Microsphere Technique Research Articles

Evaluate the Low-volume resuscitation based on cell impermeant in hemorrhagic shock

To see what function cell swelling played in severe hemorrhagic shock and resuscitation injury. This study was done in the department of General surgery after ethical permission from December 2019 to September 2021. Adult rats were administered a low volume resuscitation (LVR) (10–20 percent blood volume) with saline or several cell impermeants (sorbitol, raffinose, trehalose, gluconate, and Polyethylene glycol-20k) after being haemorrhaged to a pressure of 30–35 mm Hg and kept there until plasma lactate reached 10 mM. (PEG-20k). When lactate returned to 10 mM after LVR, complete resuscitation using crystalloid and red cells was initiated. The rats were euthanized one hour after complete resuscitation. The colourful microsphere technique was used to measure capillary blood flow. Impermeants significantly enhanced LVR outcomes in shocked rats by preventing ischemia-induced cell swelling in liver tissue. In comparison to saline, small cell impermeants and PEG-20k in LVR solutions increased tolerance to the low flow condition by 2 and 5 fold, normalised arterial pressure during LVR, and reduced plasma lactate after full resuscitation.

Postdecompressive spinal cord blood flow increments in a cervical chronic myelopathy model in rats.

In cervical spondylotic myelopathy (CSM), compromise of blood flow to the compressed spinal cord has been postulated to contribute to the development of myelopathy. Although decompressive surgery has been considered to improve spinal cord blood flow, evidence to support this notion is scarce. To determine whether blood flow improves after decompressive surgery for CSM, regional blood flow was measured in a model of chronic cervical compression in rats by using a fluorescent microsphere technique. Thin polyurethane sheets, measuring precisely 3 × 5 × 0.7 mm, were implanted under the C5-6 laminae in 24 rats to induce continuous compression on the cervical spinal cord. These sheets expand gradually by absorbing tissue fluid. This animal model has been demonstrated to reproduce the clinical features and histological changes of CSM, including progressive motor weakness with delayed onset and insidious tissue damage prior to symptom onset. Twenty-four rats that underwent sham operation were allocated to a control group. To confirm the development of cervical myelopathy, motor functions were measured weekly over the study period. Nine weeks after implantation of the sublaminar expanding sheets, histological studies and C5-6 decompressive surgery were conducted. Regional blood flow in the brainstem and cervical spinal cord was measured sequentially until 120 minutes after decompression. In the CSM group, bilateral forepaw grip strength deteriorated progressively from 5 weeks after implantation. In the compressed C5-6 segment of the spinal cord, significant flattening of the cord, a decreased number of motor neurons, and vacuolations of gray matter were demonstrated. In the control group, blood flow in the brainstem and cervical spinal cord was unchanged by the decompressive surgery. In the CSM group, however, diminished blood flow and continuous blood flow increments for 120 minutes after decompression were demonstrated in the compressed C5-6 spinal cord segment. Chronic mechanical compression induced regional spinal cord blood flow insufficiency concomitant with progressive neuronal loss and motor dysfunction in a chronic compression model in rats. Decompressive surgery increased spinal cord blood flow. These findings suggest that blood flow recovery may contribute to postoperative neurological improvement.

Comparison Between Two Pharmacologic Strategies to Alleviate Rewarming Shock: Vasodilation vs. Inodilation.

