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Acute injury of skeletal muscle disrupts myofibres, microvessels and motor innervation. Myofibre regeneration is well characterized, however its relationship with the regeneration of microvessels and motor nerves is undefined. Endothelial cell (EC) ephrin‐B2 (Efnb2) is required for angiogenesis during embryonic development and promotes neurovascular regeneration in the adult. We hypothesized that, following acute injury to skeletal muscle, loss of EC Efnb2 would impair microvascular regeneration and the recovery of neuromuscular junction (NMJ) integrity. Mice (aged 3–6 months) were bred for EC‐specific conditional knockout (CKO) of Efnb2 following tamoxifen injection with non‐injected CKO mice as controls (CON). The gluteus maximus, tibialis anterior or extensor digitorum longus muscle was then injured with local injection of BaCl2. Intravascular staining with wheat germ agglutinin revealed diminished capillary area in the gluteus maximus of CKO vs. CON at 5 days post‐injury (dpi); both recovered to uninjured (0 dpi) level by 10 dpi. At 0 dpi, tibialis anterior isometric force of CKO was less than CON. At 10 dpi, isometric force was reduced by half in both groups. During intermittent contractions (75 Hz, 330 ms s–1, 120 s), isometric force fell during indirect (sciatic nerve) stimulation whereas force was maintained during direct (electrical field) stimulation of myofibres. Neuromuscular transmission failure correlated with perturbed presynaptic (terminal Schwann cells) and postsynaptic (nicotinic acetylcholine receptors) NMJ morphology in CKO. Resident satellite cell number on extensor digitorum longus myofibres did not differ between groups. Following acute injury of skeletal muscle, loss of Efnb2 in ECs delays capillary regeneration and attenuates recovery of NMJ structure and function. Key points: The relationship between microvascular regeneration and motor nerve regeneration following skeletal muscle injury is undefined. Expression of Efnb2 in endothelial cells (ECs) is essential to vascular development and promotes neurovascular regeneration in the adult.To test the hypothesis that EfnB2 in ECs is required for microvascular regeneration and myofibre reinnervation, we induced conditional knockout of Efnb2 in ECs of mice. Acute injury was then induced by BaCl2 injection into gluteus maximus, tibialis anterior or extensor digitorum longus (EDL) muscle.Capillary regeneration was reduced at 5 days post‐injury (dpi) in gluteus maximus of conditional knockout vs. controls; at 10 dpi, neither differed from uninjured. Nerve stimulation revealed neuromuscular transmission failure in tibialis anterior with perturbed neuromuscular junction structure. Resident satellite cell number on EDL myofibres did not differ between groups.Conditional knockout of EC Efnb2 delays capillary regeneration and attenuates recovery of neuromuscular junction structure and function. [ABSTRACT FROM AUTHOR]

Introduction: Endurance exercise at altitude can increase cardiac output and pulmonary vascular pressure to levels that may exceed the stress tolerability of the alveolar--capillary unit. This study examined the effect of ultramarathon trail racing at different altitudes (ranging from <1000 m to between 1500 and 2700 m) on alveolar--capillary recruitment and lung diffusion. Methods: Cardiac and lung function were examined before and after an ultramarathon in 67 runners (age: 41 ± 9 yr, bodymass index: 23 ± 2 kg⋅m-2, 10 females), and following 12-24 h of recovery in a subset (n = 27). Cardiac biomarkers (cTnI and BNP) were assessed from whole blood, whereas lung fluid accumulation (comet tails), stroke volume (SV), and cardiac output (Q)were quantified via echocardiography. Lung diffusing capacity for carbonmonoxide (DLco) and its components, alveolar membrane conductance (Dm) and capillary blood volume (Vc), were determined via a single-breath method at rest and during three stages of submaximal semirecumbent cycling (20, 30, and 40W). Results:Average race time was 25 ± 12 h. From pre- to post-race, there was an increase in cardiac biomarkers (cTnI: 0.04 ± 0.02 vs 0.13 ± 0.03 ng⋅mL-1,BNP: 20 ± 2 vs 112 ± 21 pg⋅mL-1; P < 0.01) and lung comet tails (2 ± 1 vs 7 ± 6, P < 0.01), a decrease in resting and exercise SV (76 ± 2 vs 69 ± 2 mL, 40 W: 93 ± 2 vs 88 ± 2 mL; P < 0.01), and an elevation in Q at rest (4.1 ± 0.1 vs 4.6 ± 0.2 L⋅min-1, P < 0.01; 40 W: 7.3 ± 0.2 vs 7.4 ± 0.3 L⋅min-1, P = 0.899). Resting DLco and Vc decreased after the race ( P < 0.01), whereas Dm was unchanged ( P = 0.465); however, during the three stages of exercise, DLco, Vc, and Dm were all reduced from pre- to post-race (40 W: 36.3 ± 0.9 vs 33.0 ± 0.8 mL⋅min-1⋅mm Hg-1, 83 ± 3 vs 73 ± 2 mL, 186 ± 6 vs 170 ± 7 mL⋅min-1⋅mm Hg-1, respectively; P < 0.01). When corrected for alveolar volume and Q, DLco decreased from pre- to post-race ( P < 0.01), and changes in DLco were similar for all ultramarathon events ( P > 0.05). Conclusions: Competing in an ultramarathon leads to a transient increase in cardiac injury biomarkers, mild lung-fluid accumulation, and impairments in lung diffusion. Reductions in DLco are predominantly caused by a reduced Vc and possible pulmonary capillary de-recruitment at rest. However, impairments in alveolar--capillary recruitment and Dm both contribute to a fall in exertional DLco following an ultramarathon. Perturbations in lung diffusion were evident across a range of event distances and varying environmental exposures. [ABSTRACT FROM AUTHOR]

The article evaluates the role of rapid red blood cell (RBC) transit times through pulmonary capillaries in exercise-induced pulmonary diffusion limitation, finding it to be a minor factor. It also discusses the impact of endurance training on RBC transit times, the relationship between pulmonary capillary and whole lung RBC transit times, and the effectiveness of existing research in addressing concerns about diffusion limitation during high-intensity exercise.

The article critiques the idea that rapid red blood cell (RBC) transit times through pulmonary capillaries contribute significantly to exercise-induced arterial hypoxemia (EIAH), citing evidence from both animal and human studies to refute this claim. It also discusses the limitations of the Multiple Inert Gas Elimination Technique (MIGET) in pinpointing the exact causes of diffusion limitations and highlights the role of endurance training in stabilizing pulmonary capillary blood volume.

