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ISSN / EISSN : 1073-9688 / 1549-8719
Published by: Wiley-Blackwell (10.1111)
Total articles ≅ 2,396
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, Olivia N. Kunkel, Dryden R. Baumfalk, Mikaela E. Simon, Kiana M. Schulze, Wei‐Wen Hsu, Judy Muller‐Delp, David C. Poole, Bradley J. Behnke
Published: 1 September 2021
Prolonged mechanical ventilation (MV) (≥6 h) results in large, time-dependent reductions in diaphragmatic blood flow and shear stress. We tested the hypothesis that MV would impair the structural and material properties (i.e. increased stress/stretch relation and/or circumferential stretch) of first-order arterioles (1A) from the medial costal diaphragm. Methods Shear stress was estimated from isolated arterioles and prior blood flow data from the diaphragm during spontaneous breathing (SB) and prolonged MV (6 h MV). Thereafter, female Sprague-Dawley rats (~5 mo) were randomly divided into two groups, SB (n = 6) and 6 h MV (n = 6). Following SB and 6 h MV, 1A medial costal diaphragm arterioles were isolated, cannulated, and subjected to step-wise (0-140 cmH2O) increases in intraluminal pressure in calcium-free Ringer’s solution. Inner diameter and wall thickness were measured at each pressure step and used to calculate wall: lumen ratio, Cauchy-stress, and circumferential stretch. Results Compared to SB, there was a ~90% reduction in arteriolar shear-stress with prolonged MV (9 ± 2 versus 78 ± 20 dynes cm-2; p≤0.05). In the unloaded condition (0 cmH2O), the arteriolar intraluminal diameter was reduced (37 ± 8 versus 79 ± 13 μm) and wall: lumen ratio was increased (120 ± 18 versus 46 ± 10 %) compared to SB (p≤0.05). There were no differences in the passive diameter responses or the circumferential stress/stretch relationship between groups (p>0.05), but at each pressure step, circumferential stretch was increased with 6 h MV versus SB (p≤0.05). Conclusion During prolonged MV, medial costal diaphragm arteriolar shear stress is severely diminished. Despite no change in the material behavior (stress/stretch), prolonged MV resulted in altered structural and mechanical properties (i.e. elevated circumferential stretch) of medial costal diaphragm arterioles. This provides important novel mechanistic insights into the impaired diaphragm blood flow capacity and vascular dysfunction following prolonged MV.
Caitlin R. Francis,
Published: 20 August 2021
Objectives Vesicular trafficking dictates protein localization, functional activity, and half-life, providing a critically important regulatory step in tissue development; however, there is little information detailing endothelial-specific trafficking signatures. This is due, in part, to limitations in visualizing trafficking events in endothelial tissues. Our aim in this investigation was to explore the use of a 3-dimensional (3D) in vitro sprouting model to image endothelial membrane trafficking events. Methods Endothelial cells were challenged to grow sprouts in a fibrin bead assay. Thereafter, spouts were transfected with fluorescent proteins and stained for various cell markers. Sprouts were then imaged for trafficking events using live and fixed-cell microscopy. Results Our results demonstrate that fibrin bead sprouts have a strong apicobasal polarity marked by apical localization of proteins moesin and podocalyxin. Comparison of trafficking mediators Rab27a and Rab35 between 3D sprouts and 2D culture showed that vesicular carriers can be imaged at high resolution, exhibiting proper membrane polarity solely in 3D sprouts. Lastly, we imaged exocytic events of von Willebrand Factor and demonstrated a distinct imaging advantage for monitoring secretion events in 3D sprouts as compared with 2D culture. Conclusions Our results establish that the fibrin bead sprouting assay is well-suited for imaging of trafficking events during angiogenic growth.
