Local Hemodynamic Changes Research Articles

The Role of Biodegradable Poly-(L-lactide)-Based Polymers in Blood Cell Activation and Platelet-Monocyte Interaction.

The main purpose of new stent technologies is to overcome unfavorable material-related incompatibilities by producing bio- and hemo-compatible polymers with anti-inflammatory and anti-thrombogenic properties. In this context, wettability is an important surface property, which has a major impact on the biological response of blood cells. However, the influence of local hemodynamic changes also influences blood cell activation. Therefore, we investigated biodegradable polymers with different wettability to identify possible aspects for a better prediction of blood compatibility. We applied shear rates of 100 s−1 and 1500 s−1 and assessed platelet and monocyte activation as well as the formation of CD62P+ monocyte-bound platelets via flow cytometry. Aggregation of circulating platelets induced by collagen was assessed by light transmission aggregometry. Via live cell imaging, leukocytes were tracked on biomaterial surfaces to assess their average velocity. Monocyte adhesion on biomaterials was determined by fluorescence microscopy. In response to low shear rates of 100 s−1, activation of circulating platelets and monocytes as well as the formation of CD62P+ monocyte-bound platelets corresponded to the wettability of the underlying material with the most favorable conditions on more hydrophilic surfaces. Under high shear rates, however, blood compatibility cannot only be predicted by the concept of wettability. We assume that the mechanisms of blood cell-polymer interactions do not allow for a rule-of-thumb prediction of the blood compatibility of a material, which makes extensive in vitro testing mandatory.

183-OR: Pyruvate Kinase M2 (PKM2) Enzymatic Activity Is Necessary to Improve Podocyte Mitochondrial Function and Glomerular Fuel Metabolism and Diabetic Nephropathy

Diabetic nephropathy (DN) is the result of abnormal systemic and local changes in metabolism and hemodynamics. We have reported that many glycolytic enzymes, such as pyruvate kinase M2 (PKM2), were elevated in the renal glomeruli of type 1 and type 2 diabetic patients who were protected from DN. TEPP46, a small-molecule which activates PKM2 by inducing oligomerization, reversed glomerular pathology in diabetic mice. After 7 months of STZ induced diabetes, mice with PKM2 specific overexpression in podocytes (PPKM2Tg) with podocin promoter, exhibited lower albumin-creatinine ratio (ACR), kidney-body weight ratio, mesangial expansion, basement membrane thickness and podocyte foot process effacement vs. WT diabetic littermates. PPKM2Tg mice exhibited lower expression of fibrotic (FN, TGFβ1 and Col4a) and oxidative stress (p47phox, NOX2 and NOX4) genes and improvement in endothelial function with increased eNOS and VEGF expressions in the glomeruli, compared to diabetic WT mice. Glycolytic and mitochondrial metabolisms as measured by oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using Seahorse showed striking improvement of impaired mitochondrial maximal respiration capacity and glycolytic rate in isolated glomeruli of diabetic PPKM2Tg mice, in concordance with elevated expressions of mitochondrial related-genes, such as PGC1α. Knocking-down PKM by shRNA in podocyte cell line (pPKMKD) replicated metabolic findings induced by diabetes with dramatic decline of both OCR and glycolytic rate. Re-expressing human PKM1 or PKM2 in pPKMKD cell line reversed impaired mitochondrial function and glycolysis, which were not improved in pPKMKD cells re-expressing with enzymatically inactive human PKM2 gene. These results indicate that PKM2 and its enzymatical function are both necessary in podocytes to improve glomerular mitochondrial abnormalities and delay the progression of DN. Disclosure J. Fu: None. G. L. King: Consultant; Self; Agios, Inc., Medtronic, Other Relationship; Self; Janssen Pharmaceuticals, Inc. T. Shinjo: None. Q. Li: None. R. St-louis: None. K. Park: None. H. Yokomizo: None. M. Yu: None. H. Shah: None. I. Wu: None. Funding Iacocca Family Foundation

Intraoperative Early Venous Filling Phenomenon as an Intrinsic Sign of the Local Hemodynamic Change after Revascularization Surgery in a Patient with Adult Moyamoya Disease: Implications of a Potential Arteriovenous Shunt