Rewarming from hypothermia is often challenged by coexisting cardiac dysfunction, depressed organ blood flow (OBF), and increased systemic vascular resistance. Previous research shows cardiovascular inotropic support and vasodilation during rewarming to elevate cardiac output (CO). The present study aims to compare the effects of inodilatation by levosimendan (LS) and vasodilation by nitroprusside (SNP) on OBF and global oxygen transport during rewarming from hypothermia. We used an in vivo experimental rat model of 4 h 15°C hypothermia and rewarming. A stable isotope-labeled microsphere technique was used to determine OBF. Cardiac and arterial pressures were monitored with fluid-filled pressure catheters, and CO was measured by thermodilution. Two groups were treated with either LS (n = 7) or SNP (n = 7) during the last hour of hypothermia and throughout rewarming. Two groups served as hypothermic (n = 7) and normothermic (n = 6) controls. All hypothermia groups had significantly reduced CO, oxygen delivery, and OBF after rewarming compared to their baseline values. After rewarming, LS had elevated CO significantly more than SNP (66.57 ± 5.6/+30% vs. 54.48 ± 5.2/+14%) compared to the control group (47.22 ± 3.9), but their ability to cause elevation of brain blood flow (BBF) was the same (0.554 ± 0.180/+81 vs. 0.535 ± 0.208/+75%) compared to the control group (0.305 ± 0.101). We interpret the vasodilator properties of LS and SNP to be the primary source to increase organ blood flow, superior to the increase in CO.

CART decreases islet blood flow, but has no effect on total pancreatic blood flow and glucose tolerance in anesthetized rats

Cocaine- and amphetamine-regulated transcript (CART) is a neurotransmitter and hormone, involved in the regulation of e.g. food intake, body weight, reward and addiction, and stress response. CART has also been found to affect insulin secretion and beta cell morphology, both in vivo and in vitro. Furthermore, CART affects regulation of the cardiovascular system and helps to modulate vascular tone. The present study evaluated the local effect of CART on the pancreatic and islet circulation and function. CART (25 μg/h) or saline, combinations of CART and endothelin-A receptor antagonist (BQ123; 100 μg/kg), and glucose (2 g/kg) were intravenously infused in Sprague Dawley rats followed by blood flow measurements using a microsphere technique. Separately, CART-infused animals underwent an intravenous glucose tolerance test (ivGTT). The direct effect of CART on insulin release was investigated using isolated islets from Sprague Dawley rats. CART reduced islet blood flow, without reduction in total pancreatic blood flow. The normal glucose-induced islet blood flow increase was diminished by CART, albeit still present. Simultaneously, CART had no effect on systemic-, intestinal- or renal blood flow. The endothelin-A receptor antagonist BQ123 together with CART had no pancreatic vascular effects. We found that CART has pronounced vascular constrictive actions restricted to the pancreatic islet circulation but had no effect on insulin release neither in vivo nor in vitro. The mechanisms behind the vascular effects are still unknown, but may reflect a direct action on pancreatic blood vessels.

Noninvasive estimation of quantitative myocardial blood flow with Tc-99m MIBI by a compartment model analysis in rat

BackgroundWe aimed to investigate the use of dynamic cardiac planar images to estimate myocardial blood flow (MBF) by a compartment model analysis using time-to-peak (TP) map and compared it by the microsphere technique in rat. Positron emission tomography is considered the gold standard method, but is not available everywhere. By contrast, although myocardial perfusion imaging (MPI) with single-photon tracers is more widely available, it may be difficult to obtain adequate region of interest (ROI) settings. We proposed using the TP map to set the ROI, and hypothesized that this method could facilitate the measurement of absolute MBF by MPI in rat. MethodsTwenty-one normal rats were studied. Dynamic planar images with Tc-99m MIBI were obtained, and input function and cardiac ROIs were set using the obtained TP map. MBF was estimated by a one-compartment model analysis with the Renkin-Crone model and by the microsphere technique. ResultsThe MBFs from these two methods were significantly correlated. A negative proportional bias was observed, but no significant difference was observed between the mean MBFs calculated with each method. ConclusionsMBF estimation by a compartment model analysis using TP map could facilitate absolute MBF measurement in rats.

