Arteriolar Blood Flow Research Articles

An Alternative Photothrombotic Model of Transient Ischemic Attack.

Animal models mimicking human transient ischemic attack (TIA) and cerebral microinfarcts are essential tools for studying their pathogenetic mechanisms and finding methods of their treatment. Despite its advantages, the model of single arteriole photothrombosis requires complex experimental equipment and highly invasive surgery, which may affect the results of further studies. Hence, to achieve high translational potential, we focused on developing a TIA model based on photothrombosis of arterioles to combine good reproducibility and low invasiveness. For the first time, noninvasive laser speckle contrast imaging (LSCI) was used to monitor blood flow in cerebral arterioles and reperfusion was achieved. We demonstrate that irradiation of mouse cerebral cortical arterioles using a 532-nm laser with a 1-mm-wide beam at 2.4 or 3.7 mW for 55 or 40 s, respectively, after 15 mg/kg intravenous Rose Bengal administration, induces similar ischemia-reperfusion lesions resulting in microinfarct formation. The model can be used to study the pathogenesis of spontaneously developing cerebral microinfarcts in neurodegeneration. Reducing the exposure times by 10 s while maintaining the same other parameters caused photothrombosis of the arteriole with reperfusion in less than 1 h. This mode of photodynamic exposure caused cellular and subcellular level ischemic changes in neurons and promoted the activation of astrocytes and microglia in the first day after irradiation, but not later, without the formation of microinfarcts. This mode of photodynamic exposure most accurately reproduced human TIA, characterized by the absence of microinfarcts.

Novel in vivo optogenetic tools reveal autonomous pacemaker control of renal hemodynamics by macula densa cells

Macula densa (MD) cells, the tubular component of the juxtaglomerular apparatus (JGA) are generally considered as sensor cells detecting tubular salt (NaCl) concentration and based on this information provide feedback control of glomerular hemodynamics (tubuloglomerular feedback, TGF). However, the neuron-like differentiation and activity as non-traditional MD functions are emerging. This study addressed the paradigm-shifting hypothesis that rather than being simply the sensory arm of TGF, MD cells function as the nephron’s autonomous pacemaker and the primary driver and oscillator of glomerular hemodynamics. Single cell MD Ca2+ signaling was analyzed in vivo using intravital multiphoton microscopy (MPM) of MD-GT mice that selectively express the ratiometric Ca2+ reporter GCaMP6f/tdTomato in MD cells. Optogenetic MD stimulation was induced in vivo by blue light (470nm) exposure of MD-Ai27 mouse kidneys that express the depolarizing channelrhodopsin ChR2 specifically in MD cells. Conversely, MD inhibition was induced by yellow light (560nm) exposure of MD-Ai39 mouse kidneys that selectively express the hyperpolarizing halorhodopsin NpHR in MD cells. Cell membrane expression of ChR2 (in MD-Ai27 mice) and NpHR (in MD-Ai39 mice) only in the MD among all renal cell types was confirmed using immunohistochemistry. Pacemaker-like regular Ca2+ oscillations (4-fold elevations in baseline Ca2+ and average frequency of 0.03 Hz) and their cell-to-cell propagation within the MD plaque via long cell processes were observed in MD-GT mice. These Ca2+ oscillations were MD cell autonomous, as they were preserved in freshly dissected single MD cells and in the in vitro dissected and microperfused JGA, and were exclusively confined to the MD area. Bulk and scRNA seq and MD transcriptome analysis identified the high MD expression of genes related to pacemaker function, cell membrane depolarization, voltage-dependent ion channels, Ca2+ signaling and synaptic transmission that was validated by immunohistochemistry. Blue light exposure of single glomeruli/JGAs using ROI scan in MD-Ai27 mouse kidneys that previously underwent superficial corticotomy (open loop nephrons) acutely and reversibly increased capillary and afferent (AA)/efferent arteriole (EA) blood flow by approx. 50% in the light-exposed glomerulus but not in adjacent glomeruli. In contrast, yellow light exposure of single glomeruli/JGAs in MD-Ai39 mouse kidneys acutely and reversibly decreased blood flow but increased glomerular capillary diameter (suggesting preferential EA vs AA vasoconstriction) in the exposed but not in adjacent single nephrons. In addition, yellow light stimulation of single glomeruli in MD-Ai39 mouse kidneys augmented the spontaneous glomerular blood flow oscillations in these open-loop nephrons (frequency of 0.03 Hz), but not in adjacent control nephrons. Altogether, these studies identified MD cells as the nephron’s central pacemaker and oscillator of single nephron blood flow, and emphasized the importance of MD cell membrane potential and Ca2+-dependent vasodilator release as a major driver of nephron function. DK064234 DK123564 DK135290. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Numerical analysis of blood flow through stenosed microvessels using a multi-phase model

