Blood Flow Levels Research Articles

Effect of Micro Acupotomy and Stellate Ganglion Stimulation on Patients with Cervical Vertigo

This article aims to evaluate the treatment effect of micro acupotomy and stellate ganglion stimulation on cervical vertigo. 90 patients with cervical vertigo were randomly divided into two groups, observation group and control group, with 45 cases in each group. The observation group was given micro acupotomy and stellate ganglion stimulation and the control group was given regular acupuncture treatment. The two groups were treated for 2 w. The therapeutic effect and evaluation of symptoms and functions of cervical vertigo score of the two groups of patients after treatment were observed. The mean blood flow levels of vertebrobasilar artery, right vertebral artery and left vertebral artery before and after treatment were observed. The results show that there were significant differences in mean changes of vertigo symptoms and functional scores between the two groups of patients (p<0.01) and the improvement of the observation group was larger than that of the control group (p<0.05); there was significant difference in the speeds of the blood flow of the vertebral-basal artery between the two groups before and after treatment (p<0.05) and the improvement of the observation group was larger than that of the control group (p<0.05). By comparison, the clinical effects of the two groups were statistically different (p<0.05), no side effects occurred in the two groups of patients. Micro acupotomy combined with stellate ganglion stimulation is effective in treating cervical vertigo.

The relationship between impaired uteroplacental blood flow and blood pressure level in pregnant women with chronic and gestational hypertension

Aim. To assess the relationship between impaired uteroplacental blood flow and different levels of blood pressure in pregnant women with chronic and gestational hypertension at different stages of pregnancy with the determination of the optimal systolic blood pressure.&#x0D; Methods. We conducted a prospective cohort study between 2018 and 2019. The study enrolled pregnant women aged 18 to 45 years: 55 women with chronic and gestational hypertension each, as well as 80 healthy pregnant women as control. The groups were formed by the continuous method, in which all pregnant women with arterial hypertension were included in the study until the required number of subjects was obtained. Follow-up was conducted at different gestation periods (1416, 2022, 2830, 3436 weeks) until delivery. Independent groups were compared by using the Student's t-test, the Pearsons 2 test, the MannWhitney U test, the KruskalWallis H test.&#x0D; Results. Comparison of the groups revealed differences in blood pressure levels at different gestation periods. In chronic hypertension compared with gestational hypertension, there was an increase in the impairment of the uteroplacental blood flow in pregnant women, indicating an unfavorable prognosis. The study of impaired uteroplacental blood flow among pregnant women with various forms of arterial hypertension revealed an increase in pregnant women with chronic arterial hypertension compared with gestational (p=0.04), indicating an unfavorable prognosis. In chronic arterial hypertension, the impairment of uteroplacental blood flow was the least for systolic pressures up to 120 mm Hg (up to 0.9%) at 1416 and 2022 weeks of gestation, and for 130139 mm Hg (from 1.8 to 2.7%) in later pregnancy. In gestational hypertension, the least or no impairment rate of uteroplacental blood flow was determined for blood pressures up to 129 mm Hg at all stages of pregnancy compared with chronic hypertension.&#x0D; Conclusion. The optimal systolic blood pressure in chronic hypertension reducing the risk of impaired uteroplacental blood flow in pregnant women is 129 mm Hg before 20th week of pregnancy and 130139 mm Hg in later (2030 weeks); in gestational hypertension, blood pressure reduction to 129 mm Hg is recommended at all stage of gestation.

Interrelation of cognitive functions and neural networks with blood flow velocity through the internal jugular vein in patients with chronic cerebral ischemia

Understanding age-related and functional changes in cerebral venous circulation is critical for the development of new preventive, diagnostic and therapeutic approaches to maintaining brain health in the elderly. Chronic cerebral ischemia is one of the widespread socially significant vascular diseases caused by a decrease in the level of blood circulation. To assess the role of venous outflow through the internal jugular veins in cognitive decline and neural networks in patients with chronic cerebral ischemia, 30 men and 40 women (average age 66.5 years), cognitive functions and organization of neural networks were studied at high and low levels of cerebral venous blood flow through the internal jugular veins. To assess the venous outflow, the systolic blood flow rate was measured by the internal jugular veins. A higher rate of venous outflow through internal jugular veins is associated with a more successful performance of the Luria test for verbal memory. A higher or lower blood flow rate affects the formation of neural networks of the brain. At a higher blood flow rate, the predominant areas of the resting neural networks (the passive mode network of the brain and the salient network) are localized in the frontal regions, at a low blood flow rate, the predominant neural network (frontal-parietal) is located in the left hemisphere. The state of faster and slower venous outflow forms neural networks using different neural formations that affect verbal memory. Reorganization of neural networks in this case, apparently, is the central mechanism responsible for cognitive decline in chronic cerebral ischemia (2 figs, 1 table, bibliography: 10 refs)

Vascular reactivity contributes to adipose tissue remodeling in obesity.

