence of stiffened RBCs on platelet concentration at the channel wall, cell-pair and bulk flow simulations are performed. For homogeneous collisions between RBC pairs, a decrease in final displacement after a collision with increasing membrane stiffness is observed. In heterogeneous collisions between healthy and stiff RBC pairs, it is found that the stiffened RBC is displaced most. The influence of RBC deformability on collisions between RBCs and platelets was found to be negligible due to their size and mass difference. For a straight vessel geometry with varying healthy-to-stiff RBC ratios, a decrease was observed in the red blood cell-free layer and platelet margination due to an increase in stiffened RBCs present in flow. Author summary: The primary function of the human red blood cell is to deliver oxygen to the tissues of the body. The ability of the red blood cell to deform allows it to squeeze through small capillaries along with helping transport platelets to damaged areas on the vessel wall, which initiates normal coagulation function. Many diseases are known to impede the deformability of the red blood cell, which may adversely impact the transport of red blood cells and platelets in flow. We observe that with increasing fractions of stiff red blood cells in flow, there is a decrease of platelet margination. Specifically, this is observed as a decrease of the fluorescent platelet signal at the wall of a glass channel with flowing whole blood. We confirm this margination decrease by performing cell resolved simulations that reproduce the experiments. We also observe, in simulation, a decrease in the red blood cell-free layer as red blood cell deformability decreases. The decrease in the cell-free layer, we believe, is the most significant contributing factor to decreased margination. [ABSTRACT FROM AUTHOR]

Prenatal hypoxia is a gestational stressor that can result in developmental abnormalities or physiological reprogramming, and often decreases cellular capacity against secondary stress. When a developing fetus is exposed to hypoxia, blood flow is preferentially redirected to vital organs including the brain and heart over other organs including the kidney. Hypoxia-induced injury can lead to structural malformations in the kidney; however, even in the absence of structural lesions, hypoxia can physiologically reprogram the kidney leading to decreased function or increased susceptibility to injury. Our investigation in mice reveals that while prenatal hypoxia does not affect normal development of the kidneys, it primes the kidneys to have an increased susceptibility to kidney injury later in life. We found that our model does not develop structural abnormalities when prenatally exposed to modest 12% O2 as evident by normal histological characterization and gene expression analysis. Further, adult renal structure and function is comparable to mice exposed to ambient oxygen throughout nephrogenesis. However, after induction of kidney injury with a nephrotoxin (cisplatin), the offspring of mice housed in hypoxia exhibit significantly reduced renal function and proximal tubule damage following injury. We conclude that exposure to prenatal hypoxia in utero physiologically reprograms the kidneys leading to increased susceptibility to injury later in life. [ABSTRACT FROM AUTHOR]

Background: Kinesiology taping (KT) is used in musculoskeletal practice for preventive and rehabilitative purposes. It is claimed that KT improves blood flow in the microcirculation by creating skin convolutions and that this reduces swelling and facilitates healing of musculoskeletal injuries. There is a paucity of physiological studies evaluating the effect of KT on cutaneous blood microcirculation. Objectives: The purpose of this parallel-group controlled laboratory repeated measures design study was to evaluate the effects of KT on cutaneous blood microcirculation in healthy human adults using a dual wavelength (infrared and visible-red) laser Doppler Imaging (LDI) system. KT was compared with rigid taping and no taping controls to isolate the effects associated with the elasticity of KT Methods: Forty-five healthy male and female human adults were allocated to one of the three interventions using constrained randomisation following the pre-intervention measurement: (i) KT (ii) ST (standard taping) (iii) NT (no taping). Cutaneous blood perfusion was measured using LDI in the ventral surface of forearm at pre-intervention, during-intervention and post-intervention in a normothermic environment at resting conditions. Results: Mixed ANOVA of both infrared and visible-red datasets revealed no statistically significant interaction between Intervention and Time. There was statistically significant main effect for Time but not Intervention. Conclusion: KT does not increase cutaneous blood microcirculation in healthy human adults under resting physiological conditions in a normothermic environment. On the contrary, evidence suggests that taping, regardless of the elasticity in the tape, is associated with immediate reductions in cutaneous blood flow. [ABSTRACT FROM AUTHOR]

Cardiac perfusion PET is increasingly used to assess ischemia and cardiovascular risk and can also provide quantitative myocardial blood flow (MBF) and flow reserve (MBFR) values. These have been shown to be prognostic biomarkers of adverse outcomes, yet MBF and MBFR quantification remains underutilized in clinical settings. We compare MBFR to traditional cardiovascular risk factors in a large and diverse clinical population (60% African-American, 35.3% Caucasian) to rank its relative contribution to cardiovascular outcomes. Major adverse cardiovascular events (MACE), including unstable angina, non-ST and ST-elevation myocardial infarction, stroke, and death, were assessed for consecutive patients who underwent rest-dipyridamole stress 82Rb PET cardiac imaging from 2012–2015 at the Hospital of the University of Pennsylvania (n = 1283, mean follow-up 2.3 years). Resting MBF (1.1 ± 0.4 ml/min/g) was associated with adverse cardiovascular outcomes. MBFR (2.1 ± 0.8) was independently and inversely associated with MACE. Furthermore, MBFR was more strongly associated with MACE than both traditional cardiovascular risk factors and the presence of perfusion defects in regression analysis. Decision tree analysis identified MBFR as superior to established cardiovascular risk factors in predicting outcomes. Incorporating resting MBF and MBFR in CAD assessment may improve clinical decision making. [ABSTRACT FROM AUTHOR]