The article critiques Dr. Zavorsky's response to previous work on exercise-induced pulmonary diffusion limitation, emphasizing that capillary red cell transit time (CTT) plays a significant role in this phenomenon. It also discusses the need for more research on CTT heterogeneity, the relationship between CTT and diffusion limitation, and the limitations of current methods for evaluating these factors.

Background: Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery. Methods: Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified. Results: Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p < 0.001). The occurrences of skin mottling were higher in hypotension population and shock population, reaching 5.6% and 15.7%, respectively. The AUROC for SMS to identify peripheral hypoperfusion was 0.64, 0.68, and 0.81 in the overall, hypotension, and shock populations, respectively. The optimal SMS threshold was 1, which corresponded to specificities of 98, 97 and 91 and sensitivities of 29, 38 and 67 in the three populations (overall, hypotension and shock). The correlation of UO, lactate, CRT and vasopressor dose with SMS was significant, among them, UO and CRT were identified as two major factors associated with the presence of skin mottling. Conclusion: In critically ill patients following cardiac surgery, SMS is a very specific yet less sensitive parameter for detecting peripheral tissue hypoperfusion. [ABSTRACT FROM AUTHOR]

Background: Skin mottling as a clinical perfusion marker in septic shock is significantly associated with severity and outcome in white-skinned population and its validity as a clinical sign in dark-skinned population is not known. The objectives of this study were to evaluate mottling in septic shock in the Indian ethnic population who has different skin color as compared to the white-skinned population and to assess mottling as an outcome predictor with capillary refill time (CRT) and other biochemical parameters which are the established clinical markers of perfusion in septic shock. Materials and methods: We conducted a prospective observational study of patients with skin color categories 21-34 on the von Luschan scale or Fitzprick type IV-VI who had septic shock needing a high dose of norepinephrine ≥0.2 µg/kg/min after fluid optimization. The study was conducted in a mixed medical-surgical ICU over 12 months. Two blinded experts (a Dermatologist and a plastic surgeon) independently classified the skin type, validated the occurrence of mottling, and scored mottling in our patients. We recorded the demographics, hemodynamic variables, and mottling score and observed the incidence of mottling and its correlation with predictors of the severity of septic shock. We also compared CRT, arterial lactate, central venous oxygen saturation, and venoarterial PCO2 gap with occurrence of mottling in septic shock patients. Results: We included 108 patients with age 61 ± 16 years. Mean Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores at enrolment were 10.3-21.9, respectively. Incidence of mottling was 20.3% (22/108). CRT >3 seconds was observed in 50.9% (55/108). Development of mottling was significantly associated with 90-day mortality; 20/22 (90.9%) patients died in the mottling group versus 58/86 (65.1%) in the non-mottling group (p = 0.028). Capillary refill time >3 seconds did not corelate with mortality; 40/55 (72.7%) Patients with CRT >3 seconds died versus 32/53 (60.4%) patients died in CRT ≤3 seconds group. Occurrence of mottling could predict mortality; positive predictive value of 90.9% which was comparable to positive predictive value of lactate levels >4 mmol/L, i.e., 94.1%. Conclusion: The incidence of mottling in septic shock is much less in patients of Indian ethnicity with brown skin color than in white-skinned population. Occurrence of mottling and not delayed CRT, is a better predictor of outcome in this setting. [ABSTRACT FROM AUTHOR]

Objectives Nailfold capillaroscopy is key to timely diagnosis of SSc, but is often not used in rheumatology clinics because the images are difficult to interpret. We aimed to develop and validate a fully automated image analysis system to fill this gap. Methods We mimicked the image interpretation strategies of SSc experts, using deep learning networks to detect each capillary in the distal row of vessels and make morphological measurements. We combined measurements from multiple fingers to give a subject-level probability of SSc. We trained the system using high-resolution images from 111 subjects (group A) and tested on images from subjects not in the training set: 132 imaged at high-resolution (group B); 66 imaged with a low-cost digital microscope (group C). Roughly half of each group had confirmed SSc, and half were healthy controls or had primary RP ('normal'). We also estimated the performance of SSc experts. Results We compared automated SSc probabilities with the known clinical status of patients (SSc versus 'normal'), generating receiver operating characteristic curves (ROCs). For group B, the area under the ROC (AUC) was 97% (94–99%) [median (90% CI)], with equal sensitivity/specificity 91% (86–95%). For group C, the AUC was 95% (88–99%), with equal sensitivity/specificity 89% (82–95%). SSc expert consensus achieved sensitivity 82% and specificity 73%. Conclusion Fully automated analysis using deep learning can achieve diagnostic performance at least as good as SSc experts, and is sufficiently robust to work with low-cost digital microscope images. [ABSTRACT FROM AUTHOR]

Multiple tissue perfusion markers are described to guide therapy in critically ill pediatric patients undergoing congenital heart surgery. Given the advantages of capillary refill time, our goal is to determine its predictive capacity for mortality and postoperative extracorporeal oxygenation requirements in congenital heart surgery and compare it to serum lactate. We conducted a prospective cohort observational study in a single high-complexity university hospital. Serum lactate and capillary refill time were measured at five predetermined time points: preoperative, immediate postoperative, 6, 12, and 24 h after the surgery. Prolonged immediate postoperative, 6 h, and 12 h capillary refill time measurements turned out to be independent risk factors for both outcomes. The capillary refill time area under the curve ranged between 0.70 and 0.80, while the serum lactate resulted between 0.79 and 0.92 for both outcomes. Both tissue perfusion markers resulted in mortality and extracorporeal oxygenation requirement predictors. Given the advantages of capillary refill time over serum lactate, a monitoring strategy including these two perfusion markers should be considered for congenital heart surgeries. [ABSTRACT FROM AUTHOR]