After revascularization surgery for patients with moyamoya disease (MMD), local and global hemodynamic changes occur intraoperatively and in the early postoperative period. Local cerebral hyperperfusion and watershed shift ischemia are well-known perioperative pathologies after revascularization for MMD, but early venous filling phenomenon is markedly rare. We report the case of a 19-year-old woman with hemorrhagic-onset MMD who presented with grand mal seizure and subarachnoid hemorrhage. She underwent superficial temporal artery (STA)–middle cerebral artery (MCA) anastomosis combined with indirect pial synangiosis on the affected hemisphere. Intraoperatively, notable early arterial blood filling in the fine cortical vein was observed around the site of anastomosis right after the STA–MCA anastomosis under the surgical microscope and fluorescence indocyanine green video angiography. Recovery of consciousness after general anesthesia was normal, although she exhibited a focal seizure 1 hour later. Postoperative magnetic resonance imaging was not remarkable, and cerebral hemodynamics significantly improved in the acute stage after surgical revascularization. Considering the intrinsic vulnerability of the microvascular anatomy of MMD, the present case is notable because early venous filling was observed intraoperatively. This phenomenon suggests the existence of a potential arteriovenous shunt as an underlying pathology of MMD, but its implications in the early postoperative course should be further verified in a larger number of MMD patients undergoing surgical revascularization.

Ischemic complications following surgical treatment of moyamoya disease: risk factors and prevention

One of the most difficult problems in surgical treatment of moyamoya disease is prevention of ischemic perioperative complications. The risk of these events is significantly higher compared to other cerebrovascular diseases (up to 30%). To identify unfavorable prognostic factors of perioperative cerebral ischemic complications, to determine the group of high-risk patients and to develop the guidelines for perioperative management of these patients. We analyzed clinical and diagnostic data and postoperative outcomes in 80 patients with various forms of moyamoya disease. These patients underwent 134 different interventions. Staged revascularization of both hemispheres was performed in 40 patients (80 surgeries). Most patients (n = 55) underwent combined brain revascularization (79 surgeries). Persistent postoperative complications (ischemic stroke) developed in 7 cases (5.3%). Transient neurological impairment was observed in 36 cases (27%). Statistical analysis revealed the following risk factors of perioperative complications: critical stenosis/occlusion of posterior cerebral artery (OR 9.704), severe perfusion deficit (OR 5.393) and previous TIA or ischemic stroke within 3 months prior to surgery (OR 6.433). If at least two of these signs are present, sensitivity of prognosis for postoperative complications is 80.7% and 88.6%, respectively. Patients with moyamoya disease are at high risk of perioperative complications due to complex rearrangement of collateral cerebral circulation and high sensitivity of brain to local and systemic hemodynamic changes. Patients with risk factors require careful perioperative management to exclude pathogenetic factors provoking ischemia. Early surgical treatment is advisable to reduce the risk of ischemic and hemorrhagic lesions following natural course of disease and severe perioperative complications.

Key elements that determine the efficacy of cupping therapy: A bibliometric analysis and review of clinical studies

Abstract Objective The aim of this review was to identify the possible mechanisms behind cupping therapy by employing an evidence-based approach, and to explore its possible regional and systemic effects in the human body. Methods We searched six electronic databases and four online trial registries for articles published up to January 1, 2020. Clinical studies on the mechanisms of retained cupping, flashing cupping, moving cupping, and vacuum cupping were considered for this review. The methodological qualities of controlled studies were assessed using the National Institute for Clinical Excellence methodology checklist, the Newcastle-Ottawa Scale, and the Cochrane risk of bias tool. Characteristic statistical description and qualitative summary of results were used for data analysis. Results Thirty-eight studies (37 full texts and one abstract) were included in this study. Due to the clinical heterogeneity among the studies, we could not conduct a meta-analysis. The results showed that the key factors that contribute to the efficacy of cupping therapy are negative pressure and temperature. Cupping therapy mainly causes local and systemic changes in hemodynamics, immune regulation, metabolism, and pain relief. Conclusion We identified negative pressure as the key element behind cupping therapy. Cupping therapy may cause redistribution of oxygen at the cupping site and in neighboring tissues, thereby inducing a therapeutic effect by increasing regional blood flow. It may also induce metabolic change, immunomodulation, and neuromodulation. However, additional rigorous clinical research needs to be conducted to further clarify the mechanism behind cupping therapy.