We present a multi-disciplinary image-based blood flow perfusion modeling of a whole organ vascular network for analyzing both its structural and functional properties. We show how the use of Light-Sheet Fluorescence Microscopy (LSFM) permits whole-organ micro-vascular imaging, analysis and modelling. By using adapted image post-treatment workflow, we could segment, vectorize and reconstruct the entire micro-vascular network composed of 1.7 million vessels, from the tissue-scale, inside a ∼ 25 × 5 × 1 = 125mm3 volume of the mouse fat pad, hundreds of times larger than previous studies, down to the cellular scale at micron resolution, with the entire blood perfusion modeled. Adapted network analysis revealed the structural and functional organization of meso-scale tissue as strongly connected communities of vessels. These communities share a distinct heterogeneous core region and a more homogeneous peripheral region, consistently with known biological functions of fat tissue. Graph clustering analysis also revealed two distinct robust meso-scale typical sizes (from 10 to several hundred times the cellular size), revealing, for the first time, strongly connected functional vascular communities. These community networks support heterogeneous micro-environments. This work provides the proof of concept that in-silico all-tissue perfusion modeling can reveal new structural and functional exchanges between micro-regions in tissues, found from community clusters in the vascular graph. Author summary: New optical microscopy called light-sheet fluorescence microscopy (LSFM) allows for 3D optical scan imaging of an entire tissue, at the micron scale, for reconstructing its complete microvascular bed. The 3D reconstruction of a vectorized vascular network can display as many as 1.7 million vessels inside a 125mm3 volume of mouse fat tissue. This 3D reconstruction allows for vessel visualisation and also the complete virtual "dissection" and analysis of the vascular bed. Described as a graph, the vascular network provides a new tissue anatomy description, similar to city maps built on a road graph, showing structural clusters emerging as tissue "districts". These clusters provide a new basis for lobule description in fat tissue. Even more can be obtained from virtual perfusion simulated inside the tissue by using in-silico modeling tools. This virtual perfusion reveals the functional properties of the vascular network, such as perfusion fluxes, and exchanges between clusters and infusion time (time for the blood to reach a site from the principal entry). [ABSTRACT FROM AUTHOR]

Many experiments have documented the response of intraocular pressure (IOP) to postural change. External forces caused by gravitational orientation change produce a dynamic response that is encountered every day during normal activities. Tilting the body at a small downward angle is also relevant to studying the effects of hypogravity (spaceflight), including ocular changes. We examined data from 36 independent datasets from 30 articles on IOP response to postural change, representing a total population of 821 subjects (≥1173 eyes) with widely varying initial and final postures. We confirmed that IOP was well predicted by a simple quantity, namely the hydrostatic pressure at the level of the eye, although the dependence was complex (nonlinear). Our results show that posturally induced IOP change can be explained by hydrostatic forcing plus an autoregulatory contribution that is dependent on hydrostatic effects. This study represents data from thousands of IOP measurements and provides insight for future studies that consider postural change in relation to ocular physiology, intraocular pressure, ocular blood flow and aqueous humor dynamics. [ABSTRACT FROM AUTHOR]

In vertebrates, the embryonic environment is known to affect the development and the health of individuals. In broiler chickens, the thermal-manipulation (TM) of eggs during the incubation period was shown to improve heat tolerance at slaughter age (35 days of age) in association with several modifications at the molecular, metabolic and physiological levels. However, little is known about the Japanese quail (Coturnix japonica), a closely related avian species widely used as a laboratory animal model and farmed for its meat and eggs. Here we developed and characterized a TM procedure (39.5°C and 65% relative humidity, 12 h/d, from days 0 to 13 of incubation) in quails by analyzing its short and long-term effects on zootechnical, physiological and metabolic parameters. Heat-tolerance was tested by a heat challenge (36°C for 7h) at 35 days of age. TM significantly reduced the hatching rate of the animals and increased mortality during the first four weeks of life. At hatching, TM animals were heavier than controls, but lighter at 25 days of age for both sexes. Thirty-five days after hatching, TM decreased the surface temperature of the shank in females, suggesting a modulation of the blood flow to maintain the internal temperature. TM also increased blood partial pressure and oxygen saturation percentage at 35 days of age in females, suggesting a long-term modulation of the respiration physiology. Quails physiologically responded to the heat challenge, with a modification of several hematologic and metabolic parameters, including an increase in plasma corticosterone concentration. Several physiological parameters such as beak surface temperature and blood sodium concentration revealed that TM birds responded differently to the heat challenge compared to controls. Altogether, this first comprehensive characterization of TM in Japanese quail showed durable effects that may affect the response of TM quails to heat. [ABSTRACT FROM AUTHOR]