Relationship between hemodynamic parameters and cerebral blood flow during cardiopulmonary resuscitation

IntroductionCerebral blood flow during cardiopulmonary resuscitation (CPR) is a major neuroprognostic factor although not clinically feasible for routine assessment and monitoring. In this context, a surrogate marker for cerebral perfusion during CPR is highly desirable. Yet, cerebral blood flow hemodynamic determinants remain poorly understood and their significance might be altered by changes in head positioning such as flat, head up, and head down during CPR. HypothesisWe hypothesized that routinely measured hemodynamic parameters would correlate with cerebral brain flow during CPR, independently of the head position. MethodsAssociations between cerebral blood flow, measured using microsphere techniques, and hemodynamic parameters were studied from two prior publications. Eight pigs receiving CPR with an automated device and an impedance threshold device in the flat or supine, whole body head down and whole body head up tilt positions were analysed for the derivation sample. Relevant associations were examined for consistency in an external validation sample consisting of 18 pigs randomized to supine position versus head and torso elevation. ResultsAfter adjusting for position, arterial blood pressure and cerebral perfusion pressure during decompression were significantly associated with cerebral blood flow, in the derivation and the external validation samples. No significant associations were found between cerebral blood flow during CPR and right atrial pressure, intracranial pressure, end tidal CO2, carotid blood flow, and coronary perfusion pressure in the derivation sample. ConclusionDecompression arterial blood pressure and cerebral perfusion pressure are relevant candidate surrogate markers for cerebral blood flow during CPR, independently of head position.

Organ blood flow in response to infusion of arginine vasopressin in premature fetal sheep.

Arginine vasopressin (AVP) infusion has been shown to be a useful strategy for the management of systemic perfusion failure in premature infants. Our objective was to determine the characteristics of the blood flow redistribution induced by AVP infusion in premature fetal sheep. Nine sheep fetuses at 99 to 113days of gestation were continuously infused with AVP. Measurement of blood flow to individual fetal organs was performed using a colored microsphere technique, with measurements performed at 30min before and 90min after the initiation of AVP infusions. The AVP infusion significantly increased blood flow to the medulla oblongata (P < 0.05), and significantly decreased flow to the adrenal glands (from 492.0 ± 239.6 to 364.9 ± 143.3mL/min/100g, P < 0.05) and heart (from 592.6 ± 184.5 to 435.6 ± 137.4mL/min/100g, P < 0.05). The infusion significantly increased the vascular resistance in adrenal glands, kidneys, ileum, colon, heart, and cerebellum. In the brain, except for the cerebellum, no significant increase in resistance was identified. There was no significant response to AVP infusion in cerebral blood flow in mid-gestation fetal sheep. Our observations suggest that, under AVP stimulation, the blood flow to the adrenal glands and myocardium might be decreased due to an increase in vascular resistance.

Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 Rats.

Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially, the development of fibrosis and portal hypertension in NAFLD patients requires treatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertension but without obesity. This study investigated the additional role of obesity in this model on the development of portal hypertension and fibrosis. Obesity was induced in twelve-week old TGR(mREN2)27 rats after receiving Western diet (WD) for two or four weeks. Liver fibrosis was assessed using standard techniques. Hepatic expression of transforming growth factor-β1 (TGF-β1), collagen type Iα1, α-smooth muscle actin, and the macrophage markers Emr1, as well as the chemoattractant Ccl2, interleukin-1β (IL1β) and tumor necrosis factor-α (TNFα) were analyzed. Assessment of portal and systemic hemodynamics was performed using the colored microsphere technique. As expected, WD induced obesity and liver fibrosis as confirmed by Sirius Red and Oil Red O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increased during feeding of WD, indicating infiltration of macrophages into the liver, even though this increase was statistically not significant for the EGF module-containing mucin-like receptor (Emr1) mRNA expression levels. Of note, portal pressure increased with the duration of WD compared to animals that received a normal chow. Besides obesity, WD feeding increased systemic vascular resistance reflecting systemic endothelial and splanchnic vascular dysfunction. We conclude that transgenic TGR(mREN2)27 rats are a suitable model to investigate NAFLD development with liver fibrosis and portal hypertension. Tendency towards elevated expression of Emr1 is associated with macrophage activity point to a significant role of macrophages in NAFLD pathogenesis, probably due to a shift of the renin–angiotensin system towards a higher activation of the classical pathway. The hepatic injury induced by WD in TGR(mREN2)27 rats is suitable to evaluate different stages of fibrosis and portal hypertension in NAFLD with obesity.