, James Randall Patrinely, , Michael Byrne,
Published: 19 August 2021
Objective To develop a guideline that reliably identifies cutaneous adherent and rolling leukocytes from mimicking scenarios via in vivo reflectance confocal videomicroscopy. Methods We used a clinical reflectance confocal microscope, the VivaScope 1500, to acquire 1522 videos of the upper dermal microcirculation from 12 healthy subjects and 60 patients after allogeneic hematopoietic cell transplantation. Blinded to clinical information, two trained raters independently counted the number of adherent and rolling leukocytes in 88 videos. Based on discrepancies in the initial assessments, we developed a guideline to identify both types of leukocyte-endothelial interactions via a modified Delphi method (without anonymity). To test the guideline’s ability to improve the inter-rater reliability, the two raters assessed the remaining 1434 videos by using the guideline. Results We demonstrate a guideline that consists of definitions, a step-by-step flowchart, and corresponding visuals of adherent and rolling leukocytes and mimicking scenarios. The guideline improved the inter-rater reliability of the manual assessment of both interactions. The intraclass correlation coefficient (ICC) of adherent leukocyte counts increased from 0.056 (95% confidence interval: 0-0.236, n=88 videos, N=10 subjects) to 0.791 (0.770-0.809, n=1434, N=67). The ICC of rolling leukocyte counts increased from 0.385 (0.191-0.550, n=88, N=10) to 0.626 (0.593-0.657, n=1434, N=67). Intra-rater ICC post-guideline was 0.953 (0.886-0.981, n=20, N=12) and 0.956 (0.894-0.983, n=20, N=12) for adherent and rolling, respectively. Conclusion The guideline aids in the manual identification of adherent and rolling leukocytes via in vivo reflectance confocal videomicroscopy.
Bing Wang, Youming Sheng, Yuan Li, , Jian Zhang, Ailing Li, , Honggang Zhang,
Published: 5 August 2021
Objective The contractile behavior of collecting lymphatic vessels occurs in essential hypertension in response to homeostasis, suggesting a possible role for microcirculation. We aimed to clarify the nature of the lymphatic microcirculation profile in spontaneously hypertensive rats (SHRs) and normotensive controls. Methods The vasomotion of collecting lymphatic vessels in eight- and thirteen-week-old SHRs and age-matched Wistar-Kyoto rats (WKYs, n = 4 per group) was visualized by intravital video and VasTrack. The lymphatic vasomotion profile (frequency and amplitude) and contractile parameters (contraction fraction and total contractility activity index) were compared. Plasma nitrite/nitrate levels were assessed by the Griess reaction, and plasma endothelin-1 was measured by enzyme-linked immunosorbent assay. Results WKYs and SHRs differed in the vasomotion of collecting lymphatic vessels. Both eight- and thirteen-week-old WKYs revealed a high-amplitude pumping pattern, whereas a low-amplitude pattern was observed in SHRs. Moreover, compared with age-matched WKYs, SHRs exhibited deteriorated output and reflux capability and lost the ability to regulate collecting lymphatic vasomotion. Additionally, the chemistry complements the microcirculatory lymphatic profile as demonstrated by an increase in plasma nitrite, nitrate, and endothelin-1 in SHRs. ET-1 inhibitor meliorated the lymphatic contractile capability in SHRs partially through regulating frequency of lymphatic vasomotion. Conclusions We used an intravital lymphatic imaging system to observe that SHRs exhibit an impaired collecting lymphatic vasomotion profile and deteriorated contractility and reflux.