Evaluation of Hemodynamic Change by Indocyanine Green-FLOW 800 Videoangiography Mapping: Prediction of Hyperperfusion Syndrome in Patients with Moyamoya Disease.

Objective Hyperperfusion syndrome (HPS) after bypass surgery for moyamoya disease (MMD) mainly results from redistribution of blood flow, which leads to poor outcomes, while effective methods to predict HPS are still lacking. Indocyanine green (ICG) videoangiography can assess regional cerebral blood flow changes semiquantitatively with the application of FLOW 800 software. The purpose of this study was to investigate whether the intraoperative evaluation of local hemodynamic changes around anastomotic sites using FLOW 800 videoangiography mapping can predict the incidence of HPS and clinical outcomes. Methods Of the patients who were diagnosed with MMD in our hospital between August 2018 and December 2019, who underwent superficial temporal artery-middle cerebral artery bypass surgeries, we investigated 65 hemispheres (in 62 patients) in which intraoperative ICG analysis was performed using FLOW 800 (Zeiss Meditec, Oberkochen, Germany) to evaluate the local cerebral hemodynamics before and after anastomosis. Regions of interest were set at more than 2 points on the brain surface according to the location and situation of recipient arteries in the surgical area. Peak cerebral blood volume (CBV), regional cerebral blood flow (CBF), and time to peak (TTP) were calculated from the selected points. As the data were available intraoperatively, anastomoses were performed in a suitable area. According to the occurrence of HPS, patients were divided into the asymptomatic and symptomatic groups, from which hemodynamic parameters were compared. Furthermore, ROC analysis was performed to determine the diagnostic accuracy of change rates in CBV, CBF, and TTP (i.e., ΔCBV, ΔCBF, and ΔTTP) for predicting HPS. Results Data from the 62 patients were analyzed, and all patients were closely assessed during hospitalization after the procedures. The values of ΔCBV and ΔCBF were significantly higher in the symptomatic group (p < 0.01), while ΔTTP is slightly lower in the symptomatic group with no statistical differences (p = 0.72). Hemodynamic parameters including ΔCBV and ΔCBF, calculated by FLOW 800, had high sensitivity and specificity according to the ROC curve (ΔCBV: AUC = 0.743, 95% CI, 0.605–0.881, p = 0.002; ΔCBF: AUC = 0.852, 95% CI, 0.750–0.954, p < 0.01), which could be used as predictors for HPS. Conclusions Intraoperative ICG-FLOW 800 videoangiography mapping is a safe method which can reflect hemodynamic characteristics in the surgical area for MMD, the findings of which correlate with the occurrence of HPS. Parameters including ΔCBV and ΔCBF are proven to be efficient in the prediction of HPS.

The Monitoring and Application of Transcranial Doppler Ultrasound in Patients with Severe Neurovascular Diseases

To investigate the monitoring effect and application of transcranial Doppler ultrasound (TCD) in patients with severe neurovascular cerebrovascular diseases. From December 2016 to October 2018, 96 patients with cerebrovascular disease in Department of Neurology and ICU, West China Hospital, Sichuan University were monitored by bedside TCD, including the detection of bilateral middle cerebral arteries (MCAs) through temporal window, and the detection of the basilar artery (BA) through occipital window, characterized by the peak systolic blood flow velocity, peak diastolic blood flow velocity, average peak blood flow velocity, vascular pulsatility index, vascular pulsatility index, vascular resistance index and blood flow spectrum morphology in local hemodynamic changes. According to the monitoring results, it was divided into vasospasm group, increased blood flow group and insufficient blood supply group. Relevant data of monitoring results were analysed. Bedside TCD monitoring was successfully used to all cerebrovascular diseases patients. Among 96 patients, 37 patients (38.54%) had increased cerebral blood flow, 15 patients (15.62%) had cerebral vasospasm, and 93 patients had insufficient cerebral blood supply (90.62%, including insufficient blood supply to the MCA and BA). Patients mainly with cerebral aneurysm and hypertensive intracerebral hemorrhage types contributed the highest proportion of insufficient blood supply, followed by the increase of blood flow, and the incidence of vasospasm was relatively low. In cerebral aneurysm group and hypertensive intracerebral hemorrhage group, and differences in the incidence of insufficient blood supply, increased blood flow, and vasospasm were statistically significant ( P<0.05). The bedside TCD monitoring can assess the patient's craniocerebral hemodynamic information and provide a clinical guidance.