Vascular reactivity of adipose tissue (AT) is hypothesized to play an important role in the development of obesity. However, the exact role of vascular reactivity in the development of obesity remains unclear. In this study, we investigated the chronological changes in vascular reactivity and the microenvironments of the visceral AT (VAT) and subcutaneous AT (SAT) in lean and obese mice. Changes in blood flow levels induced by a β-adrenoceptor agonist (isoproterenol) were significantly lower in the VAT of the mice fed a high-fat diet (HFD) for 1 and 12 weeks than those in the VAT of the mice fed a low-fat diet (LFD) for the same period; no significant change was observed in the SAT of any mouse group, suggesting depot-specific vascular reactivity of AT. Moreover, the hypoxic area and the expression of genes associated with angiogenesis and macrophage recruitment were increased in the VAT (but not in the SAT) of mice fed an HFD for 1 week compared with mice fed an LFD. These changes occurred with no morphological changes, including those related to adipocyte size, AT vessel density, and the diameter and pericyte coverage of the endothelium, suggesting a determinant role of vascular reactivity in the type of AT remodeling. The suppression of vascular reactivity was accompanied by increased endothelin1 (Edn1) gene expression and extracellular matrix (ECM) stiffness only in the VAT, implying enhanced contractile activities of the vasculature and ECM. The results suggest a depot-specific role of vascular reactivity in AT remodeling during the development of obesity.

Physiologically Based Modeling of the Effect of Physiological and Anthropometric Variability on Indocyanine Green Based Liver Function Tests.

Accurate evaluation of liver function is a central task in hepatology. Dynamic liver function tests (DLFT) based on the time-dependent elimination of a test substance provide an important tool for such a functional assessment. These tests are used in the diagnosis and monitoring of liver disease as well as in the planning of hepatobiliary surgery. A key challenge in the evaluation of liver function with DLFTs is the large inter-individual variability. Indocyanine green (ICG) is a widely applied test compound used for the evaluation of liver function. After an intravenous administration, pharmacokinetic (PK) parameters are calculated from the plasma disappearance curve of ICG which provide an estimate of liver function. The hepatic elimination of ICG is affected by physiological factors such as hepatic blood flow or binding of ICG to plasma proteins, anthropometric factors such as body weight, age, and sex, or the protein amount of the organic anion-transporting polypeptide 1B3 (OATP1B3) mediating the hepatic uptake of ICG. Being able to account for and better understand these various sources of inter-individual variability would allow to improve the power of ICG based DLFTs and move toward an individualized evaluation of liver function. Within this work we systematically analyzed the effect of various factors on ICG elimination by the means of computational modeling. For the analysis, a recently developed and validated physiologically based pharmacokinetics (PBPK) model of ICG distribution and hepatic elimination was utilized. Key results are (i) a systematic analysis of the variability in ICG elimination due to hepatic blood flow, cardiac output, OATP1B3 abundance, liver volume, body weight and plasma bilirubin level; (ii) the evaluation of the inter-individual variability in ICG elimination via a large in silico cohort of n = 100,000 subjects based on the NHANES cohort with special focus on stratification by age, sex, and body weight; (iii) the evaluation of the effect of various degrees of cirrhosis on variability in ICG elimination. The presented results are an important step toward individualizing liver function tests by elucidating the effects of confounding physiological and anthropometric parameters in the evaluation of liver function via ICG.

Passive leg movement: A novel method to assess vascular function during passive leg heating?

Passive leg movement: A novel method to assess vascular function during passive leg heating?

A functional cerebral endothelium is necessary to protect against cognitive decline

A vascular insult occurring early in disease onset may initiate cognitive decline leading to dementia, while pharmacological and lifestyle interventions can prevent this progression. Mice with a selective, tamoxifen-inducible deletion of NF-κB essential modulator (Nemo) in brain endothelial cells were studied as a model of vascular cognitive impairment. Groups included NemoFl controls and three NemobeKO groups: One untreated, and two treated with simvastatin or exercise. Social preference and nesting were impaired in NemobeKO mice and were not countered by treatments. Cerebrovascular function was compromised in NemobeKO groups regardless of treatment, with decreased changes in sensory-evoked cerebral blood flow and total hemoglobin levels, and impaired endothelium-dependent vasodilation. NemobeKO mice had increased string vessel pathology, blood-brain barrier disruption, neuroinflammation, and reduced cortical somatostatin-containing interneurons. These alterations were reversed when endothelial function was recovered. Findings strongly suggest that damage to the cerebral endothelium can trigger pathologies associated with dementia and its functional integrity should be an effective target in future therapeutic efforts.