Aortic valve disease is one of the leading forms of complications in the cardiovascular system. The failing native aortic valve is routinely surgically replaced with a bioprosthesis. However, insufficient durability of bioprosthetic heart valves often requires reintervention. Valve degradation can be assessed by an analysis of the blood flow characteristics downstream of the valve. This is cost and labor intensive using clinical methodologies and is performed infrequently. The integration of consumer smartphones and implantable blood flow sensors into the data acquisition chain facilitates remote management of patients that is not limited by access to clinical facilities. This article describes the characteristics of an implantable magnetic blood flow sensor which was optimized for small size and low power consumption to allow for batteryless operation. The data is wirelessly transmitted to the patient's smartphone for in-depth processing. Tests using three different experimental setups confirmed that wireless and batteryless blood flow recording using a magnetic flow meter technique is feasible and that the sensor system is capable of monitoring the characteristic flow downstream of the valve. [ABSTRACT FROM AUTHOR]

Background: Recently, porous acupuncture (PA), which is anodized to increase its surface area for higher stimulation intensity, was developed and showed significantly improved therapeutic effects with more comfort as compared with original acupuncture (OA) in vivo. However, the impact of PA on the change of local blood flow as well as its efficacy and acceptability has not yet been confirmed in a clinical trial. In a randomized, controlled crossover clinical trial, we investigated the effects of PA on the change in local blood flow using laser Doppler perfusion imaging and considered the sensation of pain intensity and discomfort severity using a visual analogue scale (VAS) to explore its physiological impact and the possibility of PA in clinical use. Methods: Twenty-one healthy participants were randomly treated with PA or OA on one side of Zusanli (ST36) and each participant served as his or her own control. Baseline local blood flow and galvanic skin response (GSR) were obtained for 5 min and acupuncture interventions were subsequently performed. Next, local blood flow and GSR were subsequently obtained for 10 min after insertion, 10 min after manipulation, and 5 min after the withdrawal of acupuncture. At the end of the experiment, participants were asked to indicate the sensation of pain intensity at each session of insertion, retention, manipulation, and withdrawal as well as the overall pain intensity and discomfort severity. Results: PA significantly increased the local blood flow as compared with OA and there was no significant difference in GSR between patients treated with PA versus OA in each phase of insertion and manipulation. No significant difference in pain intensity or discomfort severity was found during manipulation, retention, or withdrawal of acupuncture. Conclusions: These results indicate that PA increases local blood flow, which can be closely related to the observed enhanced performance, without any associated discomfort or pain, suggesting its applicability in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Neck compression collars have been proposed to reduce injury to the brain caused by head impacts. Our objective was to test if compression of the carotid artery affected the baroreflex and influenced blood pressure control. Methods: Cerebrovascular and autonomic responses of healthy young men and women (n = 8 each) to paced deep breathing, Valsalva, and 70o head-up tilt with or without use of a Q-collar were determined. Continuous measurements of heart rate, beat-to-beat blood pressure, transcranial Doppler, and end-tidal gases were obtained. Heart rate variability was measured during supine rest and head-up tilt. Carotid artery and jugular vein cross-sectional area were measured at end-inhalation and end-exhalation using cross-sectional ultrasound images at diastole. Results: Wearing the collar reduced carotid cross-sectional area (CSA; P = 0.022; η2 = 0.03) and increased jugular CSA (P = 0.001; η 2 = 0.30). In both men and women, wearing the collar increased systolic blood pressure during Valsalva (P<0.05; η 2 = 0.38). In only men, wearing the collar resulted in prolonged pressure recovery time during Valsalva (P = 0.02; η 2 = 0.05). In only women, wearing the collar increased baseline diastolic (P = 0.026; η 2 = 0.09) and mean (P = 0.041; η 2 = 0.06) middle cerebral artery (MCA) blood flow velocity, which attenuated the normal increase of diastolic (P = 0.01; η 2 = 0.03) and mean (P = 0.038; η 2 = 0.02) MCA blood flow velocity during Valsalva. There were no effects of sex or collar on the responses to deep breathing (P>0.05), and there were no effects of the collar on cerebrovascular function, hemodynamics, cardiovagal baroreceptor sensitivity, or heart rate variability (P>0.05) during upright tilt. Conclusion: Use of the Q-collar compresses both the jugular vein and carotid artery influencing sympathetic nerve activity in both men and women while influencing brain blood flow in women. [ABSTRACT FROM AUTHOR]