Effects of Intrathoracic Pressure changes on Diaphragmatic Blood Flow during Mechanical Ventilation

IntroductionAlthough mechanical ventilation (MV) is a life‐saving intervention, prolonged MV can lead to deleterious effects on diaphragm function, such as ventilator‐induced diaphragmatic dysfunction (VIDD) and vascular incompetence. Specifically, prolonged MV elicits time‐dependent reductions in diaphragm blood flow, induces vascular dysfunction, and limits the hyperemic response to contractions associated with weaning. During MV, positive‐end expiratory pressure (PEEP) is used to maintain small airway patency and mitigate alveolar damage; yet increased intrathoracic pressure with high levels of PEEP may impair diaphragm perfusion.PurposeTo test the following hypotheses: 1) Diaphragm blood flow during MV will be less with high vs. low‐peep, and 2) ablation of intrathoracic pressures (via pneumothorax (PTX)) will not alter diaphragm blood flow during MV vs. the low‐peep condition.MethodsFemale Sprague‐Dawley rats (~5 mo) were randomly divided into low PEEP (LP; 1cmH2O, n=7) or high PEEP (HP; 9 cmH2O, n=6) groups during mechanical ventilation. Blood flow, via the fluorescent microsphere technique, was determined during spontaneous breathing (SB) and 10 minutes after intubation and the onset of MV with LP or HP. Thereafter, for a third determination of diaphragm blood flow, the LP group underwent a surgical laparotomy (LAP; to determine effects of intrabdominal pressure on perfusion) and the HP group was subjected to a pneumothorax (PTX), with microsphere infusions occurring 10 minutes after the completion of surgery. Following the final fluorescent microsphere infusion, tissues were harvested for blood flow analysis. The diaphragm was sectioned into costal (ventral, medial, and dorsal) and crural portions to determine diaphragmatic blood flow distribution.ResultsCompared to SB, both LP and HP MV significantly reduced diaphragm medial costal blood flow (LP, 61.9 ± 7.5 vs 43.8 ± 4.9; HP, 46.2 ± 7.7 vs 21.8 ± 3.7 mL/100g/min; P≤0.05). HP MV significantly reduced blood flow to the ventral and medial costal diaphragm compared to LP MV (P≤0.05). In the HP MV+PTX condition, medial and dorsal costal blood flow was significantly increased versus HP MV (P≤0.05). LP MV + LAP did not significantly increase diaphragm blood flow compared to LP MV. Diaphragm perfusion during HP MV+PTX and LP MV were not different (P&gt;0.05).ConclusionThis study demonstrates that HP MV reduces diaphragmatic blood flow to a greater extent than LP MV. Following a PTX in the HP MV condition, diaphragmatic blood flow is not different compared to the LP MV condition, suggesting that the reductions in diaphragmatic blood flow with LP MV are independent of intrathoracic pressure changes, and due likely to diaphragm quiescence.Support or Funding InformationSupported by: NIH HL137156‐01A1

Analysis of spinal cord blood supply combining vascular corrosion casting and fluorescence microsphere technique: A feasibility study in an aortic surgical large animal model.