Neuroprotective Effects of Resveratrol in Ischemic Brain Injury

Cerebral ischemia represents the third cause of death and the first cause of disability in adults. This process results from decreasing cerebral blood flow levels as a result of the occlusion of a major cerebral artery. This restriction in blood supply generates low levels of oxygen and glucose, which leads to a decrease in the energy metabolism of the cell, producing inflammation, and finally, neurological deterioration. Currently, blood restoration of flow is the only effective approach as a therapy in terms of ischemic stroke. However, a significant number of patients still have a poor prognosis, probably owing to the increase in the generation of reactive oxygen species (ROS) during the reperfusion of damaged tissue. Oxidative stress and inflammation can be avoided by modulating mitochondrial function and have been identified as potential targets for the treatment of cerebral ischemia. In recent years, the beneficial actions of flavonoids and polyphenols against cerebrovascular diseases have been extensively investigated. The use of resveratrol (RSV) has been shown to markedly decrease brain damage caused by ischemia in numerous studies. According to in vitro and in vivo experiments, there is growing evidence that RSV is involved in several pathways, including cAMP/AMPK/SIRT1 regulation, JAK/ERK/STAT signaling pathway modulation, TLR4 signal transduction regulation, gut/brain axis modulation, GLUT3 up-regulation inhibition, neuronal autophagy activation, and de novo SUR1 expression inhibition. In this review, we summarize the recent outcomes based on the neuroprotective effect of RSV itself and RSV-loaded nanoparticles in vitro and in vivo models focusing on such mechanisms of action as well as describing the potential therapeutic strategies in which RSV plays an active role in cases of ischemic brain injury.

Stuttering: A Disorder of Energy Supply to Neurons?

Stuttering is a disorder characterized by intermittent loss of volitional control of speech movements. This hypothesis and theory article focuses on the proposal that stuttering may be related to an impairment of the energy supply to neurons. Findings from electroencephalography (EEG), brain imaging, genetics, and biochemistry are reviewed: (1) Analyses of the EEG spectra at rest have repeatedly reported reduced power in the beta band, which is compatible with indications of reduced metabolism. (2) Studies of the absolute level of regional cerebral blood flow (rCBF) show conflicting findings, with two studies reporting reduced rCBF in the frontal lobe, and two studies, based on a different method, reporting no group differences. This contradiction has not yet been resolved. (3) The pattern of reduction in the studies reporting reduced rCBF corresponds to the regional pattern of the glycolytic index (GI; Vaishnavi et al., 2010). High regional GI indicates high reliance on non-oxidative metabolism, i.e., glycolysis. (4) Variants of the gene ARNT2 have been associated with stuttering. This gene is primarily expressed in the brain, with a pattern roughly corresponding to the pattern of regional GI. A central function of the ARNT2 protein is to act as one part of a sensor system indicating low levels of oxygen in brain tissue and to activate appropriate responses, including activation of glycolysis. (5) It has been established that genes related to the functions of the lysosomes are implicated in some cases of stuttering. It is possible that these gene variants result in a reduced peak rate of energy supply to neurons. (6) Lastly, there are indications of interactions between the metabolic system and the dopamine system: for example, it is known that acute hypoxia results in an elevated tonic level of dopamine in the synapses. Will mild chronic limitations of energy supply also result in elevated levels of dopamine? The indications of such interaction effects suggest that the metabolic theory of stuttering should be explored in parallel with the exploration of the dopaminergic theory.

Zinc-containing Mohs' paste affects blood flow and angiogenesis suppression.

Mohs' paste, which is composed of zinc chloride and zinc oxide starch, is used for hemostasis of superficial malignancy in the clinical setting. We investigated the concentration of intramuscular zinc in mice after Mohs' paste application and evaluated its relationship with angiogenesis from the perspective of blood flow levels within 24h. Male C57BL/6JJmsSlc mice were administered single dose of Mohs' paste at 25%, 50%, and 75% after unilateral hind limb surgery, and glycerin, a viscosity modifier, was administered to the control group (0%). Hind limb blood flow levels were measured with a laser Doppler perfusion imaging system(n = 6). The amounts of intramuscular zinc and vascular endothelial growth factor-A (VEGF-A) expression were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) and western blotting, respectively (n = 5 or 3). Blood flow levels were significantly decreased in the 50% group after 8h, and significantly decreased in the 25% and 50% groups after 24h. Intramuscular zinc was significantly increased in the 50% and 75% groups after 8h. Western blotting showed that VEGF-A levels were significantly increased in the 25% and 50% groups after 8h. Based on analytical experiments and biological investigation, we predicated the pharmacological effect of Mohs' paste and found over 50% of it is critical in the blood flow and angiogenesis suppression after more than 8h of its application. The results suggest that the mechanism of blood flow suppression is independent of VEGF-A levels and might suppress future angiogenesis. Our findings support that of previous studies, in which Mohs' paste was expected to induce hemostasis and suppress angiogenesis. It is an excellent ointment that facilitates hemostasis by suppressing blood flow regardless of angiogenesis, and may be apt for situations where hemostasis is required in the clinical setting.