Background: Capillary Refill Time (CRT) is a marker of peripheral perfusion usually performed at fingertip; however, its evaluation at other sites/position may be advantageous. Moreover, arm position during CRT assessment has not been fully standardized. Methods: We performed a pilot prospective observational study in 82 healthy volunteers. CRT was assessed: a) in standard position with participants in semi-recumbent position; b) at 30° forearm elevation, c and d) at earlobe site in semi-recumbent and supine position. Bland–Altman analysis was performed to calculate bias and limits of agreement (LoA). Correlation was investigated with Pearson test. Results: Standard finger CRT values (1.04 s [0.80;1.39]) were similar to the earlobe semi-recumbent ones (1.10 s [0.90;1.26]; p = 0.52), with Bias 0.02 ± 0.18 s (LoA -0.33;0.37); correlation was weak but significant (r = 0.28 [0.7;0.47]; p = 0.01). Conversely, standard finger CRT was significantly longer than earlobe supine CRT (0.88 s [0.75;1.06]; p < 0.001) with Bias 0.22 ± 0.4 s (LoA -0.56;1.0), and no correlation (r = 0,12 [-0,09;0,33]; p = 0.27]. As compared with standard finger CRT, measurement with 30° forearm elevation was significantly longer (1.17 s [0.93;1.41] p = 0.03), with Bias -0.07 ± 0.3 s (LoA -0.61;0.47) and with a significant correlation of moderate degree (r = 0.67 [0.53;0.77]; p < 0.001). Conclusions: In healthy volunteers, the elevation of the forearm significantly prolongs CRT values. CRT measured at the earlobe in semi-recumbent position may represent a valid surrogate when access to the finger is not feasible, whilst earlobe CRT measured in supine position yields different results. Research is needed in critically ill patients to evaluate accuracy and precision at different sites/positions. [ABSTRACT FROM AUTHOR]

Objectives To identify barriers to the use of nailfold capillaroscopy as a diagnostic tool for patients presenting with Raynaud's phenomenon in UK rheumatology centres and to obtain rheumatologists' views on a proposed internet-based standardized system for clinical reporting of nailfold capillaroscopy images. Methods An online survey was developed using expert opinion from clinicians, scientists and health service researchers. The survey was piloted and sent to UK-based rheumatologists using established electronic mailing lists between October 2020 and March 2021. Survey data were analysed using descriptive statistics. Results A total of 104 rheumatologists representing rheumatology centres across the UK responded to the survey. Wide variations in terms of workloads and practices were described. Thirty-four (33%) respondents reported using nailfold capillaroscopy only at their own centre, 33 (32%) referred to other centres, 9 (9%) did both and 28 (27%) did not use capillaroscopy at all. Of the 43 respondents using capillaroscopy on site, 25 (58%) used either a dermatoscope or universal serial bus microscope and 9 (21%) used videocapillaroscopy. Among the 61 respondents not undertaking capillaroscopy on site, barriers included lack of equipment (85%), lack of experience in acquiring images (69%) and lack of expertise in interpreting images (67%). Sixty-six respondents (63%) expressed interest in an internet-based, standardized automated system for reporting images. Conclusion Most UK rheumatologists currently do not perform nailfold capillaroscopy on site. An internet-based nailfold capillaroscopy system for use with low-cost microscopes as well as with videocapillaroscopy could help increase uptake of capillaroscopy and thereby facilitate early diagnosis of SSc across the UK. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we aimed to investigate capillary vessel diameters and structural changes of capillaries by using nailfold video capillaroscopy (NVC) in patients with polycythemia vera (PV). Patients and methods: This cross-sectional study included a total of 24 patients (19 males, 5 females; mean age: 59.8±12.9 years; range, 50.2 to 68 years) who were diagnosed with PV and 15 healthy controls (11 males, 4 females; mean age: 40.7±5.1 years; range, 36 to 44 years) between June 2016 and February 2017. Nailfold video capillaroscopy was performed by an experienced rheumatologist who was blinded to clinical data. The apical, arterial, and venous limb diameters of capillaries were measured and microvascular changes of capillaries were scored. Results: When capillaries were evaluated in terms of morphological structures, giant capillary was detected in 67% of the patients with PV and 0% in the control group (p<0.05). The arterial, venous, and apical diameters of the capillaries were significantly higher in the patients with PV compared to the control group (p<0.001). Conclusion: The presence of giant capillaries and the marked increase of arterial, venous, and apical diameters of capillaries seem to be related to PV. As it additionally plays an important role in diagnosis, prognosis, and treatment monitoring of certain diseases, capillaroscopy can be considered to be a promising microcirculation biomarker. [ABSTRACT FROM AUTHOR]

Purpose: No standardized execution or evidence demonstrates the area of the digit giving the most accurate capillary refill time (CRT). This study investigated the reliability and validity of CRT, and the relative merits of areas where the test could be performed. Methods: In all, 127 healthy volunteers were assessed for normal CRT at the fingernail, lateral paronychia, and proximal and distal pulps of the index finger. The predictive validity of the CRT for the diagnosis of compromised vascular perfusion was also investigated on 24 subjects, using an inflated tourniquet. Three raters assessed interobserver reliability. Results: The mean fingernail, lateral paronychia, proximal pulp, and distal pulp CRTs were 1.93, 1.78, 1.70, and 1.57 s, respectively. The tourniquet and non-tourniquet results demonstrated significant mean differences; however, the fingernail showed a subtle difference (1.22 s) compared with the proximal pulp (4.46 s). The CRT interobserver reliability was fair at the fingernail (intraclass correlation coefficient [ICC] = 0.51), but very poor in occluded limbs (ICC = 0.13). At the lateral paronychia and finger pulp, the interobserver reliability was reasonable (ICC = 0.75–0.81 [non-tourniquet] vs 0.62–0.68 [tourniquet]). In a receiver-operating characteristic curve analysis, the proximal pulp demonstrated better discrimination (area under the curve = 0.93, 95% CI 0.89–0.97, p < 0.0001); the best cutoff point was calculated to be 3 s at the proximal pulp. Conclusions: CRT use at appropriate areas is reliable. The most dependable site is the finger pulp, and the proposed cutoff is 3 s. [ABSTRACT FROM AUTHOR]