Yu Zhang, Jianfeng Zeng, Xiaoqian He, Weidong Cao, Xiaopeng Peng,
Published: 9 July 2021
Background Pulsatile flow protects vital organ function and improves microcirculatory perfusion during extracorporeal membrane oxygenation (ECMO). Studies revealed that pulsatile shear stress plays a vital role in microcirculatory function and integrity. The objective of this study was to investigate how pulsatility affects wall shear stress and endothelial glycocalyx components during ECMO. Methods Using the i-Cor system, sixteen canine ECMO models were randomly allocated into the pulsatile or the non-pulsatile group (eight canines for each). Hemodynamic parameters, peak wall shear stress (PWSS), serum concentration of syndecan-1, and heparan sulfate were measured at different time points during ECMO. Pulsatile shear stress experiments were also performed in endothelial cells exposed to different magnitudes of pulsatility (five plates for each condition), with cell viability, the expressions of syndecan-1, and endothelial-to-mesenchymal transformation (EndMT) markers analyzed. Results The pulsatile flow generated more surplus hemodynamic energy and preserved higher PWSS during ECMO. Serum concentrations of both syndecan-1 and heparan sulfate were negatively correlated with PWSS, and significantly lower levels were observed in the pulsatile group. Besides, non-pulsatility triggered EndMT and endothelial cells exposed to low pulsatility had the lowest possibility of EndMT. Conclusion The maintenance of the PWSS by pulsatility during ECMO possesses beneficial effects on glycocalyx integrity. Moreover, pulsatility prevents EndMT in endothelial cells, and low pulsatility exhibits the best protective effects. The augmentation of pulsatility may be a plausible future direction to improve the clinical outcome in ECMO.
, Ricardo Cortez,
Published: 30 June 2021
by 10.1111
Objective Chronic glomerular hypertension is associated with glomerular injury and sclerosis, however the mechanism by which increases in pressure damage glomerular podocytes remains unclear. We tested the hypothesis that increases in glomerular pressure may deleteriously affect podocyte structural integrity by increasing the strain of the glomerular capillary walls, and that glomerular capillary wall strain may play a significant role in the perpetuation of glomerular injury in disease states that are associated with glomerular hypertension. Methods We developed an anatomically accurate mathematical model of a compliant, filtering rat glomerulus to quantify the strain of the glomerular capillary walls in a remnant glomerulus of the 5/6-nephrectomized rat model of chronic kidney disease. In terms of estimating the mechanical stresses and strains in the glomerular capillaries, this mathematical model is a substantial improvement over previous models which do not consider pressure-induced alterations in glomerular capillary diameters in distributing plasma and erythrocytes throughout the network. Results Using previously reported data from experiments measuring the change of glomerular volume as a function of perfusion pressure, we estimated the Young’s modulus of the glomerular capillary walls in both control and 5/6-nephrectomized conditions. We found that in 5/6-nephrectomized conditions, the Young’s modulus increased to 8.6 MPa from 7.8 MPa in control conditions, but the compliance of the capillaries increased in 5/6-nephrectomized conditions due to a 23.3% increase in the glomerular capillary diameters. We found that glomerular capillary wall strain was increased approximately 3-fold in 5/6-nephrectomized conditions over control, which may deleteriously affect both mesangial cells and podocytes. The magnitudes of strain in model simulations of 5/6-nephrectomized conditions were consistent with magnitudes of strain that elicit podocyte hypertrophy and actin cytoskeleton reorganization in vitro. Conclusions Our findings indicate that glomerular capillary wall strain may deleteriously affect podocytes directly, as well as act in concert with other mechanical changes and environmental factors inherent to the in vivo setting to potentiate glomerular injury in severe renoprival conditions.
Sunggi Noh, Seungyong Lee, Sophie Green,
Published: 21 June 2021
Objectives The ability to regulate skeletal blood flow is critical for the maintenance of bone. The myogenic response is essential for regulating tissue blood flow. Myogenic responsiveness in bone marrow arterioles has not yet been determined. Furthermore, the literature is disparate regarding intramedullary pressures (IMP) within bone. The purposes of this study were to (1) determine whether bone marrow arterioles have myogenic activity and (2) assess if the autoregulatory zone corresponds with IMP. Also, this study provides detailed methodology on dissecting and isolating bone marrow arterioles for functional assessment. Methods Experiment 1: Femoral shafts of female Long Evans rats were catheterized to assess in vivo IMP. Experiment 2: Bone marrow arterioles from female Long Evans rats were cannulated. Active and passive myogenic responses were determined. Results In vivo intramedullary pressure averaged 32 ± 3 mmHg, intramedullary pulse pressure averaged 5.28 ± 0.03 mmHg, and the mean maximal diameter and wall thickness of the bone marrow arterioles were 96 ± 7 µm and 18 ± 2 µm, respectively. An active myogenic response was observed and differed (p < .001) from the passive curve. Conclusion Bone marrow arterioles have myogenic responsiveness and the autoregulatory zone corresponded with the range of IMP (15–51 mmHg) within the femoral diaphysis of conscious animals.