Trans-Ocular Brain Impedance Indices Predict Pressure Reactivity Index Changes in a Porcine Model of Hypotension and Cerebral Autoregulation Perturbation.

Cerebrovascular autoregulation (CA) is a protective mechanism that enables the cerebral vasculature to automodulate tone in response to changes in cerebral perfusion pressure to ensure constant levels of cerebral blood flow (CBF) and oxygen delivery. CA can be impaired after neurological injury and contributes to secondary brain injury. In this study, we report novel impedance indices using trans-ocular brain impedance (TOBI) during controlled systemic hemorrhage and hypotension to assess CA in comparison with pressure reactivity index (PRx). Yorkshire swine were instrumented to record intracranial pressure (ICP), mean arterial pressure (MAP), and CBF. TOBI was recorded using electrocardiographic electrodes placed on the closed eyelids. Impedance changes (dz) were recorded in response to introducing an alternating current (0.4mA) through the electrodes. MAP, ICP, and CBF were also measured. Animals were subjected to a controlled hemorrhage to remove 30-40% of each animal's total blood volume over 25-35min. Hemorrhage was titrated to reach an MAP of approximately 35mm Hg and end-tidal carbon dioxide above 28mm Hg. PRx was calculated as a moving Pearson correlation between MAP and ICP. TOBI indices were calculated as the amplitude of the respiratory-induced changes in dz. DZx was calculated as a moving Pearson correlation between dz and MAP. TOBI indices (dz and DZx) were compared with hemodynamic indicators and PRx. dz was shown to be highly correlated with MAP, ICP, cerebral perfusion pressure, and CBF (r = - 0.823, - 0.723, - 0.813, and - 0.726), respectively (p < 0.0001). During hemorrhage, cerebral perfusion pressure and CBF had a mean percent decrease (standard deviation) from baseline of - 54.2% (12.5%) and - 28.3% (14.7%), respectively, whereas dz increased by 277% (268%). Receiver operator characteristics and precision-recall curves demonstrated high predictive performance of DZx when compared with PRx with an area under the curve above 0.82 and 0.89 for receiver operator characteristic and precision-recall curves, respectively, with high sensitivity and positive predictive power. TOBI indices appear to track changes in PRx and hemodynamics that affect CA during hemorrhage-induced hypotension. TOBI may offer a suitable, less invasive surrogate to PRx for monitoring and assessing CA.

Transpulmonary thermodilution in patients treated with veno-venous extracorporeal membrane oxygenation

BackgroundWe tested the effect of different blood flow levels in the extracorporeal circuit on the measurements of cardiac stroke volume (SV), global end-diastolic volume index (GEDVI) and extravascular lung water index derived from transpulmonary thermodilution (TPTD) in 20 patients with severe acute respiratory distress syndrome (ARDS) treated with veno-venous extracorporeal membrane oxygenation (ECMO).MethodsComparative SV measurements with transesophageal echocardiography and TPTD were performed at least 5 times during the treatment of the patients. The data were interpreted with a Bland–Altman analysis corrected for repeated measurements. The interchangeability between both measurement modalities was calculated and the effects of extracorporeal blood flow on SV measurements with TPTD was analysed with a linear mixed effect model. GEDVI and EVLWI measurements were performed immediately before the termination of the ECMO therapy at a blood flow of 6 l/min, 4 l/min and 2 l/min and after the disconnection of the circuit in 7 patients.Results170 pairs of comparative SV measurements were analysed. Average difference between the two modalities (bias) was 0.28 ml with an upper level of agreement of 40 ml and a lower level of agreement of -39 ml within a 95% confidence interval and an overall interchangeability rate between TPTD and Echo of 64%. ECMO blood flow did not influence the mean bias between Echo and TPTD (0.03 ml per l/min of ECMO blood flow; p = 0.992; CI − 6.74 to 6.81). GEDVI measurement was not significantly influenced by the blood flow in the ECMO circuit, whereas EVLWI differed at a blood flow of 6 l/min compared to no ECMO flow (25.9 ± 10.1 vs. 11.0 ± 4.2 ml/kg, p = 0.0035).ConclusionsIrrespectively of an established ECMO therapy, comparative SV measurements with Echo and TPTD are not interchangeable.Such caveats also apply to the interpretation of EVLWI, especially with a high blood flow in the extracorporeal circulation. In such situations, the clinician should rely on other methods of evaluation of the amount of lung oedema with the haemodynamic situation, vasopressor support and cumulative fluid balance in mind.Trial registration: German Clinical Trials Register (DRKS00021050). Registered 03/30/2020https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017237