Spinal cord ischemia after cardiovascular interventions continues to be a devastating problem in modern surgery. The role of intraspinal vascular networks and anterior radiculomedullary arteries (ARMA) in preventing spinal cord ischemia is poorly understood. Landrace pigs (n = 30, 35.1 ± 3.9 kg) underwent a lateral thoracotomy. Fluorescent microspheres were injected into the left atrium and a reference sample was aspirated from the descending aorta. Repeated measurements of spinal cord and renal cortical blood flow from the left and right kidneys with three different microsphere colors in five pigs were taken to validate reproducibility. Spinal cord blood flow to the upper thoracic (T1-T4), mid-thoracic (T5-T8), lower thoracic (T9-T13), and lumbar (L1-L3) levels were determined. After euthanasia, we carried out selective vascular corrosion cast and counted the left and right ARMAs from levels T1-T13. Blood flow analysis of the left and right kidneys revealed a strong correlation (r = .94, p < .001). We detected more left than right ARMAs, with the highest prevalence at T4 (p < .05). The mean number of ARMAs was 8 ± 2. Their number in the upper thoracic region ranged from 2 to 7 (mean of 5 ± 1), while in the lower thoracic region they ranged from 0 to 5 (mean of 3 ± 1 [p < .001]). This study shows that combining fluorescence microsphere technique and vascular corrosion cast is well suited for assessing the blood flow and visualizing the arteries at the same time.

The Physiology of Oxygen Transport by the Cardiovascular System: Evolution of Knowledge

The heart, vascular system, and red blood cells play fundamental roles in O2 transport. The fascinating research history that led to the current understanding of the physiology of O2 transport began in ancient Egypt in 3000 BC, when it was postulated that the heart was a pump serving a system of distributing vessels. Over 4 millennia elapsed before William Harvey (1578-1657) made the revolutionary discovery of blood circulation, but it was not until the 20th century that a lucid and integrative picture of O2 transport finally emerged. This review describes major research achievements contributing to this evolution of knowledge. These achievements include the discovery of the systemic and pulmonary circulations, hemoglobin within red blood cells and its ability to bind O2, and diffusion of O2 from the capillary as the final step in its delivery to tissue. The authors also describe the classic studies that provided the initial description of the basic regulatory mechanisms governing heart function (Frank-Starling law) and the flow of blood through blood vessels (Poiseuille's law). The importance of technical advances, such as the pulmonary artery catheter, the blood gas analyzer and oximeter, and the radioactive microsphere technique to measure the regional blood flow in facilitating O2 transport-related research, is recognized. The authors describe how religious and cultural constraints, as well as superstition-based medical traditions, at times impeded experimentation and the acquisition of knowledge related to O2 transport.

Study on Sintering Kinetics of (Th x Ce1-x )O2 Ceramic Pellets Prepared via Sol-Gel Method

(ThxCe1-x)O2 microspheres (x = 0.50, 0.75, and 0.95) prepared by sol-gel microsphere technique were compacted to pellets. The sintering kinetics, diffusion mechanism, and activation energy of the (ThxCe1-x)O2 pellets were investigated by dilatometry for 1100°C, 1200°C, and 1300°C. The rate controlling sintering method, one of the most sensitive methods, was chosen to investigate the sintering kinetics. The pellets were heated with a rate of 10°C/min and were held for 10 h at the above mentioned temperatures under isothermal conditions. The activation energies for the (Th0.50Ce0.50)O2, (Th0.75Ce0.25)O2, and (Th0.95Ce0.05)O2 pellets were calculated as 305, 315, and 419 kJ·mol−1, respectively. In the experiments, green densities of the mixed-oxide pellets were determined as 45% to 47% of the theoretical density for all of the studied ratios. Sintering densities reached up to 94% of theoretical density after sintering at 1300°C. Scanning electron microscopy images of the pellets were taken.

Hemodynamic and Metabolic Determinants of End-Organ Perfusion and Microcirculation in an Animal Model of Thoracoabdominal Aortic Repair