We recently provided highly suggestive preliminary evidence that the renal interstitium contracts reactively in vivo. We demonstrated that renal medullary direct interstitial volume expansion (rmDIVE = 100 μl bolus infusion of 0.9% saline (SS)/30 s) brought about a biphasic renal interstitial hydrostatic pressure (RIHP) response which was abolished when dibutyryl-cAMP was concomitant and interstitially infused. To assess more deeply the feasibility of the concept that the renal interstitium contracts in vivo, two experimental series (S1, S2) were performed in hydropenic rats subjected to acute left renal-denervation, hormonal clamping, and control of renal arterial pressure. In S1, RIHP and renal outer medullary blood flow (RoMBF) were continuously measured before and after a sudden micro-bolus (5μl) injection, into the renal medullary interstitium, of SS containing α-trinositol (α-TNS, anti-inflammatory drug) to either two doses 2 or 4 mM (SS + 2 α-TNS and SS + 4 α-TNS groups). No overall differences between groups in either ΔRIHP or %ΔRoMBF time courses were found; however, in the SS + 2 α-TNS group the data were less scattered and the ΔRIHP time course tended to peak faster and then persisted there, so that, this α-TNS dose was selected for S2. In S2, RIHP and RoMBF were similarly measured in rats randomly assigned to three groups: the CTR group (sham time-control), SS group (SS alone), and SS + α-TNS group. The micro-bolus injection of SS alone (SS group) was unable to increase ΔRIHP. The group with no micro-bolus injection (CTR group) experienced a decrease in ΔRIHP. The micro-bolus injection of SS + 2 α-TNS was accompanied by a differential increase in ΔRIHP (vs. CTR and SS groups). These responses were not associated with differential changes among groups in %ΔRoMBF or hemodilution parameters. These results provide additional evidence that the renal interstitium contracts in vivo. [ABSTRACT FROM AUTHOR]

Background: The upright posture imposes a significant challenge to blood pressure regulation that is compensated through baroreflex-mediated increases in heart rate and vascular resistance. Orthostatic cardiac responses are easily inferred from heart rate, but vascular resistance responses are harder to elucidate. One approach is to determine vascular resistance as arterial pressure/blood flow, where blood flow is inferred from ultrasound-based measurements of brachial blood velocity. This relies on the as yet unvalidated assumption that brachial artery diameter does not change during orthostatic stress, and so velocity is proportional to flow. It is also unknown whether the orthostatic vascular resistance response is related to initial blood vessel diameter. Methods: We determined beat-to-beat heart rate (ECG), blood pressure (Portapres) and vascular resistance (Doppler ultrasound) during a combined orthostatic stress test (head-upright tilting and lower body negative pressure) continued until presyncope. Participants were 16 men (aged 38.4±2.3 years) who lived permanently at high altitude (4450m). Results: The supine brachial diameter ranged from 2.9–5.6mm. Brachial diameter did not change during orthostatic stress (supine: 4.19±0.2mm; tilt: 4.20±0.2mm; -20mmHg lower body negative pressure: 4.19±0.2mm, p = 0.811). There was no significant correlation between supine brachial artery diameter and the maximum vascular resistance response (r = 0.323; p = 0.29). Forearm vascular resistance responses evaluated using brachial arterial flow and velocity were strongly correlated (r = 0.989, p<0.00001) and demonstrated high equivalency with minimal bias (-6.34±24.4%). Discussion: During severe orthostatic stress the diameter of the brachial artery remains constant, supporting use of brachial velocity for accurate continuous non-invasive orthostatic vascular resistance responses. The magnitude of the orthostatic forearm vascular resistance response was unrelated to the baseline brachial arterial diameter, suggesting that upstream vessel size does not matter in the ability to mount a vasoconstrictor response to orthostasis. [ABSTRACT FROM AUTHOR]

4D and 2D phase-contrast MRI (2D Flow MRI, 4D Flow MRI, respectively) are increasingly being used to noninvasively assess pulmonary hypertension (PH). The goals of this study were i) to evaluate whether established quantitative parameters in 2D Flow MRI associated with pulmonary hypertension can be assessed using 4D Flow MRI; ii) to compare results from 4D Flow MRI on a digital broadband 3T MR system with data from clinically established MRI-techniques as well as conservation of mass analysis and phantom correction and iii) to elaborate on the added value of secondary flow patterns in detecting PH. 11 patients with PH (4f, 63 ± 16y), 15 age-matched healthy volunteers (9f, 56 ± 11y), and 20 young healthy volunteers (13f, 23 ± 2y) were scanned on a 3T MR scanner (Philips Ingenia). Subjects were examined with a 4D Flow, a 2D Flow and a bSSFP sequence. For extrinsic comparison, quantitative parameters measured with 4D Flow MRI were compared to i) a static phantom, ii) 2D Flow acquisitions and iii) stroke volume derived from a bSSFP sequence. For intrinsic comparison conservation of mass-analysis was employed. Dedicated software was used to extract various flow, velocity, and anatomical parameters. Visualization of blood flow was performed to detect secondary flow patterns. Overall, there was good agreement between all techniques, 4D Flow results revealed a considerable spread. Data improved after phantom correction. Both 4D and 2D Flow MRI revealed concordant results to differentiate patients from healthy individuals, especially based on values derived from anatomical parameters. The visualization of a vortex, indicating the presence of PH was achieved in 9 /11 patients and 2/35 volunteers. This study confirms that quantitative parameters used for characterizing pulmonary hypertension can be gathered using 4D Flow MRI within clinically reasonable limits of agreement. Despite its unfavorable spatial and lesser temporal resolution and a non-neglible spread of results, the identification of diseased study participants was possible. [ABSTRACT FROM AUTHOR]