Influence of autologous bone marrow fraction and simvastatin on microcirculation of leg muscles in experimental critical ischemia of the lower limbs

Introduction. The effectiveness of cell therapy at the stage of critical limb ischemia is insufficient for regression of clinical manifestations of the ischemic process. Aim – to develop an experimental model of critical limb ischemia and to study the effect of the combined use of bone marrow autocells and simvastatin on the perfusion of ischemic tissues and the dynamics of the clinical picture of the ischemic process. Materials and methods. The experimental study was carried out on 180 male Wistar rats, divided into 6 groups of 30 animals each. In the first group (intact), the level of microcirculation in the muscles of the hind limb was determined. In the second group (sham-operated), the neurovascular bundle of the thigh was isolated and the wound was sutured with a continuous suture. In the third group, chronic critical ischemia of the leg muscles was modeled by removing the femoral, popliteal, anterior and posterior tibial arteries and veins, and damage to the peripheral nerve. In the fourth group, critical ischemia of the leg muscles was treated with simvastatin, in the fifth group – with the mononuclear fraction of autologous bone marrow, in the sixth one – with simvastatin and the mononuclear fraction of autologous bone marrow. The level of microcirculation in the leg muscles was determined using laser Doppler flowmetry LDF 100C and invasive needle sensor TSD144 on days 10, 21 and 28. Results. In the second group, a statistically insignificant decrease in the level of microcirculation was noted. In the third group, the level of regional blood flow in the ischemic muscle of the leg of rats on the 10th day was 2.5 times, on the 21st day – 1.7 times and on the 28th day 1.4 times less than in the group of intact animals. At the same time, in the fourth group after the administration of simvastatin to the animals, the regional blood flow increased 1.4; 1.5 and 1.5 times; in the fifth group, with the introduction of the mononuclear fraction of the bone marrow to animals at all periods, 1.6 times; in the sixth group after the combined administration of bone marrow cells and simvastatin – 2.0; 1.8 and 1.7 times. By the end of the experiment, in the animals of the fourth and fifth groups, it was possible to stop the progression of clinical manifestations, and in animals of the sixth group, their regression was achieved. Conclusion. The combined use of bone marrow cells and statins allows bringing the level of perfusion of ischemic tissues to normal and achieving regression of the clinical picture of the ischemic process by the end of the experiment.

Prediction of Intraoperative Fluorescence of Brain Gliomas: Correlation between Tumor Blood Flow and the Fluorescence.

Introduction: The prediction of the fluorescent effect of 5-aminolevulinic acid (5-ALA) in patients with diffuse gliomas can improve the selection of patients. The degree of enhancement of gliomas has been reported to predict 5-ALA fluorescence, while, at the same time, rarer cases of fluorescence have been described in non-enhancing gliomas. Perfusion studies, in particular arterial spin labeling perfusion, have demonstrated high efficiency in determining the degree of malignancy of brain gliomas and may be better for predicting fluorescence than contrast enhancement. The aim of the study was to investigate the relationship between tumor blood flow, measured by ASL, and intraoperative fluorescent glow of gliomas of different grades. Materials and methods: Tumoral blood flow was assessed in 75 patients by pCASL (pseudo-continuous arterial spin labeling) within 1 week prior to surgery. In all cases of tumor removal, 5-ALA had been administered preoperatively. Maximum values of tumoral blood flow (TBF max) were measured, and normalized tumor blood flow (nTBF) was calculated. Results: A total of 76% of patients had significant contrast enhancement, while 24% were non-enhancing. The histopathology revealed 17 WHO grade II gliomas, 12 WHO grade III gliomas and 46 glioblastomas. Overall, there was a relationship between the degree of intraoperative tumor fluorescence and ASL-TBF (Rs = 0.28, p = 0.02 or the TBF; Rs = 0.34, p = 0.003 for nTBF). Non-enhancing gliomas were fluorescent in 9/18 patients, with nTBF in fluorescent gliomas being 54.58 ± 32.34 mL/100 mg/s and in non-fluorescent gliomas being 52.99 ± 53.61 mL/100 g/s (p > 0.05). Enhancing gliomas were fluorescent in 53/57 patients, with nTBF being 170.17 ± 107.65 mL/100 g/s in fluorescent and 165.52 ± 141.71 in non-fluorescent gliomas (p > 0.05). Conclusion: Tumoral blood flow levels measured by non-contrast ASL perfusion method predict the fluorescence by 5-ALA; however, the additional value beyond contrast enhancement is not clear. ASL is, however, useful in cases with contraindication to contrast.