Introduction - Open repair of thoracoabdominal aorta (TAA) requires prolonged aortic crossclamping and extracorporeal circulation. Hybrid repair with proximal endovascular graft fixation can reduce ischemic time and eliminate the need for the pump. We measured the effects of hybrid approach on intraoperative and recovery hemodynamics in an experimental pig model. Methods - Four approaches were compared; group 1: open surgical TAA repair, group 2: 1st generation SPIDER graft, group 3: 2nd generation SPIDER with loop graft for implantation of lumbar arteries, and group 4: 3rd generation SPIDER graft with volume-based resuscitation. Hemodynamic variables, tissue perfusion, branch vessel flow, and clinical laboratory values were measured at baseline, at end-operation and at six hours (6H) postoperatively. Organ microperfusion was measured by gold-standard fluorescent microsphere (MS) technique. Data were analyzed by hierarchical linear mixed models to account for multilevel repeated measurements. Results - 27 pigs (75-85 kg) were studied. Total ischemic times were significantly longer for open grafts than SPIDER grafts for all branch vessels (p<0.0001). Branch vessel flows were not present in the OSR group during crossclamping, but recovered at clamp release and 6H postoperatively. Perfusion of the visceral organs measured by fluorescent microsphere varied significantly between baseline, post-implant and 6H postoperatively in all groups (p<0.0001). Between graft types, highly significant time-by-group interactions were observed for liver and bowel (all p<0.015). Hierarchical modeling demonstrated significant multilevel correlational influence of macro-hemodynamic changes (celiac or SMA flow and ischemic time) on microcirculation (end-organ perfusion) of hepatic and mesenteric beds (multilevel R2 0.61). Lactate levels were strongly correlated with bowel but not liver perfusion. Conclusion - Hybrid grafts significantly reduce intraoperative ischemia, end-organ perfusion abnormalities and metabolic derangements during thoracoabdominal aortic repair.

TGR(mREN2)27 rats develop non-alcoholic fatty liver disease-associated portal hypertension responsive to modulations of Janus-kinase 2 and Mas receptor

Prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. Resulting fibrosis and portal hypertension, as a possible secondary event, may necessitate treatment. Overexpression of mouse renin in the transgenic rat model, TGR(mREN2)27, leads to spontaneous development of NAFLD. Therefore, we used TGR(mREN2)27 rats as a model of NAFLD where we hypothesized increased susceptibility and investigated fibrosis and portal hypertension and associated pathways. 12-week old TGR(mREN2)27 rats received either cholestatic (BDL) or toxic injury (CCl4 inhalation). Portal and systemic hemodynamic assessments were performed using microsphere technique with and without injection of the Janus-Kinase 2 (JAK2) inhibitor AG490 or the non-peptidic Ang(1-7) agonist, AVE0991. The extent of liver fibrosis was assessed in TGR(mREN2)27 and wild-type rats using standard techniques. Protein and mRNA levels of profibrotic, renin-angiotensin system components were assessed in liver and primary hepatic stellate cells (HSC) and hepatocytes. TGR(mREN2)27 rats developed spontaneous, but mild fibrosis and portal hypertension due to the activation of the JAK2/Arhgef1/ROCK pathway. AG490 decreased migration of HSC and portal pressure in isolated liver perfusions and in vivo. Fibrosis or portal hypertension after cholestatic (BDL) or toxic injury (CCl4) was not aggravated in TGR(mREN2)27 rats, probably due to decreased mouse renin expression in hepatocytes. Interestingly, portal hypertension was even blunted in TGR(mREN2)27 rats (with or without additional injury) by AVE0991. TGR(mREN2)27 rats are a suitable model of spontaneous liver fibrosis and portal hypertension but not with increased susceptibility to liver damage. After additional injury, the animals can be used to evaluate novel therapeutic strategies targeting Mas.

Ghrelin in rat pancreatic islets decreases islet blood flow.