Blood flow in arterioles have attracted considerable research attention due to their clinical implications. However, the fluid structure interaction between red blood cells and plasma in the blood poses formidable difficulty to the computational efforts. In this contribution, we seek to represent the red blood cells in the blood as a continuous non-Newtonian phase and construct a multi-phase model for the blood flow in microvessels. The methods are presented and validated using a channel with sudden expansion. And the resulting blood flow inside a stenosed microvessel is investigated at different inlet velocity amplitudes and hematocrits. It is show that the increase of both inlet velocity amplitude and inlet hematocrit leads to longer and thicker cell-rich layer downstream the stenosis. Besides, it is found that the maximum values of wall shear stress scales up with inlet velocity amplitudes and hematocrits. These results show the validity of the proposed computational model and provide helpful insights into blood flow behaviors inside stenosed vessels.

МИКРОЦИРКУЛЯЦИЯ (ЧАСТЬ 1 – ГЛАВНЫЕ ДЕЙСТВУЮЩИЕ «ЛИЦА» И ИХ РОЛЬ В СИСТЕМЕ КРОВООБРАЩЕНИЯ)

The article presents modern views on microcirculation, which is the terminal compartment of the cardiovascular system, built into the tissue structure and determining the target function of blood circulation – the exchange between blood and tissues of substrates, energy and information, which ensures the maintenance of life support processes at the cellular level. The paper highlights the hemodynamic features that determine the main functions of microcirculatory vessels as the most important part of the blood circulation. The structure and morphofunctional features of all levels of microcirculation including the smallest vessels of the terminal bed, which preserve the morphological structure of arteries and veins, are described in detail. The main mechanisms of regulation of arteriolar blood flow are identified: neurohumoral, myogenic, and metabolic. A detailed description of the endothelium is given. The role of the barrier function of the endothelium in maintaining the balance between osmotic and hydrostatic pressure and in the formation of the lymphatic system for drainage of excess interstitial fluid has been noted. The results of studies on microvascular endothelial cells, in which genes encoding basement membrane proteins are especially active, are presented. Attention is focused on the morphological and functional properties of the endothelial cell glycocalyx as a new clinical paradigm. The glycocalyx is present in all capillaries, arteries and veins and is a structure of distant interaction of endothelial cells with their environment, changing under pathological conditions (adhesion, thrombus formation, apoptosis).

High-molecular-weight linear polymers improve microvascular perfusion after extracorporeal circulation.

High-molecular-weight linear polymers (HMWLPs) have earned the name "drag-reducing polymers" because of their ability to reduce drag in turbulent flows. Recently, these polymers have become popular in bioengineering applications. This study investigated whether the addition of HMWLP in a venoarterial extracorporeal circulation (ECC) model could improve microvascular perfusion and oxygenation. Golden Syrian hamsters were instrumented with a dorsal skinfold window chamber and subjected to ECC using a circuit comprised of a peristaltic pump and a bubble trap. The circuit was primed with lactated Ringer solution (LR) containing either 5 ppm of polyethylene glycol (PEG) with a low molecular weight of 500 kDa (PEG500k) or 5 ppm of PEG with a high molecular weight of 3,500 kDa (PEG3500k). After 90 min of ECC at 15% of the animal's cardiac output, the results showed that the addition of PEG3500k to LR improved microvascular blood flow in arterioles and venules acutely (2 h after ECC), whereas functional capillary density showed improvement up to 24 h after ECC. Similarly, PEG3500k improved venular hemoglobin O2 saturation on the following day after ECC. The serum and various excised organs all displayed reduced inflammation with the addition of PEG3500k, and several of these organs also had a reduction in markers of damage with the HMWLPs compared to LR alone. These promising results suggest that the addition of small amounts of PEG3500k can help mitigate the loss of microcirculatory function and reduce the inflammatory response from ECC procedures.NEW & NOTEWORTHY High-molecular-weight linear polymers have gained traction in bioengineering applications. The addition of PEG3500k to lactated Ringer solution (LR) improved microvascular blood flow in arterioles and venules acutely after extracorporeal circulation (ECC) in a hamster model and improved functional capillary density up to 24 h after ECC. PEG3500k improved venular hemoglobin O2 saturation and oxygen delivery acutely after ECC and reduced inflammation in various organs compared to LR alone.