Post-exercise Body Cooling: Skin Blood Flow, Venous Pooling, and Orthostatic Intolerance.

Athletes and certain occupations (e.g., military, firefighters) must navigate unique heat challenges as they perform physical tasks during prolonged heat stress, at times while wearing protective clothing that hinders heat dissipation. Such environments and activities elicit physiological adjustments that prioritize thermoregulatory skin perfusion at the expense of arterial blood pressure and may result in decreases in cerebral blood flow. High levels of skin blood flow combined with an upright body position augment venous pooling and transcapillary fluid shifts in the lower extremities. Combined with sweat-driven reductions in plasma volume, these cardiovascular alterations result in levels of cardiac output that do not meet requirements for brain blood flow, which can lead to orthostatic intolerance and occasionally syncope. Skin surface cooling countermeasures appear to be a promising means of improving orthostatic tolerance via autonomic mechanisms. Increases in transduction of sympathetic activity into vascular resistance, and an increased baroreflex set-point have been shown to be induced by surface cooling implemented after passive heating and other arterial pressure challenges. Considering the further contribution of exercise thermogenesis to orthostatic intolerance risk, our goal in this review is to provide an overview of post-exercise cooling strategies as they are capable of improving autonomic control of the circulation to optimize orthostatic tolerance. We aim to synthesize both basic and applied physiology knowledge available regarding real-world application of cooling strategies to reduce the likelihood of experiencing symptomatic orthostatic intolerance after exercise in the heat.

Novel Hydrogen Sulfide (H2S)-Releasing BW-HS-101 and Its Non-H2S Releasing Derivative in Modulation of Microscopic and Molecular Parameters of Gastric Mucosal Barrier.

Hydrogen sulfide (H2S) is an endogenously produced molecule with anti-inflammatory and cytoprotective properties. We aimed to investigate for the first time if a novel, esterase-sensitive H2S-prodrug, BW-HS-101 with the ability to release H2S in a controllable manner, prevents gastric mucosa against acetylsalicylic acid-induced gastropathy on microscopic and molecular levels. Wistar rats were pretreated intragastrically with vehicle, BW-HS-101 (0.5–50 μmol/kg) or its analogue without the ability to release H2S, BW-iHS-101 prior to ASA administration (125 mg/kg, intragastrically). BW-HS-101 was administered alone or in combination with nitroarginine (L-NNA, 20 mg/kg, intraperitoneally) or zinc protoporphyrin IX (10 mg/kg, intraperitoneally). Gastroprotective effects of BW-HS-101 were additionally evaluated against necrotic damage induced by intragastrical administration of 75% ethanol. Gastric mucosal damage was assessed microscopically, and gastric blood flow was determined by laser flowmetry. Gastric mucosal DNA oxidation and PGE2 concentration were assessed by ELISA. Serum and/or gastric protein concentrations of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, VEGF, GM-CSF, IFN-γ, TNF-α, and EGF were determined by a microbeads/fluorescent-based multiplex assay. Changes in gastric mucosal iNOS, HMOX-1, SOCS3, IL1-R1, IL1-R2, TNF-R2, COX-1, and COX-2 mRNA were assessed by real-time PCR. BW-HS-101 or BW-iHS-101 applied at a dose of 50 μmol/kg protected gastric mucosa against ASA-induced gastric damage and prevented a decrease in the gastric blood flow level. H2S prodrug decreased DNA oxidation, systemic and gastric mucosal inflammation with accompanied upregulation of SOCS3, and EGF and HMOX-1 expression. Pharmacological inhibition of nitric oxide (NO) synthase but not carbon monoxide (CO)/heme oxygenase (HMOX) activity by L-NNA or ZnPP, respectively, reversed the gastroprotective effect of BW-HS-101. BW-HS-101 also protected against ethanol-induced gastric injury formation. We conclude that BW-HS-101, due to its ability to release H2S in a controllable manner, prevents gastric mucosa against drugs-induced gastropathy, inflammation and DNA oxidation, and upregulate gastric microcirculation. Gastroprotective effects of this H2S prodrug involves endogenous NO but not CO activity and could be mediated by cytoprotective and anti-inflammatory SOCS3 and EGF pathways.