Khalil Ghasemi Falavarjani, , Hamid Riazi‐Esfahani, Pasha Anvari, Abbas Habibi, Maryam Ashraf Khorasani, Esrafil Shad
Published: 9 June 2021
Objective To evaluate the distribution of capillary non-perfusion (CNP) in superficial and deep capillary plexuses (SCP and DCP) in eyes with diabetic retinopathy (DR). Methods In this retrospective case series, macular optical coherence tomography angiography (OCTA) images were obtained from eyes with DR without diabetic macular edema. The area of CNP in SCP and DCP was delineated using an automated approach after excluding the foveal avascular zone and major retinal vessels. The distribution and spatial correlation of the CNP in each layer was analyzed. Results Forty-three eyes of 27 patients with diabetic retinopathy with a mean age of 59.10± 9.05 years were included. The mean CNP area in SCP was statistically significantly higher than DCP (0.722± 0.437 mm2 vs 0.184± 0.145 mm2, respectively, P<0.001). There was a statistically significant association between mean BCVA (0.28±0.21 logMAR) and CNP area in DCP (P=0.01). After automated subtraction of CNP areas in DCP from SCP, 25.43±15.05 % of CNP areas in the DCP had co-localized CNP areas in SCP. The CNP percentage was statistically significantly different between the concentric rings on foveal center, both in SCP and DCP (both P<0.001) showing a decreasing trend from the outer ring toward the center. Conclusion In DR, SCP is more ischemic than DCP. This is in contrast to the previously described oxygenation dependent ischemic cascade following acute retinal vascular occlusions. This study provides further insight into the retinal ischemia in DR.
Jie Yin, Shaoshen Wang, Yang Liu, Junhong Chen, ,
Published: 20 May 2021
Recently, accumulating evidence has highlighted the role of endothelial dysfunction in COVID-19 progression. Coronary microvascular dysfunction (CMD) plays a pivotal role in cardiovascular disease (CVD) and CVD-related risk factors (eg, age, gender, hypertension, diabetes mellitus, and obesity). Equally, these are also risk factors for COVID-19. The purpose of this review was to explore CMD pathophysiology in COVID-19, based on recent evidence. COVID-19 mechanisms were reviewed in terms of imbalanced renin-angiotensin-aldosterone-systems (RAAS), systemic inflammation and immune responses, endothelial dysfunction, and coagulatory disorders. Based on these mechanisms, we addressed CMD pathophysiology within the context of COVID-19, from five perspectives. The first was the disarrangement of local RAAS and Kallikrein-kinin-systems attributable to SARS-Cov-2 entry, and the concomitant decrease in coronary microvascular endothelial angiotensin I converting enzyme 2 (ACE2) levels. The second was related to coronary microvascular obstruction, induced by COVID-19-associated systemic hyper-inflammation and pro-thrombotic state. The third was focused on how pneumonia/acute respiratory distress syndrome (ARDS)-related systemic hypoxia elicited oxidative stress in coronary microvessels and cardiac sympathetic nerve activation. Fourthly, we discussed how autonomic nerve dysfunction mediated by COVID-19-associated mental, physical, or physiological factors could elicit changes in coronary blood flow, resulting in CMD in COVID-19 patients. Finally, we analyzed reciprocity between the coronary microvascular endothelium and perivascular cellular structures due to viremia, SARS-CoV-2 dissemination, and systemic inflammation. These mechanisms may function either consecutively or intermittently, finally culminating in CMD-mediated cardiovascular symptoms in COVID-19 patients. However, the underlying molecular pathogenesis remains to be clarified.
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