The peptide ghrelin is mainly produced in some of the epithelial cells in the stomach, but also, during starvation, by the ε-cells in the endocrine pancreas. Ghrelin, as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1α), exerts a variety of metabolic functions including stimulation of appetite and weight gain. Its complete role is not yet fully understood, including whether it has any vascular functions. The present study evaluated if ghrelin affects pancreatic and islet blood flow. Ghrelin and the GHS-R1α receptor antagonist GHRP-6 were injected intravenously in rats followed by blood flow measurements using a microsphere technique. Ghrelin decreased, while GHRP-6 in fasted, but not fed, rats selectively increased islet blood flow fourfold. GHS-R1α was identified not only on glucagon-producing cells but also seemed to be present in the islet arterioles. GHRP-6 in fasted rats, only, also improved the peak insulin response to glucose in vivo, thereby substantially blunting the hyperglycemia. GHRP-6 doubled glucose-stimulated insulin release in vitro of both islets obtained from fed and fasted rats. Our results indicate a novel role for endogenous ghrelin acting directly or indirectly as a local vasoconstrictor in the islets during fasting, thereby restricting the insulin response to hyperglycemia. This is to the best of our knowledge the first report that shows this physiological mechanism to restrict insulin delivery from the islets by acting on the vasculature; a mode of action that can be envisaged to complement the previously well-described mechanisms of ghrelin acting directly on the islet endocrine cells.

Pancreatic perfusion and its response to glucose as measured by simultaneous PET/MRI

AimsPerfusion of the pancreas and the islets of Langerhans is sensitive to physiological stimuli and is dysregulated in metabolic disease. Pancreatic perfusion can be assessed by both positron emission tomography (PET) and magnetic resonance imaging (MRI), but the methods have not been directly compared or benchmarked against the gold-standard microsphere technique.MethodsPigs (n = 4) were examined by [15O]H2O PET and intravoxel incoherent motion (IVIM) MRI technique simultaneously using a hybrid PET/MRI scanner. The pancreatic perfusion was measured both at basal conditions and after intravenous (IV) administration of up to 0.5 g/kg glucose.ResultsPancreatic perfusion increased by 35%, 157%, and 29% after IV 0.5 g/kg glucose compared to during basal conditions, as assessed by [15O]H2O PET, IVIM MRI, and microspheres, respectively. There was a correlation between pancreatic perfusion as assessed by [15O]H2O PET and IVIM MRI (r = 0.81, R2 = 0.65, p < 0.01). The absolute quantification of pancreatic perfusion (ml/min/g) by [15O]H2O PET was within a 15% error of margin of the microsphere technique.ConclusionPancreatic perfusion by [15O]H2O PET was in agreement with the microsphere technique assessment. The IVIM MRI method has the potential to replace [15O]H2O PET if the pancreatic perfusion is sufficiently large, but not when absolute quantitation is required.

Differential impact of severe familial hypercholesterolemia on regional skeletal muscle and organ blood flows during exercise: effects of PDE5 inhibition

Swine with familial hypercholesterolemia (FH) exhibit attenuated exercise‐induced systemic vasodilation that is restored by phosphodiesterase 5 (PDE5) inhibition. Whether the impacts of FH and PDE5 inhibition to impair and restore, respectively, exercise‐induced vasodilation results from tissue‐specific or generalized effects remains unclear. Thus, we hypothesized that FH induces generalized impairment of skeletal muscle vasodilation that would be alleviated by PDE5 inhibition. Systemic vascular responses to exercise were assessed in chronically instrumented normal and FH swine before and after PDE5 inhibition with EMD360527. Skeletal muscle and organ blood flows and conductances were determined via the microsphere technique. As previously reported, versus normal swine, FH swine have pronounced elevation of total cholesterol and impaired exercise‐induced vasodilation that is restored by PDE5 inhibition. Blood flows to several, not all, skeletal muscle vascular beds were severely impaired by FH associated with reduced blood flow to many visceral organs. PDE5 inhibition differentially impacted skeletal muscle and organ blood flows in normal and FH swine. These data indicate that FH induces regional, not generalized, vasomotor dysfunction and that FH and normal swine exhibit unique tissue blood flow responses to PDE5 inhibition thereby adding to accumulating evidence of vascular bed‐specific dysfunction in co‐morbid conditions.Support or Funding InformationSupported by NIH (HL52490 to MHL, HL136386 to SBB), The Netherlands Cardio Vascular Research Initiative, an initiative with support of the Dutch Heart Foundation (CVON2014‐11, RECONNECT to DM and DJD), and the Department of Veterans Affairs BLR&amp;D (CDA‐2 IK2 BX002030 to SBB).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Differential impact of severe familial hypercholesterolemia on regional skeletal muscle and organ blood flows during exercise: Effects of PDE5 inhibition.