Objective: Systemic sclerosis (SSc) is a progressive connective tissue disorder that features vascular injury and persistent fibrosis with an autoimmune background. The hypoxic state at the capillary caused by SSc can be assessed with several methods. This study thus investigated the capillary refill time (CRT) effectivity in evaluating peripheral circulation in SSc patients. Methods: This prospective, case-control study was conducted with SSc patients and gender and age-matched healthy controls. The CRT measurements were performed by a rheumatologist unaware of patients' records with a smartphone camera in the optimized test ambiance. A video processing software was then applied for the captured videos. Results: 61 patients with SSc and 60 controls participated in this study. According to disease involvement, the patients were then divided into diffuse cutaneous SSc (dSSc) and limited cutaneous SSc. Mainly, CRT was prolonged in the patient group than in the control group. CRT was also prolonged in patients with pathological capillaroscopy patterns in the nail fold capillaroscopy (NFC), below 50 years old, or whose disease duration was over three years. Per disease involvement, patients in the dSSc group with pathologic NFC had prolonged CRT results and higher pulmonary artery pressure levels. The use of CRT for NFC positivity in patients with SSc was practicable (AUC: 0.717;95% CI 0.714-0.942; 83.95% accuracy; 67.9% sensitivity, 100% specificity, 100% positive predictive value, 21.7% negative predictive value, P=0.015). Conclusions: CRT is markedly prolonged in patients with SSc. Evaluating CRT with the NFC positivity may provide pulmonary progression predictable, notably in dSSc patients. [ABSTRACT FROM AUTHOR]

Objectives To investigate subclinical and clinical abnormalities in retinal and choroidal vascular plexuses in patients with SSc by means of optical coherence tomography angiography (OCT-A). Methods A total of 20 consecutive SSc patients were recruited and compared with 20 healthy subjects. Quantitative analysis of vessel density (VD), choriocapillaris plexus flow index (CCP-FI) and choroidal vascularity index were performed on OCT-A images in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and CCP for all patients. Images were further reviewed by two independent readers for the assessment of qualitative abnormalities, including tortuosity, rarefaction areas, megacapillaries and macular-foveal capillaries. Results The DCP-VD in the whole scan and in the perifoveal, superior, inferior, nasal and temporal regions was significantly lower in the SSc group. The CCP-FI was significantly higher in SSc patients. When comparing SSc patients with and without digital ulcers, significantly decreased SCP-VD was demonstrated in the whole, perifoveal, superior, inferior, temporal and nasal regions. No difference in any of the OCT-A parameters was observed when comparing patients with and without interstitial lung disease. Qualitative analysis of OCT-A revealed at least one abnormality in 95% of patients. Conclusion We showed the ability of OCT-A to disclose early ocular vascular abnormalities in patients with SSc. Our results may represent a hypothesis-generating basis for exploring the potential role of OCT-A in diagnosis, monitoring and prognosis stratification in SSc. [ABSTRACT FROM AUTHOR]

Background: Mortality in surgical neonates contributes to neonatal mortality rates. The study was conceptualized to study clinical and nonclinical factors affecting mortality in surgical neonates so that timely intervention could result in improved survival of the neonates. Materials and Methods: The study was initiated after approval from the institutional ethics committee and included 120 surgical neonates over a period of 18 months after obtaining consent from the parents/caregivers. Predesigned pro forma was used to record the details of antenatal care received, place of birth, travel history, maternal education and gestational age, and clinical condition at the time of admission. Values of biochemical tests such as serum electrolytes, serum creatinine, and arterial blood gasses were recorded. The need of inotrope support, blood or blood product transfusion, and postoperative ventilator support and intensive care unit (ICU) care was recorded. The results of the two groups, i.e., survivals and mortality, were compared. Outcome was recorded as mortality at 30 days or earlier. Results: Irrespective of the surgical condition, the survival rate was significantly better in those babies who weighed more than 2.5 kg at the time of admission, had capillary refill time of <3 s, had serum ionized calcium levels more than 1 mmol/L, and did not require inotropes, blood or blood product transfusion, and postoperative ICU care and ventilator support. The place of birth, educational status of the mother, gestational age, and distance traveled for care had no statistically significant effect on survival. Conclusion: There is a statistically significant correlation between the survival of the babies who weighed more than 2.5 kg and are more physiologically preserved at the time of admission. Mortality rates can be decreased by timely interventions to reduce the need of inotropes, blood or blood products, and ICU care and ventilator support during their postoperative recovery. [ABSTRACT FROM AUTHOR]

We review the exciting potential (and challenges) of quantitative nailfold capillaroscopy, focusing on its role in systemic sclerosis. Quantifying abnormality, including automated analysis of nailfold images, overcomes the subjectivity of qualitative/descriptive image interpretation. First we consider the rationale for quantitative analysis, including the potential for precise discrimination between normal and abnormal capillaries and for reliable measurement of disease progression and treatment response. We discuss nailfold image acquisition and interpretation, and describe how early work on semi-quantitative and quantitative analysis paved the way for semi-automated and automated analysis. Measurement of red blood cell velocity is described briefly. Finally we give a personal view on 'next steps'. From a clinical perspective, increased uptake of nailfold capillaroscopy by general rheumatologists could be achieved via low-cost hand-held devices with cloud-based automated analysis. From a research perspective, automated analysis could facilitate large-scale prospective studies using capillaroscopic parameters as possible biomarkers of systemic sclerosis-spectrum disorders. [ABSTRACT FROM AUTHOR]

The pancreatic islet is a highly vascularized endocrine micro-organ. The unique architecture of rodent islets, a so-called core-mantle arrangement seen in two-dimensional images, led researchers to seek functional implications for islet hormone secretion. Three models of islet blood flow were previously proposed, all based on the assumption that islet microcirculation occurs in an enclosed structure. Recent electrophysiological and molecular biological studies using isolated islets also presumed unidirectional flow. Using intravital analysis of the islet microcirculation in mice, we found that islet capillaries were continuously integrated to those in the exocrine pancreas, which made the islet circulation rather open, not self-contained. Similarly in human islets, the capillary structure was integrated with pancreatic microvasculature in its entirety. Thus, islet microcirculation has no relation to islet cytoarchitecture, which explains its well-known variability throughout species. Furthermore, tracking fluorescent-labeled red blood cells at the endocrine-exocrine interface revealed bidirectional blood flow, with similar variability in blood flow speed in both the intra- and extra-islet vasculature. To date, the endocrine and exocrine pancreas have been studied separately by different fields of investigators. We propose that the open circulation model physically links both endocrine and exocrine parts of the pancreas as a single organ through the integrated vascular network. [ABSTRACT FROM AUTHOR]

Skeletal muscle is highly vascularized, with perfusion being tightly regulated to meet wide-ranging metabolic demands. For decades, the capillary supply has been explored mainly in terms of evaluating the capillary numbers and their function in the supply of oxygen and substrates and the removal of metabolic byproducts. This review will focus on recent discoveries concerning the role played by capillaries in facilitating other aspects of cell regulation and maintenance, in health and disease, as well as alterations during the aging process. [ABSTRACT FROM AUTHOR]