Beneficial effects of clazosentan add-on treatment on delayed cerebral microcirculatory disturbances after aneurysmal subarachnoid hemorrhage

ObjectiveThis retrospective study aimed to analyze the prospectively collected data of computed tomography (CT) perfusion imaging and to examine if clazosentan add-on administration prevented post-subarachnoid hemorrhage (SAH) delayed cerebral microcirculatory dysfunctions. MethodsA total of 36 consecutive patients with non-mild SAH due to ruptured anterior circulation aneurysms and no significant cardiopulmonary dysfunctions (mean age, 67.9 years; and admission World Federation of Neurological Surgeons grades IV–V, 66.7 %) underwent aneurysmal obliteration up to day 3 post-SAH, followed by our conventional treatment (fasudil hydrochloride, cilostazol and perampanel administrations; n = 20; January 2020 to May 2022) or add-on administration of clazosentan (10 mg/hr) to the conventional treatment (n = 16; June 2022 to May 2023). ResultsClazosentan add-on treatment significantly affected perioperative fluid management, which appeared to have no effects on the finding of CT perfusion imaging performed a median of 6.5 to 7.0 days post-SAH. However, cerebral blood flow and mean transit time were better in patients receiving add-on administration of clazosentan, although angiographic vasospasm frequencies and cerebral blood volume values were similar between the two treatment groups. ConclusionThe findings suggest that clazosentan add-on treatment has beneficial effects against post-SAH angiographic vasospasm-unrelated delayed cerebral microcirculatory dysfunctions possibly by improving blood flow in smaller resistance arteries or arterioles.

Activation of transient receptor potential channels is involved in reactive oxygen species (ROS)-dependent regulation of blood flow by (-)-epicatechin tetramer cinnamtannin A2

Intervention trials confirmed that blood flow-mediated dilatation increases significantly after intake of astringent (-)-epicatechin (EC) oligomers (procyanidins)-rich foods, but the mechanism remains unclear. We have previously found that procyanidins can activate the sympathetic nervous and subsequently increase blood flow. Here, we examined whether procyanidin-derived reactive oxygen species (ROS) activate transient receptor potential (TRP) channels in gastrointestinal sensory nerves and consequently induce sympathoexcitation. We evaluated the redox properties of EC and its tetramer cinntamtannin A2 (A2) at pH 5 or 7, mimicking plant vacuole or oral cavity/small intestine using a luminescent probe. At pH 5, A2 or EC showed O2·- scavenging ability, but they promoted O2·- generation at pH 7. We observed blood flow in rat cremaster arterioles using laser Doppler, a single oral dose of 10 µg/kg A2 markedly increased blood flow, while EC showed little activity. This change with A2 was significantly dampened by co-administration of adrenaline blocker, ROS scavenger N-acetyl-L-cysteine (NAC), TRP vanilloid 1, or ankyrin 1 antagonist. We also performed a docking simulation of EC or A2 with the binding site of a typical ligand for each TRP channel and calculated the respective binding affinities. The binding energies were notably higher for A2 than typical ligands, suggesting that A2 is less likely to bind to these sites. ROS produced at neutral pH following the orally administered A2 to the gastrointestinal tract could activate TRP channels, triggering sympathetic hyperactivation and causing hemodynamic changes.

A model for upstream signalling in the control of capillary blood flow

Blood supply to tissues is controlled through vasoconstriction and vasodilation activated by components of the vascular wall and smooth muscle cells. Local oxygen saturation and wall shear stress play an important role in this process and wall shear stress has a role in capillary and venular flow as well as flow in arterioles and arteries. Local capillary networks can dilate to increase flow but there is little clear evidence of how local capillary networks act to increase arteriolar blood flow when needed. Pulsatile flow plays an important part in signalling wall shear stress within the vascular system and it has recently been shown that pulse pressure changes can be efficiently transmitted along soft walled fluid filled tubes such as blood vessels. This confirms that pulse pressure within the system can maintain downstream flow; it also raises the question of whether pulse pressure changes can signal upstream from local capillary beds to the supplying arteriole.