Regulation of blood flow in small arteries: mechanosensory events underlying myogenic vasoconstriction.

As blood flow is proportional to the fourth power of the vascular radius small changes in the diameter of resistance arteries/arterioles following an increase in intraluminal pressure would be expected to substantially increase blood flow. However, arteriolar myocytes display an intrinsic ability to locally regulate blood flow according to metabolic demands by tuning the diameter of small arteries in response to local changes in he-modynamics. Critical to this, observations were made more than 100 years ago that mechanosensitive small arteries exhibit the “myogenic response” or pressure-induced vasoconstriction or vasodilation in re-sponse to increased or decreased intravascular pressure, respectively. Although cellular mechanisms underlying the myogenic response have now been studied extensively, the precise cellular mechanisms under-lying this intriguing phenomenon still remain uncertain. In particular, the biological machinery that senses changes in intravascular pressure in vascular smooth muscle cells have not been unquestionably identified and remain a significant issue in vascular biology to be fully elucidated. As such, this brief review focuses on putative mechanosensors that have been proposed to contribute to myogenic vasoreactivity. Specific attention is paid to the roles of integrins, G protein-coupled receptors, and cadherins.

307-OR: Activation of Mitochondrial Activities by Pyruvate Kinase M2 (PKM2) in Podocytes Improved Glomerular Metabolism and Diabetic Nephropathy

Diabetic nephropathy (DN) is the result of systemic and local changes in metabolism and hemodynamics. We have found that the elevation of glycolytic enzymes, such as pyruvate kinase M2 (PKM2) in the renal glomeruli is correlated with preservation of renal function in human type 1 and type 2 diabetes. A small-molecule PKM2 activator, TEPP46, prevented or reversed glomerular pathology in diabetic mice of chronic duration. Mice with PKM2 overexpression specifically in podocytes (PPKM2Tg) were generated, which after 7 months of diabetes induced by streptozotocin, exhibited significantly lower albumin-creatinine ratio (ACR), kidney weight-body weight ratio, and glomeruli pathology such as reduced glomeruli size, mesangial expansion, and basement membrane thickness compared to diabetic WT mice. Furthermore, the glomeruli of diabetic PPKM2Tg mice exhibited lower expressions of fibrotic (FN, TGFβ1 and Col4a) and oxidative stress (p47phox, NOX2 and NOX4) genes compared to WT diabetic mice. Interestingly, the decreased expression of endothelial-trophic genes and mitochondrial-related genes were improved in the whole glomeruli of diabetic PPKM2Tg mice. Oxygen consumption rate (OCR) of glomeruli as measured by Seahorse showed significant improvement in diabetic PPKM2Tg mice versus WT mice (p &amp;lt; 0.05). In vitro studies showed that the activation of PKM2 in mouse podocyte cell line by TEPP-46 decreased high glucose-induced ROS production, improved mitochondrial membrane potential (MMP) by increased the level of mitochondrial OCR and enhanced glycolytic rate. Furthermore, PKM-knockdown stable podocyte cell line, mimicking diabetic conditions, showed dramatical decline of OCR and glycolytic rate. These results showed that PKM2 specific overexpression in podocytes can significantly reduce diabetes-induced mitochondrial abnormalities and oxidative stress in the whole glomeruli, and delay the progression of diabetic nephropathy. Disclosure J. Fu: None. T. Shinjo: None. R. St-Louis: None. Q. Li: None. K. Park: None. H. Yokomizo: None. Y. Zaitsu: Employee; Self; Sunstar Group. M. Yu: None. I. Wu: None. H. Shah: None. G.L. King: Research Support; Self; Janssen Pharmaceuticals, Inc.