Maximum oxygen consumption ( V ˙ O 2 max ) is not only an indicator of endurance performance, but also a strong predictor of cardiovascular disease and mortality. This physiological parameter is known to decrease with aging. In turn, physical exercise might attenuate the rate of aging-related decline in V ˙ O 2 max , which in light of the global population aging is of major clinical relevance, especially at advanced ages. In this narrative review, we summarize the evidence available from masters athletes about the role of lifelong endurance exercise on aging-related V ˙ O 2 max decline, with examples of the highest V ˙ O 2 max values reported in the scientific literature for athletes across different ages (e.g., 35 ml·kg−1·min−1 in a centenarian cyclist). These data suggest that a linear decrease in V ˙ O 2 max might be possible if physical exercise loads are kept consistently high through the entire life span, with V ˙ O 2 max values remaining higher than those of the general population across all ages. We also summarize the main physiological changes that occur with inactive aging at different system levels—pulmonary and cardiovascular function, blood O2 carrying capacity, skeletal muscle capillary density and oxidative capacity—and negatively influence V ˙ O 2 max , and review how lifelong exercise can attenuate or even prevent most—but apparently not all (e.g., maximum heart rate decline)—of them. In summary, although aging seems to be invariably associated with a progressive decline in V ˙ O 2 max , maintaining high levels of physical exercise along the life span slows the multi-systemic deterioration that is commonly observed in inactive individuals, thereby attenuating age-related V ˙ O 2 max decline. [ABSTRACT FROM AUTHOR]

Introduction: High flow rates may develop in arteriovenous fistula (AVF), resulting in clinical syndromes of steal, aneurysmal fistula, or high-output cardiac failure. Various techniques with varying success have been advocated to treat this difficult problem. We present a hemodynamically validated novel banding technique. Methods: We designed a computational fluid dynamic (CFD) model of the native high-flow AVF and tested various juxta-anastomotic venous diameters to determine the effect on AVF blood flow and pressure. We translated this principle in our banding technique, wherein adjustable banding was performed in conjunction with ultrasound-guided brachial artery flow measurement to determine the optimal band diameter. Polyurethane patch was used to fashion the adjustable band. Patient demographics, AVF flow parameters pre- and postintervention, operative intervention, and ultrasound follow-up data were collected prospectively. Results: Our CFD testing demonstrated that the band diameter needed to achieve optimal distal blood pressure and preserve AVF flow depending on blood pressure, end capillary pressure, venous pressure, and vascular diameters. Five patients subsequently underwent dynamic banding of symptomatic highflow AVF. Mean brachial artery blood flow rates pre- and postbanding were 2964 mL/min (confidence interval [CI]: 1487-4440 mL/min) and 1099 mL/min (CI: 571.7-1627 mL/min), respectively (P = .01). All patients had symptomatic improvement, and at a mean follow-up of 1 year, this benefit was sustained with no AVF thrombosis or loss. Conclusion: Adjustable dynamic band using ultrasound-guided brachial artery flow shows promising results in producing accurate AVF blood flow reduction with sustained efficacy in the short term for patients with symptomatic high-flow AVF. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to provide an evaluation of the oxygen transport, exchange and storage capacity of elite breath-hold divers (EBHD) compared with non-divers (ND).Methods: Twenty-one healthy males' (11 EBHD; 10 ND) resting splenic volumes were assessed by ultrasound and venous blood drawn for full blood count analysis. Percutaneous skeletal muscle biopsies were obtained from the m. vastus lateralis to measure capillarisation, and fibre type-specific localisation and distribution of myoglobin and mitochondrial content using quantitative immunofluorescence microscopy.Results: Splenic volume was not different between groups. Reticulocytes, red blood cells and haemoglobin concentrations were higher (+ 24%, p < 0.05; + 9%, p < 0.05; + 3%, p < 0.05; respectively) and mean cell volume was lower (- 6.5%, p < 0.05) in the EBHD compared with ND. Haematocrit was not different between groups. Capillary density was greater (+ 19%; p < 0.05) in the EBHD. The diffusion distance (R95) was lower in type I versus type II fibres for both groups (EBHD, p < 0.01; ND, p < 0.001), with a lower R95 for type I fibres in the EBHD versus ND (- 13%, p < 0.05). Myoglobin content was higher in type I than type II fibres in EBHD (+ 27%; p < 0.01) and higher in the type I fibres of EBHD than ND (+ 27%; p < 0.05). No fibre type differences in myoglobin content were observed in ND. Mitochondrial content was higher in type I than type II fibres in EBHD (+ 35%; p < 0.05), with no fibre type differences in ND or between groups.Conclusions: In conclusion, EBDH demonstrate enhanced oxygen storage in both blood and skeletal muscle and a more efficient oxygen exchange capacity between blood and skeletal muscle versus ND. [ABSTRACT FROM AUTHOR]

Purpose: Obstructive sleep apnoea (OSA) is a highly prevalent sleep-related breathing disorder associated with hypertension, impaired peripheral vascular function and an increased risk of stroke. Evidence suggests that abnormalities of the cerebral microcirculation, such as capillary rarefication, may be present in these patients. We evaluated whether the presence of hypertension may affect the cerebral capillary architecture and function assessed by Intravoxel Incoherent Motion (IVIM) magnetic resonance imaging (MRI) in patients with continuous positive airway pressure (CPAP)-treated OSA. Methods: Forty-one patients (88% male, mean age 57 ± 10 years) with moderate-to-severe OSA were selected and divided into two groups (normotensive vs. hypertensive). All hypertensive OSA patients were adherent with their antihypertensive medication. Cerebral microvascular structure was assessed in grey (GM) and white matter (WM) using an echo-planar diffusion imaging sequence with 14 different b values. A step-wise IVIM analysis algorithm was applied to compute true diffusion (D), perfusion fraction (f) and pseudo-diffusion (D*) values. Group comparisons were performed with the Wilcoxon-Mann-Whitney-Test. Regression analysis was adjusted for age. Results: Diffusion- and perfusion-related indexes in middle-aged OSA normotensive patients were quantified in both tissue types (D [10−3 mm2/s]: GM = 0.83 ± 0.03; WM = 0.72 ± 0.03; f (%) GM = 0.09 ± 0.01; WM = 0.06 ± 0.01; D* [10−3 mm2/s]: GM = 7.72 ± 0.89; WM = 7.38 ± 0.98). In the examined tissue types, hypertension did not result in changes on the estimated MRI IVIM index values. Conclusion: Based on IVIM analysis, cerebral microvascular structure and function showed no difference between hypertensive and normotensive patients with moderate-to-severe OSA treated with CPAP. Treatment adherence with antihypertensive drug regime and, in turn, controlled hypertension seems not to affect microvascular structure and perfusion of the brain. Trial registration: ClinicalTrials.gov Identifier: NCT02493673 [ABSTRACT FROM AUTHOR]