Microvascular changes in young hamsters after single heterochronic blood transfusion of one unit of blood

Aging is the most significant risk factor for many chronic diseases. Studies of heterochronic blood exchange show that blood and plasma from old-age animals have senescent effects in young mice. However, the underlying mechanisms of how bloodborne factors promote aging remain largely unknown, and studies of blood transfusions' effects on donors of different ages are currently unavailable. This study aimed to compare the microcirculatory effects of blood transfusions from young or old donors in anemic young animals. Blood was collected from anesthetized young (8 weeks old) and older (52-60 weeks old) golden Syrian hamsters via cardiac puncture into CP2D (from an AS-3 blood preparation kit). The supernatant and buffy coat were removed. The AS-3 additive was added according to manufacture instructions, and packed red cells were mixed gently. For microhemodynamic studies, young golden Syrian hamsters instrumented with a dorsal window chamber were subjected to an isovolemic hemodilution of 30% of the animal's blood volume with 5% human serum albumin to induce a normovolemic anemic state. The next day, the anemic animals were randomly assigned to young or older blood and received a transfusion of a volume equivalent to a single unit of red cells. The microhemodynamics in arterioles lower and greater than 60 μm and venules between 20 and 80 μm and functional capillary density (FCD) were measured. Hemodilution acutely reduced hematocrit (Hct) to 60% of the baseline and increased microvascular blood flow in venules and arterioles while decreasing the FCD. Transfusion of young or old donors’ blood increased the Hct. There was no significant change post-transfusion in the diameter or the flow of the arterioles in the young donors' blood group compared to old donors’ blood. The animals transfused with blood from young donors restored venules flow and diameter similarly to baseline (pre-anemia). However, the old donors’ blood group did not show the same recovery. More importantly, the FCD significantly improved after younger donors' blood transfusions compared to the old ones. These results suggest that recovery from anemia is improved when using blood from younger donors, as this ensures higher FCD and supports proper tissue homeostasis. This study intentionally tried to recapitulate how blood is processed in the USA and transfuse only a conservative amount of blood into anemic animals. Studies have shown that heterochronic parabiosis (surgically joining younger and older animals in which blood, organs, and environments are shared) or a blood exchange rejuvenates old tissues. Here using a heterochronic blood transfusion, we show that the donor's age determines the recovery of FCD after transfusion. These deficits could be due to capillary collapse preventing oxygen from arriving uniformly through the tissue, as the FCD determines the microvascular oxygen diffusion field. Future studies will look at the implication of the recovery of FCD after transfusion. This study was supported by National Institutes of Health grants R01HL162120, R01HL159862 and the Department of Defense under grants W81XWH1810059. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of type 1 diabetes and its duration on wall-to-lumen ratio and blood flow in retinal arterioles.

Subclinical damage to both the small and large vessels may contribute to the development and progression of cardiovascular disease. Scanning laser Doppler flowmetry (SLDF), an established method used to measure retinal microcirculation, has been successfully applied in hypertensive and post-stroke patients. Retinal microcirculation was assessed in 158 patients with type 1 diabetes and 38 age-matched healthy controls. The diabetics were divided into 3 groups: group A with diabetes duration <12months, group B with diabetes with 1-10years, and group C >10years of diabetes. Retinal capillary structure and perfusion were evaluated using a Heidelberg retina flowmeter and automatically analyzed with full-field perfusion imaging. Age and BMI were comparable in all the diabetic patients and the controls (mean age 24.8±4.7years, mean BMI 22.9±4.1). In the univariate analyses, RCF (retinal capillary flow) was significantly higher in group A (297±121 arbitrary units [AU]) vs group B (236±52AU; p=0.007) and group C (236±70AU; p=0.008) and comparable to that of the controls (p=0.46). Additionally, the WLR (Wall-to-Lumen Ratio) was highest in group C compared to the other diabetic subgroups and controls (p=0.001). Multivariate regression analyses including age, BMI, sex, HbA1c, smoking, systolic blood pressure, and diabetes duration as covariates, showed, that only diabetes duration was significantly associated with WLR variations, whereas HbA1c was significantly linked to retinal capillary flow levels. New-onset diabetes is associated with an increase in RCF, which then gradually decreased with the duration of the disease. Structural changes of the retinal arterioles estimated via WLR are evident later in the course of diabetes, especially when the disease duration exceeded 10years.

A Pilot Study Assessing Retinal Blood Flow Dysregulation in Glaucoma Using Erythrocyte Mediated Velocimetry.