Short interposition with a small-diameter prosthetic graft for flow reduction of a high-flow arteriovenous fistula

ObjectiveThe objective of this study was to evaluate the outcome of a short interposition using a small-diameter prosthetic graft as a flow-limiting procedure to manage symptomatic high-flow arteriovenous fistula (AVF). MethodsA retrospective review of medical records on a case series was conducted. From June 2004 to April 2017, there were 25 patients with clinical symptoms of high output cardiac failure and progressive dilation of aneurysmal fistula vein due to high-flow AVF (≥1.5 L/min) who underwent short interposition with a 5-mm prosthetic graft at Saitama Medical Center. The primary outcome was the relief of clinical symptoms; other outcome measures included technical success, surgical complications, patency of vascular access, and postoperative changes in local and systemic hemodynamics as assessed by Doppler ultrasound. ResultsTwenty-five patients underwent short interposition for cardiac indications (n = 16) and aneurysmal dilation (n = 9). The technical success rate was 100%. The clinical symptoms were relieved in 24 patients (96.0%). Mean reduction in access blood flow was 52.4%. Cumulative primary unassisted patency rates (± standard error) at 1 year, 2 years, and 3 years were 76.2% ± 9.3%, 70.4% ± 10.3%, and 58.1% ± 11.6%, respectively. Secondary patency rates (± standard error) at 1 year, 2 years, and 3 years were 81.8% ± 8.2%, 71.5% ± 9.9%, and 71.5% ± 9.9%, respectively. Complications included access occlusion due to late thrombosis (n = 5 [21.7%]) and graft infection (n = 1 [4.3%]) in the median follow-up period of 3.9 years. ConclusionsShort interposition with a prosthetic graft is a simple, effective, and durable treatment option for end-stage renal disease patients with cardiac symptoms and progressive dilation of the fistula vein due to high-flow AVF, offering clinical symptom resolution while preserving the autologous behavior of the initial access.

Influence of Artery Straightening on Local Hemodynamics in Left Anterior Descending (LAD) Artery after Stent Implantation.

Objectives The study investigates local hemodynamic environment changes caused by straightening phenomenon and the relationship between straightening phenomenon and in-stent restenosis. Background Intravascular intervention is an effective treatment in restoring the normal flow conditions and vascular lumen. Unfortunately, in-stent restenosis often occurs in a subset of patients after stent implantation and limits the success of stent implantation outcomes. The implanted stent usually causes artery straightening locally, rather than coinciding and adjusting to the physiological curve exactly. Artery straightening would apparently modify the artery geometry and therefore alter the local hemodynamic environment, which may result in intimal hyperplasia and restenosis after stenting implantation. Methods In the current investigation, we verify the hypothesis that the artery straightening influences the local hemodynamic state using the different 3D CT models. Flow analysis for blood in the left anterior descending coronary artery and the straightening model is simulated numerically. Result The current results reveal that the straightening phenomenon alters the distribution of wall shear stress and flow patterns, decreases the wall shear stress (WSS), and increases the oscillatory shear index (OSI) and the relative residence time (RRT), especially at the proximal and distal areas of stenting. Conclusions The local straightened geometry established after stent implantation was likely to generate portions of the stenting area to a high risk of neointimal hyperplasia and subsequent restenosis.

Transcutaneous contrast-enhanced ultrasound imaging of the posttraumatic spinal cord.