Introduction: While extracorporeal membrane oxygenation (ECMO) is effective in preventing further hypoxemia and maintains blood flow in endotoxin-induced shock, ECMO alone does not reverse the hypotension. In this study, we tested whether concurrent vasopressor use with ECMO would provide increased circulatory support and blood flow, and characterized regional blood flow distribution to vital organs. Methods: Endotoxic shock was induced in piglets to achieve a 30% decrease in mean arterial pressure (MAP). Measurements of untreated pigs were compared to pigs treated with ECMO alone or ECMO and vasopressors. Results: ECMO provided cardiac support during vasodilatory endotoxic shock and improved oxygen delivery, but vasopressor therapy was required to return MAP to normotensive levels. Increased blood pressure with vasopressors did not alter oxygen consumption or extraction compared to ECMO alone. Regional microcirculatory blood flow (RBF) to the brain, kidney, and liver were maintained or increased during ECMO with and without vasopressors. Conclusion: ECMO support and concurrent vasopressor use improve regional blood flow and oxygen delivery even in the absence of full blood pressure restoration. Vasopressor-induced selective distribution of blood flow to vital organs is retained when vasopressors are administered with ECMO. [ABSTRACT FROM AUTHOR]

Purpose: To investigate if there are differences in macular capillaries between black and white subjects using optical coherence tomography angiography (OCTA) and identify potential factors underlying the epidemiologically-based higher vulnerability of black populations to diabetic retinopathy (DR). Methods: This prospective, observational cross-sectional study included 93 eyes of 47 healthy subjects with no medical history and ocular history who self-identified as black or white and were matched for age, sex, refractive error, and image quality. Subjects underwent OCTA imaging (RTVue-XR Avanti) of the superficial (SCP) and deep (DCP) capillary plexuses and choriocapillaris. AngioAnalytics was used to analyze vessel density (VD) and choriocapillaris % blood flow area (BFA) in the 1mm-diameter fovea, parafovea, and 3mm-diameter circular area including the fovea and parafovea (3x3mm image). Foveal avascular zone (FAZ) was also analyzed. Linear mixed models were used to evaluate for differences between the study groups. Results: Compared to the white subjects in this study, black subjects were found to have: lower foveal VD in the SCP (p<0.05); lower VD in the parafovea and in the 3x3mm image in the DCP (p<0.05); larger FAZ in SCP and DCP (p<0.05); and decreased choriocapillary BFA in the area underlying the fovea, parafovea, and 3x3mm image (p<0.05). Conclusion: In our study, our black subjects had decreased macular capillary vasculature compared to matched white subjects, even in early adulthood and the absence of any systemic or ocular conditions. To our knowledge, this is the first report showing that retinal and choriocapillary vascular differences may contribute to racial disparities in vulnerability to DR. [ABSTRACT FROM AUTHOR]

Echocardiography, as a noninvasive hemodynamic evaluation technique, is frequently used in critically ill patients. Different opinions exist regarding whether it can be interchanged with traditional invasive means, such as the pulmonary artery catheter thermodilution (TD) technique. This systematic review aimed to analyze the consistency and interchangeability of cardiac output measurements by ultrasound (US) and TD. Five electronic databases were searched for studies including clinical trials conducted up to June 2019 in which patients’ cardiac output was measured by ultrasound techniques (echocardiography) and TD. The methodological quality of the included studies was evaluated by two independent reviewers who used the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), which was tailored according to our systematic review in Review Manager 5.3. A total of 68 studies with 1996 patients were identified as eligible. Meta-analysis and subgroup analysis were used to compare the cardiac output (CO) measured using the different types of echocardiography and different sites of Doppler use with TD. No significant differences were found between US and TD (random effects model: mean difference [MD], -0.14; 95% confidence interval, -0.30 to 0.02; P = 0.08). No significant differences were observed in the subgroup analyses using different types of echocardiography and different sites except for ascending aorta (AA) (random effects model: mean difference [MD], -0.37; 95% confidence interval, -0.74 to -0.01; P = 0.05) of Doppler use. The median of bias and limits of agreement were -0.12 and ±0.94 L/min, respectively; the median of correlation coefficient was 0.827 (range, 0.140–0.998). Although the difference in CO between echocardiography by different types or sites and TD was not entirely consistent, the overall effect of meta-analysis showed that no significant differences were observed between US and TD. The techniques may be interchangeable under certain conditions. [ABSTRACT FROM AUTHOR]