The purpose of this study was to compare autoregulation of retinal arteriolar and venular blood flow in patients with glaucoma, glaucoma suspect participants, and control participants using erythrocyte mediated velocimetry. This prospective cohort pilot study included 7 eyes of 5 participants with glaucoma, 15 eyes of 8 glaucoma suspect participants, and 11 eyes of 6 control participants. Mean erythrocyte velocity in retinal arterioles and venules was measured using erythrocyte mediated velocimetry at room air and after oxygen supplementation. Change in erythrocyte velocity was compared among all groups using generalized estimating equations. In total, 64 vessels (18 with glaucoma, 31 that were glaucoma suspect, and 15 controls) of 33 eyes of 19 participants were analyzed. There was no significant difference in baseline velocities in arterioles or venules among the three groups. With induction of hyperoxia, mean arterial erythrocyte velocity decreased in glaucoma (-7.2 ± 13.7%), which differed from controls and glaucoma suspects where erythrocyte velocity increased with hyperoxia by 4.6 ± 13.3% (P = 0.002) and 7.2 ± 21.7% (P = 0.03), respectively. A higher baseline arteriolar velocity (β = -3.9% per mm/s, P = 0.002), glaucoma diagnosis (β = -21.1%, P = 0.03), and White race (β = -20.0%, P = 0.01) were associated with decreased velocity in response to arterial hyperoxia. Hyperoxia increased erythrocyte velocity in control and glaucoma suspect participants, but decreased erythrocyte velocity in glaucoma participants, possibly due to impaired autoregulation. Baseline velocity, glaucoma diagnosis, and White race were associated with a decrease in velocity with induction of hyperoxia. The European Medicines Agency (EMA) permits precision measurements of blood flow which may aid in the development of biomarkers of glaucoma-related dysregulation of blood flow.

Apohemoglobin-Haptoglobin Complex Prevents Microvascular Dysfunction in Sickle Cell Mice: Potential Therapeutic Approach for Vaso-Occlusive Crisis

Background: Sickle cell disease (SCD) is associated with episodes of vaso-occlusive events (VOE) caused by the effects of hemoglobin S (HbS) polymerization in red blood cells (RBCs) and resultant hemolysis. In the acute setting, treatment for VOE is limited to supportive care such as hydration and aggressive pain management as no specific therapies can alter the course of acute VOE. The apohemoglobin-haptoglobin (apoHb-Hp) complex is a two-protein formulation that is capable of scavenging and neutralizing the toxic effects of cell-free hemoglobin (Hb) and heme released from the hemolysis of polymerized HbS RBCs. The primary objective of this study was to evaluate the microcirculatory effects of apoHb-Hp during hypoxia-induced VOE. Methods: The effects of apoHb-hp was studied in a mouse model of SCD using sickle cell transgenic mice (HbSS-Towne's mice, and compared to mice expressing normal human Hb (HbAA-Towne's mice). Each group consisted of 11 mice, they were initially kept in normal conditions (21% O2) for an hour followed by a hypoxic state (7% O2) for another hour and finally brought back to normal conditions (21% O2) for an hour before being sacrificed. ApoHb-hp (60 mg/mL) and Hp (85 mg/mL) were injected intravenously to yield equimolar total heme and Hb binding capacity between treatments prior to hypoxia exposure. During baseline, hypoxia and normoxia systemic parameters (mean arteriole pressure and heart rate), blood gases (pO2,A, pO2,v, sO2,A, sO2,v), hematological properties (total Hb concentration, hematocrit, and concentration of lactate) and microcirculatory hemodynamics (velocity, diameter, flow and functional capillary density) were measured. After the mice were sacrificed a count of present macrophages, neutrophils and lymphocytes were quantified in the pulmonary tissue. Results: There was no notable changes in blood gas concentrations with any of the treatments. ApoHb-Hp treatment improved microcirculatory hemodynamics of HbSS mice by preventing hypoxia-induced vasoconstriction and reduction of blood flow in arterioles <40µm (P=0.818, P<0.0001), arterioles >40 µm (P>0.9999, P<0.0001) and venules 20<x<60 µm (P=0.150, P=0.330) compared to HbAA mice. Furthermore, the functional capillary density saw favorable recovery to baseline when HbSS mice were treated with apoHb-Hp seeing a 36% drop initially, 50% drop after 24 hours, 35% drop after 48 hours, and 27% drop after 72 hours. For comparison, HbSS mice that didn't receive treatment saw a 50% drop initially, 77% drop after 24 hours, 80% drop after 48 hours, and 72% drop after 72 hours when compared to baseline. Conclusion: These results suggest a role for ApoHb-Hp complex in alleviating microvascular changes occurring during hypoxia mediated acute vaso-occlusion in SCD and merits further study for development as a potential therapeutic. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Study of Effect of Different Shapes of Nanoparticles in Three-Layer Model for Blood Flow in Arterioles