Experimental animal study. The current study aims to test whether the blood flow within the contused spinal cord can be assessed in a rodent model via the acoustic window of the laminectomy utilizing transcutaneous ultrasound. Department of Neurological Surgery, University of Washington, Seattle WA. Long-Evans rats (n = 12) were subjected to a traumatic thoracic spinal cord injury (SCI). Three days and 10 weeks after injury, animals underwent imaging of the contused spinal cord using ultrafast contrast-enhanced ultrasound with a Vantage ultrasound research system in combination with a 15 MHz transducer. Lesion size and signal-to-noise ratios were estimated via transcutaneous, subcutaneous, or epidural ultrasound acquisition through the acoustic window created by the original laminectomy. Following laminectomy, transcutaneous and subcutaneous contrast-enhanced ultrasound imaging allowed for assessment of perfusion and vascular flow in the contused rodent spinal cord. An average loss of 7.2 dB from transcutaneous to subcutaneous and the loss of 5.1 dB from subcutaneous to epidural imaging in signal-to-noise ratio (SNR) was observed. The hypoperfused injury center was measured transcutaneously, subcutaneously and epidurally (5.78 ± 0.86, 5.91 ± 0.53, 5.65 ± 1.07 mm2) at 3 days post injury. The same animals were reimaged again at 10 weeks following SCI, and the area of hypoperfusion had decreased significantly compared with the 3-day measurements detected via transcutaneous, subcutaneous, and epidural imaging respectively (0.69 ± 0.05, 1.09 ± 0.11, 0.95 ± 0.11 mm2, p < 0.001). Transcutaneous ultrasound allows for measurements and longitudinal monitoring of local hemodynamic changes in a rodent SCI model.

Contrast-Enhanced Ultrasound for Assessment of Local Hemodynamic Changes Following a Rodent Contusion Spinal Cord Injury.

Severe trauma to the spinal cord leads to a near complete loss of blood flow at the injury site along with significant hypoperfusion of adjacent tissues. Characterization and monitoring of local tissue hypoperfusion is currently not possible in clinical practice because available imaging techniques do not allow for assessment of blood flow with sufficient spatial and temporal resolutions. The objective of the current study was to determine whether ultrafast contrast-enhanced ultrasound (CEUS) imaging could be used to visualize and quantify acute hemodynamic changes in a rat traumatic spinal cord injury (SCI) model. We used novel ultrasound acquisition and processing methods that allowed for measurements of local tissue perfusion as well as for assessment of structural and functional integrity of spinal vasculature. CEUS imaging showed that traumatic SCI results in (1) an area with significant loss of perfusion, which increased during the first hour after injury, (2) structural alterations of the spinal cord vasculature, and (3) significant slowing of arterial blood flow velocities around the injury epicenter. We conclude that CEUS has the spatial and temporal sensitivity and resolution to visualize local tissue perfusion and vessel architecture, which maybe useful clinically to determine injury extent and severity in patients with SCI.

P1823 Feasibility of CCTA in assessment of luminal changes and coronary shear stress evolution after implantation of bioresorbable vascular scaffolds

Abstract Funding Acknowledgements PlaqueImage - financed by the National Authority of Scientific Research and Innovation and the Romanian Ministry of European Funding Background Coronary shear stress (CSS) is a well-established local mechanical factor in atherogenesis, progression and destabilization of atherosclerotic plaques. Analysis of CSS after coronary stent placement is still lacking of large clinical studies. Purpose: The aim of this study was to: (1) test the feasibility of Coronary Computed Tomography Angiography (CCTA) for assessment of local hemodynamic and luminal changes after implantation of bioresorbable vascular scaffolds (BVS), and (2) to investigate CSS modifications after BVS implantation. Methods: We conducted a single center, prospective pilot study on 73 patients with coronary artery disease who underwent elective percutaneous coronary intervention (PCI); group 1 (n = 30) – patients with BVS and group 2 (n = 43) – patients with bare metal stent (BMS) implanted. CCTA scanning was performed in all patients prior PCI and at 12 months after PCI. The mean CSS at proximal and at distal part of the stented segment and at the level of the minimal lumen area (MLA) was calculated at baseline and at 12 months after BVS placement. Results: CCTA revealed a higher incidence of severe coronary stenosis in group 1 (73%) than in group 2 (30%) (p &amp;lt; 0.0001). Sensibility of visual evaluation for identification of in-stent restenosis on CCTA was increased in BVS group (94%) than in BMS group (76.19%) (p = 0.0006), hence the group 1 had lower incidence of non-diagnostic evaluations. Mean CSS at the stented site was significantly lower at 12 months (1.9 +/- 0.68 Pa) that average CSS at baseline (2.87 +/- 3.08 Pa) (p = 0.0001). CSS analysis showed also a significantly decreased values at proximal level from 3.39 +/- 1.93 Pa at baseline to 1.91 +/- 0.68 Pa at follow up (p &amp;lt; 0.0001), but not a significant decrease at distal part – 1.3+/-0.72 Pa at baseline and 1.59 +/- 0.65 Pa at 12 months follow up (p = 0.9). Conclusions: CCTA is a feasible technique for assessment of luminal changes following BVS implantation. BVS implantation contribute to the improvement of local hemodynamics by restoring physiological pattern of coronary flow, as demonstrated by the computational fluid hemodynamics assessment of coronary circulation.