Various methods have been devised to dissolve hydrogen gas in organ preservation solutions, including use of a hydrogen gas cylinder, electrolysis, or a hydrogen-generating agent. However, these methods require considerable time and effort for preparation. We investigated a practical technique for rapidly dissolving hydrogen gas in organ preservation solutions by using a canister containing hydrogen-absorbing alloy. The efficacy of hydrogen-containing organ preservation solution created by this method was tested in a miniature pig model of kidney transplantation from donors with circulatory arrest. The time required for dissolution of hydrogen gas was only 2–3 minutes. When hydrogen gas was infused into a bag containing cold ETK organ preservation solution at a pressure of 0.06 MPa and the bag was subsequently opened to the air, the dissolved hydrogen concentration remained at 1.0 mg/L or more for 4 hours. After warm ischemic injury was induced by circulatory arrest for 30 minutes, donor kidneys were harvested and perfused for 5 minutes with hydrogen-containing cold ETK solution or hydrogen-free cold ETK solution. The perfusion rate was faster from the initial stage with hydrogen-containing cold ETK solution than with hydrogen-free ETK solution. After storage of the kidney in hydrogen-free preservation solution for 1 hour before transplantation, no urine production was observed and blood flow was not detected in the transplanted kidney at sacrifice on postoperative day 6. In contrast, after storage in hydrogen-containing preservation solution for either 1 or 4 hours, urine was detected in the bladder and blood flow was confirmed in the transplanted kidney. This method of dissolving hydrogen gas in organ preservation solution is a practical technique for potentially converting damaged organs to transplantable organs that can be used safely in any clinical setting where organs are removed from donors. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was the assessment of volumetric CT-perfusion (CTP) of the lower leg musculature in patients with symptomatic peripheral arterial disease (PAD) of the lower extremities, comparing it with established angiographic and hemodynamic parameters. Materials and methods: Thirty-five consecutive patients with symptomatic PAD of the lower extremities requiring interventional revascularization were assessed prospectively. All patients underwent a CTP scan of the lower leg, and hemodynamic and angiographic assessment. Hemodynamic parameters, specifically ankle-brachial pressure index (ABI), ankle blood pressure (ABP), peak systolic velocity (PSV), and segmental pulse oscillography (SPO) level, were determined. Lesion length and degree of collateralization were assessed by interventional angiography. CTP parameters were calculated with a perfusion software, acting on a no outflow assumption. A sequential two-compartment model was used. Differences in CTP parameters and correlations between CTP, hemodynamic and angiographic parameters were assessed with non-parametric tests. Results: The cohort consisted of 27 subjects with an occlusion, and eight with a high-grade stenosis. The mean blood flow (BF) was 7.71 ± 2.96 ml/100ml*min-1, mean blood volume (BV) 0.71 ± 0.33 ml/100ml, and mean mean transit time (MTT) 7.22 ± 2.66 s. BF and BV were higher in subjects with longer lesions, and BV was higher in subjects with lower ABI. Significant correlations were found between lesion length and BV (r = 0.65) and BF (r = 0.52). Significant inverse correlations were found between BV and ABI and between BV and ABP (r = -0.56, for both correlations). Conclusions: In our study, we have shown the feasibility of CTP for the assessment of PAD. In the future, this quantitative method might serve as a non-invasive method, possibly complementing the diagnostic workup of patients with peripheral arterial disease. [ABSTRACT FROM AUTHOR]

The blood flow through the major vessels holds great diagnostic potential for the identification of cardiovascular complications and is therefore routinely assessed with current diagnostic modalities. Heart valves are subject to high hydrodynamic loads which render them prone to premature degradation. Failing native aortic valves are routinely replaced with bioprosthetic heart valves. This type of prosthesis is limited by a durability that is often less than the patient’s life expectancy. Frequent assessment of valvular function can therefore help to ensure good long-term outcomes and to plan reinterventions. In this article, we describe how unsupervised novelty detection algorithms can be used to automate the interpretation of blood flow data to improve outcomes through early detection of adverse cardiovascular events without requiring repeated check-ups in a clinical environment. The proposed method was tested in an in-vitro flow loop which allowed simulating a failing aortic valve in a laboratory setting. Aortic regurgitation of increasing severity was deliberately introduced with tube-shaped inserts, preventing complete valve closure during diastole. Blood flow recordings from a flow meter at the location of the ascending aorta were analyzed with the algorithms introduced in this article and a diagnostic index was defined that reflects the severity of valvular degradation. The results indicate that the proposed methodology offers a high sensitivity towards pathological changes of valvular function and that it is capable of automatically identifying valvular degradation. Such methods may be a step towards computer-assisted diagnostics and telemedicine that provide the clinician with novel tools to improve patient care. [ABSTRACT FROM AUTHOR]

Perfusion-related information is reportedly embedded in the low-frequency component of a blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal. The blood-propagation pattern through the cerebral vascular tree is detected as an interregional lag variation of spontaneous low-frequency oscillations (sLFOs). Mapping of this lag, or phase, has been implicitly treated as a projection of the vascular tree structure onto real space. While accumulating evidence supports the biological significance of this signal component, the physiological basis of the “perfusion lag structure,” a requirement for an integrative resting-state fMRI-signal model, is lacking. In this study, we conducted analyses furthering the hypothesis that the sLFO is not only largely of systemic origin, but also essentially intrinsic to blood, and hence behaves as a virtual tracer. By summing the small fluctuations of instantaneous phase differences between adjacent vascular regions, a velocity response to respiratory challenges was detected. Regarding the relationship to neurovascular coupling, the removal of the whole lag structure, which can be considered as an optimized global-signal regression, resulted in a reduction of inter-individual variance while preserving the fMRI response. Examination of the T2* and S0, or non-BOLD, components of the fMRI signal revealed that the lag structure is deoxyhemoglobin dependent, while paradoxically presenting a signal-magnitude reduction in the venous side of the cerebral vasculature. These findings provide insight into the origin of BOLD sLFOs, suggesting that they are highly intrinsic to the circulating blood. [ABSTRACT FROM AUTHOR]