Arterioles are pivotal console of hemodynamics as they are significant contributors to pressure. Under various physiological conditions like administration of a drug, arterioles ascertain divergent mechanical forces. The current communication discusses the effect of different shapes of copper nanoparticles inoculated as nano drugs in arterioles. The blood is assumed to be a non-Newtonian fluid and is delineated as nanofluids. The three-layer model is used for modeling the blood flow as it aptly describes the flow of blood in narrow vessels of diameter less than 100 μm. The Hamilton-Crosser model is implemented to describe the thermal conductivity of nanofluid as this model holds in accordance with experimental as well as theoretical results. The expressions are also obtained for density, thermal expansion and viscosity of the considered nanofluid. The equations are solved analytically and graphs have been plotted using MATLAB. The relative consequence of various shapes of nanoparticles like platelets, blades, cylinders and bricks is observed in temperature, velocity and flow rate. It has been investigated through the graphs that brick-shaped nanoparticles have shown a maximum rise in temperature, velocity and flow rate. And reverse results are observed for blade-shaped nanoparticles. The effect of volume fraction, heat source parameter and Grashof number have also been inspected. The considered analysis shows that a suitable shape of nanoparticle can be used to develop the nano drug according to biomedical needs.

Drag Reducing Polymers Improves Microvascular Perfusion After Extracorporeal Circulation

Drag reducing polymers (DRPs) have been used in various engineering applications, such as the transfer of crude oil or seawater in pipelines. The use of DRPs has crossed into the bioengineering sphere, with previous ex‐vivo and in‐vivo studies suggesting that the addition of DRPs decreases the erythrocyte cell free layer (CFL) or cell depleted layer near the vessel wall and increases microvascular blood flow. The objective of this study was to investigate whether the addition of DRPs would improve microvascular perfusion in a rodent model of extracorporeal circulation (ECC).Male Golden Syrian hamsters were instrumented with a dorsal skinfold window chamber, along with an arterial catheter into the right carotid artery to monitor blood pressure and heart rate. During ECC, animals were anesthetized with isoflurane, and a drainage cannula was inserted through the left jugular. The animal was connected to the circuit, primed with either lactate ringers (LR group) or 5 PPM 500 kDa polyethylene glycol in lactate ringers (DRP group). Blood was drained from the jugular cannula, run through a peristaltic pump and bubble trap, before entering the carotid catheter for reinfusion. The circuit was run for 90 minutes in total, with 60 minutes at a flowrate equivalent to 15% of the animal’s cardiac output. Measurements were taken before ECC (baseline, BL) and after 1, 2, and 24 hrs post‐ECC. At each timepoint, microvessel (arterioles and venules) diameter, red blood cell velocity and functional capillary density (FCD) were measured using intravital microscopy.Arteriole and venule hemodynamics are displayed in Figure 1. The arteriole results showed an interesting contrast between effects at 1 hr and 24 hrs post‐ECC. At 1 hr post‐ECC, the DRP group displayed a statistically lower arteriole diameter compared to the LR group, but no statistical difference in blood flow between the two groups. At 24 hrs post‐ECC, no difference in arteriole diameter was observed between groups, while arteriole blood flow was statistically higher in the DRP group compared to the LR group. In venules, no changes were observed between groups at 1 hr post‐ECC. However, at 2 and 24 hrs post‐ECC, the DRP group had a statistically significant higher diameter compared to the LR group. Venular blood flow was statistically elevated in the DRP group at 24 hrs post‐ECC compared to the LR group. Figure 2 shows the changes in FCD. FCD was lower for both DRP and LR groups at 1 and 2 hrs post‐ECC when compared to BL levels. The DRP group displayed a higher FCD at 2 hrs post‐ECC compared to the LR group. At 24 hrs however, while the DRP group was able to recover back to BL levels, the LR group was statistically lower than BL.From these results we conclude that the addition of DRPs to priming fluids for ECC procedures may be beneficial in preserving microvascular perfusion 24 hrs post‐ECC. This may help reduce the risk of ischemic injury, production of pro‐inflammatory markers, and development of multiorgan dysfunction. Further research is warranted to optimize the DRPs parameters, such as concentration and molecular weight.

Longitudinal assessment of spiral artery and intravillous arteriole blood flow and adverse pregnancy outcome.