In the conventional concept of translational research, investigations flow from the laboratory bench to the bedside. However, clinical research can also serve as the starting point for subsequent laboratory investigations that then lead back to the bedside. This article chronicles the evolution of a series of studies in which a detailed analysis of pharmacokinetics in hemodialysis patients revealed new physiological insight that, through a systems approach incorporating kinetic, physicochemical, physiologic, and clinical trial results, led to an elucidation of the pathophysiology of intradialytic skeletal muscle cramps. Based on this understanding, a therapeutic path forward is proposed. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is associated with microvascular dysfunction, but little is known about how capillary ultrastructure is affected by exercise training. To investigate the effect of two types of exercise training on skeletal muscle capillary ultrastructure and capillarization in individuals with type 2 diabetes, 21 individuals with type 2 diabetes were allocated (randomized controlled trial) to 11 weeks of aerobic exercise training consisting of either moderate‐intensity endurance training (END; n = 10) or low‐volume high‐intensity interval training (HIIT; n = 11). Skeletal muscle biopsies (m vastus lateralis) were obtained before and after the training intervention. At baseline, there was no difference in capillarization, capillary structure, and exercise hyperemia between the two groups. After the training intervention, capillary‐to‐fiber ratio increased by 8% ± 3% in the END group (P < 0.05) and was unchanged in the HIIT group with no difference between groups. Endothelium thickness increased (P < 0.05), basement membrane thickness decreased (P < 0.05), and the capillary lumen tended (P = 0.07) to increase in the END group, whereas these structural indicators were unchanged after HIIT. In contrast, skeletal muscle endothelial nitric oxide synthase (eNOS) increased after HIIT (P < 0.05), but not END, whereas there was no change in vascular endothelial growth factor (VEGF), superoxide dismutase (SOD)‐2, or NADPH oxidase after both training protocols. In contrast to END training, HIIT did not alter capillarization or capillary structure in individuals with type 2 diabetes. In conclusion, HIIT appears to be a less effective strategy to treat capillary rarefaction and reduce basement thickening in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Physical inactivity alters glucose homeostasis in skeletal muscle, potentially developing into overt metabolic disease. The present study sought to investigate the role of skeletal muscle capillarization in glucose tolerance and insulin sensitivity (IS) using a classic human model of physical inactivity. Thirteen healthy males (age = 23 ± 2 years) underwent 4 days of full-time supervised and diet-controlled bed rest. Oral glucose tolerance test, indices of IS (quantitative insulin sensitivity check index (QUICKI), Matsuda index), as well as skeletal muscle biopsies with measurement of fiber type distribution, fiber cross-sectional area (FCSA), capillary-to-fiber ratio (C/F ratio), and capillary density (CD) were assessed prior to and after bed rest. Body weight and composition were unaltered by bed rest. Fasting glucose/insulin ratio (G0/I0 ratio) (−25%, P = 0.016), QUICKI (−7%, P = 0.023), and Matsuda index (−24%, P = 0.003) diminished with bed rest. Skeletal muscle FCSA decreased (−737.4 ± 763.2 μm−2 (−12%), P = 0.005) while C/F ratio was preserved, resulting in augmented CD (+93.9 ± 91.5 capillaries·mm−2 (+37%), P = 0.003) with bed rest. No association was detected between changes in skeletal muscle variables and metabolic outcomes. Independently of bed rest-induced effects, a positive linear relationship was detected between C/F ratio and G0/I0 ratio (β = 17.09, P = 0.021). In conclusion, impaired glucose homeostasis with bed rest is not prevented nor associated with enhanced skeletal muscle capillarization in healthy individuals. [ABSTRACT FROM AUTHOR]

The effect of pore size on filtration performance of coalescing filters was investigated experimentally, using four oleophilic and three oleophobic glass-fiber filter materials. The filters were fabricated into sandwiches composed of a varying number of layers, each of the same filter materials. The results showed that both trend and extent of variation of the excess channel pressure drop with number of layers were dominated by the pore size. As the pore size decreased, the excess channel pressure drop exhibited the increasing, stable, and decreasing trends with increasing number of layers for oleophobic filters, respectively, while it kept growing with number of layers for oleophilic filters. The jump pressure drop controlled by liquid film was inversely proportional to the mean pore size, with an empirical fit equation established to allow quantitative analysis of relationship between film thickness and mean pore size for oleophilic filters. The pore size was a dominant factor in improving steady-state filtration efficiency, as a large-mean-pore-size filter was unable to efficiently separate sub-micrometer-sized droplets even with a high number of layers. Conversely, it was found that re-entrainment of micrometer-sized droplets was prone to occur in small-mean-pore-size oleophobic and large-mean-pore-size oleophilic filters, resulting in the pronounced reduction of steady-state filtration efficiency. Based on quality factors at steady state, a filter with large mean pore size was much superior in separation of micrometer-sized droplets, while a filter with moderate rather than smallest mean pore size, should be applied to separate sub-micrometer-sized droplets. [ABSTRACT FROM AUTHOR]