A Portable Multicontrast Microscope for Multiscale Imaging of the Microcirculation

Objective To develop a portable microscope capable of interrogating the microcirculation in vivo with multiple contrasts over multiple spatial scales. Methods We used state-of-the-art 3D printing and optics design techniques to fabricate a miniature microscope the size of a US quarter (Fig. 1 a, b)1. It weights 9g and acquires images via three optical contrasts: intrinsic optical signals (IOS)2, laser speckle contrast (LSC)3 and fluorescence (FL). The IOS channel, which relies on light absorption by red blood cell (RBC) bound hemoglobin (HbT), can be used to visualize microvascular morphology, while the LSC channel enables observing blood flow levels by using the orderly flow of RBCs along vessels as a contrast agent. The FL channel can be used for arterio-venous discrimination via the arrival times of an intravenously (iv) injected fluorescent dye (e.g. FITC-Dextran, 70 kDa). The microscope can acquire images at 15 frames per second over a 3x3 mm2 field of view (FoV) at 5 µm resolution. We also designed an adaptor which enhances the resolution tenfold to 0.5 µm. It is operated via USB connections to a laptop, and is portable (Fig. 1c), making it convenient for imaging the microcirculation in a range of preclinical applications. Results We demonstrated the utility of our microscope by using it to interrogate the structure and function of the murine brain and ear microcirculation at different spatial scales. Figs. 1d, e show maps of microvascular morphology and blood flow in a portion of the murine brain under ketamine anesthesia at 5 µm resolution. Fig. 1f shows the map of arrival times of the iv injected fluorescent dye. Dark blue regions corresponding to arrival times less than 0.5 s were used to identify arteries. Figs. 1g, h show plots of changes in HbT (i.e. cerebral blood volume) and cerebral blood flow (CBF) corresponding to an artery and vein (boxes marked “A” and “V” in Fig. 1d) over 3 hours while the animal recovers from anesthesia. Here, the arterial and venous time courses illustrate contrasting flow-volume relationships that indicate the varying systemic effects of anesthesia on components of the microcirculation. Fig 2a shows the microscope with its high-magnification adaptor, while Fig. 2b illustrates the exquisite microvascular details revealed with the adaptor in contrast to images acquired without it. Here, the FL channel was used in conjunction with an iv injected dye to enhance microvascular contrast. One could also “stitch” together these high-resolution images to create a mosaic with wider coverage (Fig. 2c). Since individual RBCs were discernable in these high-resolution images (Fig. 2d), we successfully employed RBC tracking to characterize cellular-scale flow dynamics within the microcirculation (Fig. 2e). Conclusion The multicontrast and multiscale imaging capabilities of our microscope will enable investigators to comprehensively interrogate the structure and function of microcirculation in diverse organ sites and preclinical disease models. Its design and portability enables imaging of unanesthetized animals, convenient usage, and fosters collaborations.

Influence of Inosine on Cerebral Hemodynamics in Space Motion Sickness in Experimental Animals.

Motion sickness occurs worldwide in healthy individuals regardless of age, ethnicity, or gender. It is an acute disorder; it can also present as a chronic disorder in some individuals. Motion sickness not only includes vomiting and nausea, but also includes other features such as pallor of varying degrees, cold sweating, headache, drowsiness, increased salivation, and cranial pain, which are severe. Some of the other assessment scales can interpret sickness on exposure to virtual or visual stimulation and while travelling in different types of transport. The aim of our research is to study the effect of the drug on the level of blood flow and vascular reactivity of cerebral vessels when simulating changes in the cerebral circulation in terrestrial conditions characteristic of hypogravity. Chronic experiments were performed on non-anesthetized rabbits with large hemispheres, thalamus and hypothalamus were implanted with the needle-platinum electrodes 150 mm in diameter in the cortex, and local blood flow and vascular reactivity were recorded accordingly. Cerebrovascular disturbances were modeled using an MSAOP (motion sickness of animals in the anti-orthostatic position) with an inclined angle of 45° for 2 hours. Local blood flow (BF) was measured in ml/min/100g of tissue by the method of registration of hydrogen clearance. The vasodilator coefficient of reactivity (CrCO2) was calculated by the ratio of BF against the background of inhalation of a mixture of 7% CO2 with air to the initial BF; vasoconstrictor - in relation to BF on the background of inhalation of 100% O2 to the initial BF (CrO2). A series of experiments were carried out with different routes of drug administration: First, inosine was administered intravenously at a dose of 5 mg/kg immediately before the start of SMS modeling, same dose was administered 30 minutes before the start of exposure. As a control, we used the results of experimental animals under similar conditions without the administration of the drugs. Inosine has pronounced protective properties in cerebrovascular disorders on the background of space motion sickness (SMS) modeling, which is manifested by normalization of BF and restoration of compensatory reactions of cerebral vessels. In the mechanism of cerebroprotective action of inosine, it is able to correct the metabolic processes, which play an important role and help increase the compensatory capabilities and functional stability of the cerebrovascular system under gravitational influences. When using inosine orally, the effects are more pronounced than when administered intravenously, which should be taken into account when using it for the prevention of cerebrovascular disorders in extreme conditions.