Superb microvascular imaging (SMI) has been shown to improve visualization of small vessels by suppressing global motions while preserving low-flow components, such as the microvessels in the placenta. We sought to determine if SMI-aided visualization of flow velocity waveforms in the spiral arteries (SA) and intravillous fetal arterioles (IVA) could predict fetal growth restriction (FGR), gestational hypertension (GH) and/or pre-eclampsia (PE). This was a prospective longitudinal study of singleton pregnancies without fetal anomaly, receiving prenatal care in one of two medical centers over a 5-year period. Using SMI-aided color Doppler, SA and IVA flow velocity was measured at three timepoints: 11 + 0 to 14 + 0, 18 + 0 to 22 + 6 and 28 + 0 to 34 + 6 weeks of gestation. SA and IVA flow velocity waveforms were reported as resistance indices (RI). RI values were analyzed using multilevel modeling; individual regression curves were estimated and combined to obtain the reference intervals for SA-RI and IVA-RI in uncomplicated pregnancies. The primary clinical outcome was FGR and secondary outcomes were PE and GH. FGR was defined as estimated fetal weight < 10th percentile. Student's t-test was used to compare deviation from expected RI between normal and complicated pregnancies. Among 540 pregnancies included in the analysis, 18 (3.3%) had FGR, 31 (5.7%) PE and 61 (11.3%) GH. In uncomplicated pregnancies, the SA-RI decreased progressively with advancing gestation, whereas the IVA-RI increased with gestational age. In the third trimester, the mean SA-RI and IVA-RI values were significantly higher in the FGR group compared with pregnancies that did not develop FGR, while the mean SA-RI was significantly higher in PE compared with non-PE pregnancies. There was no significant difference in mean SA-RI or IVA-RI between pregnancies with vs those without GH at any gestational age. When all three adverse outcomes were combined, SA-RI was significantly higher in pregnancies with these outcomes when compared to uncomplicated pregnancies in the third trimester (mean ± SD, 0.29 ± 0.12 vs 0.26 ± 0.12; P = 0.02). In screening for FGR using SA-RI, the areas under the receiver-operating-characteristics curves (AUC) were 0.68, 0.73 and 0.73 in the first, second and third trimesters, respectively. The respective AUCs for IVA-RI were 0.72, 0.72 and 0.73 for each trimester. SA-RI and IVA-RI, measured using SMI technology, were significantly higher in pregnancies at risk for FGR in late gestation. Larger studies are needed to determine if SA and IVA flow are reliable predictors of adverse pregnancy outcome. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Влияние высокопористого керамического материала-имплантата на основе системы ZrO2 – Y2O3 – Al2O3 на жизненные показатели экспериментальных животных

Nanodispersed xerogels and powders (average size 9 nm) were obtained by co-precipitation of hydroxides in the ZrO2–Y2O3–Al2O3. Solid-state sintering of samples from the initial [(ZrO2)0,97(Y2O3)0,03]0,8(Al2O3)0,2 powder with pore-forming additives using a patented technology strong highly porous ceramics was produced. Dopplerography was used to assess the volume of blood flow in arterioles and capillaries on 150 and 250 days after implantation of the plates. Thus, microcirculatory Doppler sonography seems to be a promising intravital method for assessing blood flow in the plate location area and, possibly, inside the plate. It was found that ceramic plates based on zirconium dioxide, placed in the body of experimental animals, do not cause a negative reaction of the animal’s body. The results of studies under in vivo conditions suggest that the obtained bioceramic based on zirconium dioxide is promising for use as a material for endo-prosthetics.

Abstract 10367: An Unusual Vasodilator Response: Recognizing a Rare Subtype of Pulmonary Arterial Hypertension

Introduction: Pulmonary veno-occlusive disease (PVOD) is a rare subtype of pulmonary arterial hypertension (PAH) caused by intimal fibrosis of the pulmonary venules and septal veins. While the hemodynamic profile is suggestive of pre-capillary pulmonary hypertension, vascular obstruction distal to the pulmonary capillary beds distinguishes PVOD from other forms of PAH. Case: A 29-year-old woman presented with progressive dyspnea and fatigue. She was tachycardic, hypotensive, and volume overloaded on exam. ECG was notable for right-axis deviation. TTE showed a dilated, hypokinetic RV and small LV with mild global hypokinesis and septal flattening throughout the cardiac cycle. A CTA chest excluded pulmonary embolism but showed diffuse centrilobular ground-glass opacities and lymphadenopathy which raised suspicion for PVOD. She underwent right heart catheterization with the following measurements (mmHg): RA 14, PA 99/56 (mean 71), PCWP 12, and CI 1.1 L/min/m 2 with PVR 28.1 WU. Following initiation of an epoprostenol infusion, she became increasingly hypoxemic with repeat CT chest demonstrating dramatic worsening of ground-glass opacities and vascular congestion. This response to a vasodilator challenge led to a clinical diagnosis of PVOD. She was urgently listed for and underwent bilateral lung transplantation. Explanted lung tissue subsequently confirmed the diagnosis. Conclusion: In most forms of PAH, vasodilators mitigate arteriolar narrowing and improve pulmonary blood flow, while in PVOD they exacerbate pulmonary capillary congestion due to increased arteriolar blood flow relative to the venous outflow due to fixed narrowing of the pulmonary venule network. Because lung biopsy is contraindicated in severe pulmonary hypertension, the clinician must recognize that worsening pulmonary edema in response to vasodilator challenge with normal PCWP is a critical clue pointing towards PVOD. Timely diagnosis is essential given the poor prognosis for this condition for which lung transplantation is the definitive treatment.