P114The effect of myocardial bridge on the amount of atherosclerotic plaques and on the local hemodynamic changes

P114The effect of myocardial bridge on the amount of atherosclerotic plaques and on the local hemodynamic changes

The impact of upper-limb position on estimated central blood pressure waveforms.

Pulse wave analysis (PWA) utilizes arm blood pressure (BP) waveforms to estimate aortic waveforms. The accuracy of central BP waveform estimation may be influenced by assessment site local haemodynamics. This study investigated whether local haemodynamic changes, induced via arm tilting ±30° relative to heart level, affect estimated central systolic BP (cSBP) and arterial wave reflection (central augmentation index, cAIx; aortic backward pressure wave, Pb). In 20 healthy adults (26.7 years [SD 5.2], 10 F) brachial BP waveforms were simultaneously recorded on experimental and control arms. The experimental arm was randomly repositioned three times (heart level, -30° heart level, +30° heart level), while the control arm remained fixed at heart level. For the experimental arm, arm repositioning resulted in a large (partial eta-squared > 0.14) effect size (ES) change in SBP (ES = 0.75, P < 0.001), cSBP (ES = 0.81, P < 0.001), and cAIx (ES = 0.75, P = 0.002), but not Pb (ES = 0.06, P = 0.38). In the control arm, cAIx (ES = 0.22, P = 0.013) but not SBP or cSBP significantly changed. Change in experimental arm cSBP was partially explained by brachial systolic blood velocity (P = 0.026) and mean diameter (P = 0.012), while change in cAIx was associated with brachial retrograde blood velocity (P = 0.020) and beta stiffness (P = 0.038). In conclusion, manipulation of assessment site local haemodynamics, including the blood velocity profile and local arterial stiffness, had a large effect on estimated cSBP and cAIx, but not on Pb. These findings do not invalidate PWA devices but do suggest that the accuracy of the estimated aortic pressure waveform is dependent on stable peripheral haemodynamics.

Microfluidic-based laser speckle contrast imaging of erythrocyte flow and magnetic nanoparticle retention in blood

The present study aims to develop a microfluidic system in combination with laser speckle contrast imaging (LSCI) for the study of erythrocyte dynamics under various physiological flow conditions. Microfluidic device was fabricated and red blood cell suspension was introduced at various flow rate controlled by a syringe pump. Relative blood velocity profile in the microfluidic chamber was obtained by LSCI in a real-time manner and correlated well with simulated results by computational fluid dynamics. A close correlation of relative blood velocity, inlet flow rate and blood viscosity were found using this microfluidic-based LSCI system. In addition, our platform also allows the demonstration of spatiotemporal variation of blood flow in response to magnet-induced magnetic nanoparticle (MNP) retention. The flow behaviour of erythrocytes with the presence of MNPs appeared to be closely correlated with the location of the magnet placement. Our microfluidic-based LSCI measurement represents a simple yet controllable experimental model for evaluating the variations in different hemorheological conditions in vitro and has a strong potential as an easy-to-use tool for investigating local MNP retention and hemodynamic changes.

Choroidal volume changes following blow-out fracture repair.