Objectives: This systematic review aimed to evaluate the therapeutic effects and safety of Chinese herbal medicine (CHM) formulae for managing menopausal hot flushes (MHF). Methods: Seven English and Chinese databases were searched for studies from respective inceptions to February 2019. Randomized controlled trials investigating the clinical effects and safety of CHM formulae on MHF were considered for inclusion. The outcomes of subjective feelings (MHF and quality of life), objective changes (hormones and peripheral blood flow) and safety were analyzed. The most frequently prescribed formulae and herbs were summarized. Results: Nineteen randomized clinical trials involving 2469 patients were included. When compared to menopausal hormone therapy, CHM had similar effects to menopausal hormone therapy on total effectiveness rate (OR 1.41, 95% CI 0.84 to 2.35) and total Kupperman index (KI) score (SMD -0.13, 95% CI -0.61 to 0.36), and could significantly reduce vasomotor symptom score (MD -0.43, 95% CI -0.55 to -0.31) and upper-body peripheral blood flow (MD -3.56, 95% CI -5.14 to -1.98 under the jaw, MD -7.10, 95% CI -11.01 to -3.19 in the fingertip). When compared to placebo, CHM could reduce MHF severity (MD -0.70, 95% CI-1.00 to -0.40) and improve total KI score (MD -12.61, 95% CI -15.21 to -10.01). However, no statistically significant changes to hormone levels were detected. Most commonly seen adverse events were mild gastrointestinal tract reactions. The most popularly studied formula was Kun Tai capsule and the most frequently prescribed herb was Bai shao (Paeoniae Radix Alba, Paeonia lactiflora Pall.). More than 50% included studies had low risks of bias in the domains of selection, performance, attrition and reporting. Conclusions: This review indicated that CHM formulae were safe to be applied in MHF females and able to improve MHF-related symptom scores as well as the peripheral blood flow. Further studies should focus on specific formulae. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between sympathetic activity, reactive hyperemia and brachial artery flow-mediated dilation (FMD). Background: It is claimed that major surgery has an impact on endothelial function, as observed by post-operative reduced brachial artery FMD response. However, another explanation for the observed reduced FMD response post-operatively may be sympathetic stress-induced reduction in blood flow. Methods: Seventeen healthy volunteers with a median age (25th-75th percentiles) of 23.5 (23–24.8) years were recruited. Participants’ brachial blood flow and FMD response were measured (i) during normal non-stress conditions (Normal1); (ii) during exposure to ice water; and (iii) afterwards, under normal non-stress conditions (Normal2). We continuously measured arterial blood pressure (Finometer), heart rate (ECG), skin blood flow of the index finger (laser Doppler), and brachial artery blood flow and diameter (Ultrasound Doppler). Measurements were taken at baseline; before a 5-min suprasystolic forearm occlusion; and following a 3-min post-occlusion, to measure reactive hyperemia and FMD. Results: Median (25th-75th percentiles) FMD response after exposure to ice water was reduced compared to non-stress conditions [4.9 (2.9–8.4) % during ice water vs. 9.7 (7.6–12.2) % Normal1 and 9.7 (6.4–10.3) % Normal2, P < 0.001]. Blood flow 60 s after cuff-deflation during ice water exposure was significantly reduced to 328 (289–421) mL compared to non-stress conditions (both P < 0.05). No differences were observed between Normal1 [446 (359–506) mL] and Normal2 [455 (365–515) mL] (both P > 0.05). Heart rate significantly increased during ice water exposure [67 (59–69) beats/min)] compared to 55 (49–60) beats/min during Normal1 and 54 (47–60) beats/min during Normal2 (both P < 0.05). MAP did not change during Normal1 [72 (64–84)] or during Normal2 [71 (65–81) mm Hg] (both P > 0.05), but increased to 86 (75–98) mm Hg during ice water exposure (P < 0.05). Conclusions: Increased sympathetic activity resulted in decreased blood flow and brachial artery FMD response in healthy volunteers, independent of endothelial dysfunction. Future studies should adjust for blood flow when interpreting the FMD response. [ABSTRACT FROM AUTHOR]

Background: It is not clear whether the configuration of the posterior part of the circle of Willis (CW) depends on the proximal part of the vertebrobasilar system. Our aim is to evaluate the posterior part of CW in association with different size of vertebral arteries (VA) in healthy volunteers. Materials and methods: The present study was based on a sample of 923 healthy volunteers who were examined from 2013 through 2018. The duplex ultrasonographic examination of the extracranial vertebral (VA) and carotid arteries was performed. VA was defined as hypoplastic (VAH) when VA diameter in the entire course was less than 2.5 mm. All the participants underwent magnetic resonance angiography (MRA) examination. All the component vessels of the circle of Willis were assessed in each individual. We classified the posterior communicating artery (PCoA) as presence PCoA, absence/hypoplastic PCoA and fetal-type posterior circle of Willis (FCW) in which the major stem of the posterior cerebral artery (PCA) arises from ipsilateral internal carotid artery (ICA). The comparison of the posterior part of CW was made in subjects with normal VA and VAH of a different degree (communicating with basilar artery (VAH-BA) and not communicating with the basilar artery (VAH-PICA)). Results: FCW was found in 15.9% of subjects, bilaterally–in 2.3%. FCW was more frequent in individuals with VAH than in those with normal VA (accordingly, 28.8% vs. 13.5%, p<0.001. Moreover FCW was recorded in 50% of the subjects with VA—PICA in comparison with 13.5% of those with normal VA and 22.8% with VAH—BA, p<0.005. On the contrary, absence/hypoplasia of both PCoA was mostly found in the group with normal VA in comparison with VAH-BA and VAH-PICA (accordingly, 50.7%, 38.6% and 12.5%, p<0.01). Conclusion: Individuals with VAH have a different pattern of the posterior part of CW in comparison with those with normal VA. With the increasing degree of VAH, the proportion of FCW increases, while the proportion of absence/hypoplastic of both PCoA decreases. [ABSTRACT FROM AUTHOR]