Abstract: Background: Age‐related sarcopenia is accelerated by physical inactivity. Low‐load resistance exercise (LLRE) counters inactivity‐induced muscle atrophy in older adults, but changes in muscle fibre morphology are unstudied. We aimed to determine the impact of LLRE during short‐term inactivity (step‐reduction) on muscle fibre size and capillarity as well as satellite cell (SC) content in older skeletal muscle. Methods: Fourteen older (~71 years) male adults underwent 14 days of step reduction (<1500 steps/day) while performing six sessions of LLRE (~30% maximal strength) with one leg (SR + EX) while the contralateral leg served as an untrained control (SR). Seven healthy ambulatory age‐matched male adults (~69 years) served as a comparator group (COM). Muscle biopsies were taken from the vastus lateralis after 14 days, and immunohistochemical analysis was performed to determine muscle fibre cross‐sectional area (CSA), myonuclear content, SC content (PAX7+ cells), and total (C:F) and fibre type‐specific (C:Fi) capillary‐to‐fibre ratios. Results: Type I and II fibre CSA was greater in SR + EX compared with SR. Whereas there were no differences across fibre types between SR + EX and CON, type II fibre CSA was significantly lower in SR compared with COM. Type II myonuclear domain was greater in SR + EX compared with COM and SR. Pax7+ cells associated with type I and II fibres were lower in SR compared with SR + EX. Type II PAX7+ cells were also lower in SR compared with COM with a similar trend for type I fibres. There were trends for a lower C:Fi in SR compared with SR + EX for both fibre types with no differences for each compared with COM. Conclusions: Minimal LLRE during a period of decreased physical activity is associated with greater muscle fibre CSA, SC content, and capillarization. These results support the use of LLRE as an effective countermeasure to inactivity‐induced alterations in muscle morphology with age. [ABSTRACT FROM AUTHOR]

Spreading depolarization is assumed to be the mechanism of migraine with aura, which is accompanied by an initial predominant hyperaemic response followed by persistent vasoconstriction. Cerebral blood flow responses are impaired in patients and in experimental animals after spreading depolarization. Understanding the regulation of cortical blood vessels during and after spreading depolarization could help patients with migraine attacks, but our knowledge of these vascular mechanisms is still incomplete. Recent findings show that control of cerebral blood flow does not only occur at the arteriole level but also at capillaries. Pericytes are vascular mural cells that can constrict or relax around capillaries, mediating local cerebral blood flow control. They participate in the constriction observed during brain ischaemia and might be involved the disruption of the microcirculation during spreading depolarization. To further understand the regulation of cerebral blood flow in spreading depolarization, we examined penetrating arterioles and capillaries with respect to vascular branching order, pericyte location and pericyte calcium responses during somatosensory stimulation and spreading depolarization. Mice expressing a red fluorescent indicator and intravenous injections of FITC-dextran were used to visualize pericytes and vessels, respectively, under two-photon microscopy. By engineering a genetically encoded calcium indicator we could record calcium changes in both pericytes around capillaries and vascular smooth muscle cells around arterioles. We show that somatosensory stimulation evoked a decrease in cytosolic calcium in pericytes located on dilating capillaries, up to the second order capillaries. Furthermore, we show that prolonged vasoconstriction following spreading depolarization is strongest in first order capillaries, with a persistent increase in pericyte calcium. We suggest that the persistence of the 'spreading cortical oligaemia' in migraine could be caused by this constriction of cortical capillaries. After spreading depolarization, somatosensory stimulation no longer evoked changes in capillary diameter and pericyte calcium. Thus, calcium changes in pericytes located on first order capillaries may be a key determinant in local blood flow control and a novel vascular mechanism in migraine. We suggest that prevention or treatment of capillary constriction in migraine with aura, which is an independent risk factor for stroke, may be clinically useful. [ABSTRACT FROM AUTHOR]

Abstract: Background: Absolute nailfold capillary number should be a putative biomarker in selected rheumatic diseases but could be time‐consuming and not highly repeatable. Objective: To validate an automated software for absolute nailfold capillary number and density evaluation, on NVC images in SSc. Methods: An automated software to count nailfold capillary number (AUTOCAPI) had been constructed, through an exploratory image set. Subsequently, application rules have been created to define the ROI in NVC images, through a training images set. The software reliability was assessed through calculation of the ICC between automatic and manual counting, by four independent observers, on the same NVC images. Results: The following ICC's were obtained per observer, for the patients with SSc (40 images), the healthy (20 images), and the PRP subgroups (20 images), respectively: 0.94, 0.81, and 0.62 (observer 1); 0.94, 0.91, and 0.67 (observer 2); 0.88, 0.56, and 0.64 (observer 3); and 0.88, 0.85, and 0.85 (observer 4). Conclusions: The validation of an automated software for measuring absolute nailfold capillary number and density in SSc was achieved. The integration into the pre‐existing imaging software should make the assessment of the capillary number in NVC easier, quicker, and standardized. [ABSTRACT FROM AUTHOR]

Abstract: Objective: CCA, outward remodeling of capillaries that anastomose 2 arteriolar trees with different parent feed arteries, may represent a therapeutic target for patients who lack collaterals. ACCs can reperfuse an ischemic tree, but their functional capacity is unknown. Therefore, we determined whether ACCs mature into resistance vessels that regulate blood flow following arterial occlusion. Methods: We ligated the lateral spinotrapezius feed artery in Balb/C mice, which induces CCA. At days 7 and 21 following occlusion, we measured vasodilation of ACCs using intravital microscopy and blood flow in the ischemic tree using LSF. We determined the presence of ACCs and neurovascular alignment with immunofluorescence. Results: At day 7, ACCs do not vasodilate following muscle contraction and have reduced responses to endothelial‐ and smooth muscle‐dependent agents. By day 21, ACCs exhibit normal vasodilation, accompanied by normalized increases in relative blood flow to the ischemic zone. Although functioning as resistance vessels by regulating blood flow, ACCs do not appear to be innervated. Conclusions: ACCs mature into resistance vessels that regulate blood flow to the downstream tissue. Therefore, induction of mature ACCs may be a target for reducing ischemia in patients who lack collateral networks. [ABSTRACT FROM AUTHOR]