BIOMICROSCOPY OF THE CAPILLARY FLOW - INTERDISCIPLINARY APPROACH AND EFFECTIVENESS OF PATHOLOGICAL CONDITIONS DIAGNOSTICS

The goal – to evaluate the features and diagnostic value of the capillary bedbiomicroscopy results in various pathological conditions.Material and methods. The paper presents data on microcirculation study in patientsof various ages (adults and children) with different somatic pathologies (with diabetesmellitus, arterial hypertension, chronic gastroduodenitis, acute bronchitis) comparedwith healthy persons. The state of microcirculation was recorded using a digital USBmicroscope and evaluated by qualitative and semi quantitative assessment.Results. In patients with diabetes, the most changes in the form of capillariesand venules microaneurism, reduction of the functioning vessels number, slowingblood flow, decrease of arteriolo-venular coefficient were registered. In arterialhypertension, the signs of an increase in peripheral resistance were dominated, andin inflammatory diseases of the gastroduodenal zone and during bronchitis there wasa slowing of blood flow in arterioles and capillaries, an increase in the vascularity ofarterioles and the erythrocytes adhesion inside vessels.Conclusions. Biomicroscopy is simple and informative method for studyingmicrocirculation both chronic and acute diseases, the volume and nature of violationspredominantly depends on the type of pathology, its severity and duration.

The Role of Endothelial Glycocalyx In the Regulation of Retinal Perfusion

Introduction The endothelial glycocalyx is a mesh-like network of proteoglycans and glycoproteins present luminally on the endothelium. Both computational and experimental studies suggest that the presence of the glycocalyx regulates microvascular perfusion and promotes homogeneous blood flow. This function of the glycocalyx in the retina has yet to be investigated; therefore, in this study we try to characterize the role of the retinal glycocalyx in the regulation of retinal hemodynamics and perfusion. Methods Hyaluronidase (25 mg/kg body weight) and heparinase I/III (1 U/mouse) were injected i.v. for 30 minutes via femoral vein cannulation to degrade the glycocalyx. Fluorescently labelled red blood cells were used to measure retinal vascular velocity, and fluorescent dextran (MW = 2000 kD) was used to measure diameters and mean circulation times. Blood flow was calculated as velocity ´ p ´ diameter2/4, and arteriolar and venular shear rates were calculated as 8 ´ velocity/diameter. Results In the retina, glycocalyx degradation led to significant increases in both arteriolar (7%, p=0.018) and venular (16%, p=0.003) lumen diameters filled with high molecular weight dextran, with a more prominent effect on venular diameter. Following the loss of glycocalyx, we observed a tendency (not significant) of an increase in arteriolar velocity, however, no effect was observed on venular velocities. The removal of heparan sulfate and hyaluronic acid led to a substantial increase in arteriolar (24%, p=0.02), venular (28%, p=0.0502), and total blood flow (26%, p=0.029). However, no changes were observed in mean circulation time through the retina. Further, the enzymatic treatment led to a significant decrease in venular (14%, p=0.03), but not arteriolar, shear rates. Conclusions Our study suggests that degradation of the glycocalyx can cause changes in retinal perfusion.

Calciphylaxis in Patients with Chronic Kidney Disease Case Presentation and Review

Calciphylaxis is a serious disorder that presents itself as ischemia and ne-crosis of the skin which occurs more frequently in patients with an end-stage chronic kidney disease, but not exclusively. The pathogenesis is a result of the reduction of arteriolar blood flow, caused by calcification, fibrosis, and thrombus formation that primarily involve the arterioles of the dermis and hypodermis, with a poor prognosis. Case presentation: A 44-year-old patient with a previous diagnosis of chronic kidney disease receiving hemodialysis secondary to polycystic kidney disease, with a history of parathyroidectomy due to primary hyperparathyroidism in 2011. In 2014 the patient presented skin lesions, for which a diagnostic biopsy of calciphylaxis was performed and began treatment with sodium thiosulfate with a poor progression and evolution. New histology compatible with the diagnosis of pyoderma gangrenosum and findings of calciphylaxis were performed. The patient begins treatment with corticosteroids and cyclosporine, with poor clinical evolution and the patient eventually passes away. The objective of this manuscript is to understand this pathology better, which is infrequent but with a high rate of morbidity and mortality.