Introduction: Mechanical cardiopulmonary resuscitation (CPR) devices are widely used to rescue patients from cardiac arrest. This study aimed to compare hemodynamic effects and resuscitation outcomes between a motor-driven, automatic simultaneous sterno-thoracic cardiopulmonary resuscitation device and the Lund University cardiac arrest system (LUCAS). Material and methods: After 2 minutes of electrically induced ventricular fibrillation (VF), Yorkshire pigs (weight 35–60 kg) received CPR with an automatic simultaneous sterno-thoracic CPR device (X-CPR group, n = 13) or the Lund University cardiac arrest system (LUCAS group, n = 12). Basic life support for 6 minutes and advanced cardiovascular life support for 12 minutes, including defibrillation and epinephrine administration, were provided. Hemodynamic parameters and resuscitation outcomes, including return of spontaneous circulation (ROSC), 24-hour survival, and cerebral performance category (CPC) at 24 hours, were evaluated. Results: Hemodynamic parameters, including aortic pressures, coronary perfusion pressure, carotid blood flow, and end-tidal carbon dioxide pressure were not significantly different between the two groups. Resuscitation outcomes were also not significantly different between the groups (X-CPR vs. LUCAS; rate of ROSC: 31% vs 25%, p = 1.000; 24-hour survival rate: 31% vs 17%, p = 0.645; neurological outcome with CPC ≤2: 31% vs 17%, p = 0.645). Also no significant difference in incidence complications associated with resuscitation was found between the groups. Conclusions: CPR with a motor-driven X-CPR and CPR with the LUCAS produced similar hemodynamic effects and resuscitation outcomes in a swine model of cardiac arrest. [ABSTRACT FROM AUTHOR]

Chronic atherosclerosis may cause cerebral hypoperfusion and inadequate brain oxygenation, contributing to the progression of cognitive decline. In this study, we exploited two-photon phosphorescence lifetime microscopy to measure the absolute partial pressure of oxygen (PO2) in cortical tissue in both young and old LDLR-/-, hApoB100+/+ mice, spontaneously developing atherosclerosis with age. Capillary red-blood-cell (RBC) speed, flux, hematocrit and capillary diameter were also measured by two-photon imaging of FITC-labelled blood plasma. Our results show positive correlations between RBC speed, flux, diameter and capillary-adjacent tissue PO2. When compared to the young mice, we observed lower tissue PO2, lower RBC speed and flux, and smaller capillary diameter in the old atherosclerotic mice. The old mice also exhibited a higher spatial heterogeneity of tissue PO2, and RBC speed and flux, suggesting a less efficient oxygen extraction. [ABSTRACT FROM AUTHOR]

Ischemia reperfusion (IR) injury can cause acute kidney injury. It has previously been reported that kidney oxygen consumption (QO2) in relation to glomerular filtration rate (GFR), and thus tubular sodium load, is markedly increased following IR injury, indicating reduced electrolyte transport efficiency. Since proximal tubular sodium reabsorption (TNa) is a major contributor to overall kidney QO2, we investigated whether inhibition of proximal tubular sodium transport through carbonic anhydrase (CA) inhibition would improve renal oxygenation following ischemia reperfusion. Anesthetized adult male Sprague Dawley rats were administered the CA inhibitor acetazolamide (50 mg/kg bolus iv), or volume-matched vehicle, and kidney function, hemodynamics and QO2 were estimated before and after 45 minutes of unilateral complete warm renal ischemia. CA inhibition per se reduced GFR (-20%) and TNa (-22%), while it increased urine flow and urinary sodium excretion (36-fold). Renal blood flow was reduced (-31%) due to increased renal vascular resistance (+37%) without affecting QO2. IR per se resulted in similar decrease in GFR and TNa, independently of CA activity. However, the QO2/TNa ratio following ischemia-reperfusion was profoundly increased in the group receiving CA inhibition, indicating a significant contribution of basal oxygen metabolism to the total kidney QO2 following inhibition of proximal tubular function after IR injury. Ischemia increased urinary excretion of kidney injury molecule-1, an effect that was unaffected by CA. In conclusion, this study demonstrates that CA inhibition further impairs renal oxygenation and does not protect tubular function in the acute phase following IR injury. Furthermore, these results indicate a major role of the proximal tubule in the acute recovery from an ischemic insult. [ABSTRACT FROM AUTHOR]