Flow manipulation and the association with myocardial contractility during extracorporeal life support (FLAME)

Abstract Funding Acknowledgements Type of funding sources: None. Background Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is an advanced technique in extracorporeal life support (ECLS) used to support extreme circulatory failure including patients with cardiac arrest and cardiogenic shock refractory to conventional support. It is a long-standing belief that peripheral V-A ECMO poses increased afterload to the inured heart, but conventional echocardiographic measurements are often insensitive in detecting subtle changes in loading conditions. Purpose This study aimed to evaluate the effects of varying blood flow during peripheral V-A ECMO on intrinsic myocardial contractility, using detailed echocardiographic assessment including speckle tracking echocardiography (STE). Methods Adult patients with acute cardiogenic shock who were supported by peripheral V-A ECMO from April 2019 to September 2020 were recruited. Serial hemodynamic and cardiac performance parameters were measured by transthoracic echocardiogram (TTE) within 48 hours after implementation of V-A ECMO, at different levels of extracorporeal blood flow – 100%, 120% and 50% of target blood flow (TBF). Results A total of 30 patients were included. 22 (71%) were male, and the mean (SD) age was 54 (13) years. The major indications for V-A ECMO were myocardial infarction (19, 63% patients), and myocarditis (5, 17%). With a decrease in extracorporeal blood flow from 100% to 50% of TBF, mean arterial pressure (MAP) dropped from 76+/-3 to 64+/-3mmHg (p &amp;lt;0.001), and cardiac index (CI) increased from 0.89+/-0.13 to 1.27+/-0.18L/min/m2 (p &amp;lt; 0.001). All indices of left ventricular contractility improved at a lower extracorporeal blood flow: the myocardial contractility measured by global longitudinal peak systolic strain (GLPSS) improved from -3+/-0.7% to -5+/-0.8% (p &amp;lt; 0.001); left ventricular ejection fraction (LVEF) increased from 21.5+/-2.6% to 30.9+/-2.7% (p &amp;lt; 0.001) and 19.7+/-3.1% to 28.4+/-3.2% (p &amp;lt; 0.001) by biplane and linear methods, respectively; left ventricular index of myocardial performance (LIMP) improved from 1.51+/-0.12 to 1.03+/-0.09 (p &amp;lt; 0.001). Similar findings were reproduced when comparing left ventricular contractility at extracorporeal blood flows of 120% and 50% of TBF. Conclusions The ECMO blood flow rate in peripheral V-A ECMO is inversely related to myocardial contractility, and is quantifiable by myocardial strain measured by STE.

Concentrations of estradiol, progesterone and testosterone in serum and cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage correlate weakly with transcranial Doppler flow velocities

BackgroundThe implication of the steroids estradiol, progesterone and testosterone in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) has not been comprehensively assessed. In rodents, studies suggested beneficial effects of steroids on cerebral vasospasm after experimental SAH. Studies in humans are warranted, however, a general dilemma of human studies on neuroactive substances is that the brain is not directly accessible and that concentrations in the periphery may not adequately parallel concentrations in the central compartments. In the present study, concentrations of estradiol, progesterone and testosterone in serum and cerebrospinal fluid (CSF) of patients with aSAH were determined. Blood flow velocities in cerebral arteries were measured by transcranial Doppler sonography (TCD). The aim of this study was to evaluate the correlations between the cerebral blood flow velocities and levels of estradiol, progesterone and testosterone in CSF and serum.ResultsSamples of serum and CSF of 42 patients with aSAH were collected concomitantly daily or every other day via the arterial line and the external ventricular drainage for two weeks after the hemorrhage. Blood flow velocities in the cerebral arteries were determined by TCD. Total estradiol, progesterone and testosterone concentrations were measured by electro-chemiluminescence immunoassay. The strength of correlation was assessed by Spearman’s rank correlation coefficient. The correlation analysis revealed very weak correlations between cerebral blood flow velocities and concentrations of estradiol, progesterone and testosterone levels in both compartments with correlation coefficients below 0.2.ConclusionsIn humans with aSAH, merely very weak correlations between flow velocities in cerebral arteries and concentrations of estradiol, progesterone and testosterone in serum and CSF were demonstrated. These results suggest a limited influence of the respective steroids on cerebral vascular tone although vasodilatory effects were described in rodent studies. Thus, the implication of steroids in processes of neurological deterioration warrants further clarification.