To investigate the serial choroidal volume change following orbital blow-out fracture (BOF) repair. The choroidal volume was measured by optical coherence tomography in patients who underwent BOF repair, preoperatively and postoperatively at 1, 4, 12 and 24weeks. The orbital volume ratio (OVR) was obtained by dividing the orbital volume of the traumatized orbit by that of the contralateral side using three-dimensional computed tomography imaging. The choroidal volume change was compared between both eyes using a linear mixed model. We analyzed the choroidal volume of 11 patients. Choroidal volume showed a trend of slight increase during the immediate postoperative period, and then, choroidal volume decreased abruptly between postoperative 1 to 4weeks (β-coefficient - 0.22, P < 0.001). Choroidal volume also showed gradual decrease between postoperative 4 to 24weeks (β-coefficient - 0.02, P < 0.001). During the study period, there were no significant differences in choroidal volume change between BOF and contralateral unaffected eyes (β-coefficient - 0.20, P = 0.711). The hyperopic refractive errors (β-coefficient 0.27, P = 0.028) and the larger preoperative OVR (β-coefficient 10.37, P = 0.013) were associated with larger choroidal volume. Choroidal volume showed a similar decreasing change following BOF repair between the BOF and the contralateral unaffected eyes. Moreover, choroidal volume of both eyes was associated with the degree of orbital volume expansion due to BOF, suggesting that choroidal volume change after BOF repair was affected not only by trauma-associated local hemodynamic changes but also by systemic influences such as inflammatory response.

Toward longitudinal studies of hemodynamically induced vessel wall remodeling.

Autogenous arteriovenous fistula is the preferred vascular access for hemodialysis, but it has high rates of non-maturation and early failure due to vascular stenosis. Convincing evidence supports a key role of local hemodynamics in vascular remodeling, suggesting that unsteady and disturbed flow conditions may be related to stenosis formation in arteriovenous fistula. The purpose of our study was to explore the feasibility of coupling contrast-free magnetic resonance imaging and computational fluid dynamics in longitudinal studies to identify the role of local hemodynamic changes over time in inducing vessel wall remodeling in arteriovenous fistula. We acquired contrast-free magnetic resonance imaging of arm vasculature at 1 week and 6 weeks after arteriovenous fistula creation in a 72-year-old patient. We then generated three-dimensional models and evaluated lumen cross-sectional area of arteriovenous fistula limbs. We performed high-resolution computational fluid dynamics to evaluate changes in local hemodynamics over time. Our contrast-free magnetic resonance imaging protocol provided good quality images in a short scan duration. We observed a homogeneous dilatation in the proximal artery, while there was a more pronounced lumen dilatation in the venous outflow as compared to a limited dilatation in the juxta-anastomotic vein. Furthermore, we observed a slight stabilization of the flow pattern over time, suggesting that vascular outward remodeling accommodates the flow to a more helicoidally phenotype. Coupling contrast-free magnetic resonance imaging and high-resolution computational fluid dynamics represents a promising approach to shed more light in the mechanisms of vascular remodeling and can be used for prospective clinical investigations aimed at identifying critical hemodynamic factors contributing to arteriovenous fistula failure.

Functional brain mapping using optical imaging of intrinsic signals and simultaneous high-resolution cortical electrophysiology with a flexible, transparent microelectrode array

Intrinsic optical signal imaging (IOSI) records tiny changes in optical reflection of the exposed cortical surface due to neuronal activation related local hemodynamic changes. Cortical electrophysiology performed in the very same visual cortical area may provide additional insight into the connectivity between functional domains. Our aim is to investigate the simultaneous use of IOSI and μECoG (micro-electrocorticography) techniques by introducing a transparent polymer based subdural microelectrode array into the optical recording chamber used for in vivo functional mapping experiments in anaesthetized cats. To demonstrate the feasibility of the combined optical-electrical recording, we have run several stimulus protocols and measured the evoked optical and electrical responses of the primary visual cortex in a synchronized manner. Optical quality of IOSI signals (609 nm) was also evaluated without the ECoG microelectrode as a reference. During the visual stimulus, local field potential on a 32-channel of the ECoG was simultaneously recorded and evaluated. Specific power density distribution was detected in wide band frequency range, and the distribution of a unique 80 Hz oscillation in gamma range occurring only as a response to stimuli was also found. This is the first demonstration of microelectrocorticography using PI/ITO/PI based microelectrode arrays in combination with in vivo IOSI.