Swine with familial hypercholesterolemia (FH) exhibit attenuated exercise-induced systemic vasodilation that is restored by phosphodiesterase 5 (PDE5) inhibition. Whether the impacts of FH and PDE5 inhibition to impair and restore exercise-induced vasodilation, respectively, results from tissue-specific or generalized effects remains unclear. Thus, we hypothesized that FH induces generalized impairment of skeletal muscle vasodilation that would be alleviated by PDE5 inhibition. Systemic vascular responses to exercise were assessed in chronically instrumented normal and FH swine before and after PDE5 inhibition with EMD360527. Skeletal muscle and organ blood flows and conductances were determined via the microsphere technique. As previously reported, vs normal swine, FH swine have pronounced elevation of total cholesterol and impaired exercise-induced vasodilation that is restored by PDE5 inhibition. Blood flows to several, not all, skeletal muscle vascular beds were severely impaired by FH associated with reduced blood flow to many visceral organs. PDE5 inhibition differentially impacted skeletal muscle and organ blood flows in normal and FH swine. These data indicate that FH induces regional, not generalized, vasomotor dysfunction and that FH and normal swine exhibit unique tissue blood flow responses to PDE5 inhibition thereby adding to accumulating evidence of vascular bed-specific dysfunction in co-morbid conditions.

On the swelling induced microstructural evolution of polymer networks in gels

A gel is formed when a polymer network is submerged in a solvent. The solvent molecules penetrate the network and cause the network to swell. In this paper we propose a microscopically-motivated energy-based framework that captures the equilibrium response of gels. The free energy of a gel comprises four contributions - the entropy of a polymer network, the energy of mixing, a total pressure term stemming from the pressure of the liquid molecules and the network in the gel, and the hydrostatic work of the external pressure exerted by the solvent. To compute the entropy of a polymer network, we employ a Langevin-based microscopically motivated model for a polymer chain that captures its finite extensibility. The integration from the chain to the network level is carried out via the numerical micro-sphere technique. The energetic contribution of the mixing process is described by well established models. The proposed framework allows us to study the micro-structural evolution of the polymer chains as the gel swells. To illustrate the macroscopic response and the evolution of the polymer chains as swelling occurs, we study three cases: (1) swelling under a constant force, (2) swelling under displacement boundary conditions, and (3) swelling of a polymeric tube with a fixed inner radius. In the first two examples, swelling leads to a homogeneous deformation and a non-uniform extension of the chains in the network. In the third case, the deformation and the extension of the chains are heterogeneous. We illustrate the spatial chain-distribution. Interestingly, we find that a fixed internal radius leads to a boundary effect that spatially fades. This work provides a better understanding of the microscopic mechanisms that govern the swelling process and suggests that the response can be controlled by micro-structural design.

In situ printing of liquid superlenses for subdiffraction-limited color imaging of nanobiostructures in nature

The nanostructures and patterns that exist in nature have inspired researchers to develop revolutionary components for use in modern technologies and our daily lives. The nanoscale imaging of biological samples with sophisticated analytical tools, such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM), has afforded a precise understanding of structures and has helped reveal the mechanisms contributing to the behaviors of the samples but has done so with the loss of photonic properties. Here, we present a new method for printing biocompatible “superlenses” directly on biological objects to observe subdiffraction-limited features under an optical microscope in color. We demonstrate the nanoscale imaging of butterfly wing scales with a super-resolution and larger field-of-view (FOV) than those of previous dielectric microsphere techniques. Our approach creates a fast and flexible path for the direct color observation of nanoscale biological features in the visible range and enables potential optical measurements at the subdiffraction-limited scale.