Key points: Skeletal muscle stem cells (satellite cells) play a crucial role in repair and remodelling of muscle in response to exercise. Satellite cells are in close spatial proximity to muscle capillaries and therefore may be influenced by them. In this study, we describe the activation and expansion of the satellite cell pool in response to eccentric contraction‐induced muscle damage in individuals with significantly different levels of muscle capillarization. Individuals with greater capillarization and capacity for muscle perfusion demonstrated enhanced activation and/or expansion of the satellite cell pool allowing for an accelerated recovery of muscle function. These results provide insight into the critical relationship between muscle capillarization and satellite cells during skeletal muscle repair. Abstract: Factors that determine the skeletal muscle satellite cell (SC) response remain incompletely understood. It is known, however, that SC activation status is closely related to the anatomical relationship between SCs and muscle capillaries. We investigated the impact of muscle fibre capillarization on the expansion and activation status of SCs following a muscle‐damaging exercise protocol in healthy young men. Twenty‐nine young men (21 ± 0.5 years) performed 300 unilateral eccentric contractions (180 deg s−1) of the knee extensors. Percutaneous muscle biopsies from the vastus lateralis and blood samples from the antecubital vein were taken prior to (Pre) exercise and at 6, 24, 72 and 96 h of post‐exercise recovery. A comparison was made between subjects who had a relative low mixed muscle capillary‐to‐fibre perimeter exchange index (CFPE; Low group) and high mixed muscle CFPE index (High group) at baseline. Type I and type II muscle fibre size, myonuclear content, capillarization, and SC response were determined via immunohistochemistry. Overall, there was a significant correlation (r = 0.39; P < 0.05) between the expansion of SC content (change in total Pax7+ cells/100 myofibres) 24 h following eccentric exercise and mixed muscle CFPE index. There was a greater increase in activated SCs (MyoD+/Pax7+ cells) in the High as compared to the Low CFPE group 72 h following eccentric exercise (P < 0.05). The current study provides further evidence that muscle fibre capillarization may play an important role in the activation and expansion of the SC pool during the process of skeletal muscle repair. [ABSTRACT FROM AUTHOR]

Aims: NADPH oxidase-4 (Nox4) is an important reactive oxygen species (ROS) source that is upregulated in the haemodynamically overloaded heart. Our previous studies using global Nox4 knockout (Nox4KO) mice demonstrated a protective role of Nox4 during chronic abdominal aortic banding, involving a paracrine enhancement of myocardial capillary density. However, other authors who studied cardiac-specific Nox4KO mice reported detrimental effects of Nox4 in response to transverse aortic constriction (TAC). It has been speculated that these divergent results are due to cell-specific actions of Nox4 (i.e. cardiomyocyte Nox4 detrimental but endothelial Nox4 beneficial) and/or differences in the model of pressure overload (i.e. abdominal banding vs. TAC). This study aimed to (i) investigate whether the effects of Nox4 on pressure overload-induced cardiac remodelling vary according to the pressure overload model and (ii) compare the roles of cardiomyocyte vs. endothelial cell Nox4. Methods And Results: Global Nox4KO mice subjected to TAC developed worse cardiac remodelling and contractile dysfunction than wild-type littermates, consistent with our previous results with abdominal aortic banding. Next, we generated inducible cardiomyocyte-specific Nox4 KO mice (Cardio-Nox4KO) and endothelial-specific Nox4 KO mice (Endo-Nox4KO) and studied their responses to pressure overload. Both Cardio-Nox4KO and Endo-Nox4KO developed worse pressure overload-induced cardiac remodelling and dysfunction than wild-type littermates, associated with significant decrease in protein levels of HIF1α and VEGF and impairment of myocardial capillarization. Conclusions: Cardiomyocyte as well as endothelial cell Nox4 contributes to protection against chronic hemodynamic overload-induced cardiac remodelling, at least in part through common effects on myocardial capillary density. [ABSTRACT FROM AUTHOR]

This study extends our previous studies on the effects of the IFT on the seepage characteristics in hydrate-bearing porous media using pore network model with X-ray computed tomography. The results indicate that the relative permeability to both methane gas and water decreases as IFT increases. And the influence of the IFT on the two-phase relative permeability increases along with the particle size of the porous media. Moreover, the variation in absolute permeability is always positively related to average pore/throat radii in all type of hydrate-bearing porous media. In addition, the capillary pressure decreases along with IFT. [ABSTRACT FROM AUTHOR]

Background and Objectives: The aim of this study was to investigate (1) the hydrocolloid properties of grass jelly on reducing glycaemic response, (2) the impact of phenolic compounds in Mesona chinensis L. on glycaemic response.Methods and Study Design: A total of 15 healthy Chinese men were recruited to this study. On each visit, subjects consumed one of the following three treatments, i.e. glucose solution (T1), grass jelly (Mesona chinensis L.) solution with glucose (T2) or grass jelly gel with glucose (T3). Capillary blood glucose and venous plasma insulin were analysed over a period of 180 min.Results: The incremental area under the curve for capillary glucose and venous plasma insulin for glucose group, grass jelly solution group and grass jelly gel was found to be statistically not significant (p>0.05). In a previous study the co-ingestion of grass jelly with complex carbohydrate was found to reduce glycaemic response. The key difference between the two studies was the use of monosaccharide glucose in the present study, compared to complex carbohydrates in the other. The present study suggests that the glycaemic lowering effect of grass jelly may be dependent on the inhibition of carbohydrase enzymes.Conclusions: The co-ingestion of Mesona chinensis L. appears to reduce glycaemic response of only complex carbohydrates through the inhibition of carbohydrase. This conclusion was arrived at by the lack of any effect of Mesona chinensis L. on the monosaccharide glucose. [ABSTRACT FROM AUTHOR]

Spontaneous endothelialization of synthetic vascular grafts may occur via three independent or concurrent modalities: transanastomotic (TA) outgrowth, transmural (TM) ingrowth or fallout (FO) from the blood. The limited TA and FO endothelialization, which occurs in humans, results in poor long-term patency in the small diameter position, where TM ingrowth may offer a clinically relevant alternative. To achieve sequential analysis of each mode of healing, loop grafts comprising anastomotically isolated angiopermissive polyurethane control grafts were abluminally sealed using either ePTFE wraps or solid polyurethane skins and implanted in the rat infrarenal aortic loop model for twelve weeks. Positive control grafts showed improved endothelialization and patency compared to the abluminally isolated mid-grafts. Furthermore, the mid-graft healing was accelerated with surface heparin and heparin-growth factor (VEGF, PDGF) modification in a three-week sub-study. We are thus able to distinguish between the three vascular graft endothelialization modes, and conclude that fallout plays a secondary role to TM healing. The increased endothelialisation for growth factor presenting grafts indicates the promise of this simple approach but further optimization is required . Statement of Significance In addition to the full elucidation of, and differentiation between, the three healing/endothelialisation modes of vascular grafts, the significance of the work relates to the near-complete lack of endothelialisation of small diameter vascular grafts in humans (1–2 cm transanastomotic outgrowth on a graft that may be 60 cm long) even after decades of implantation. The concomitant retained midgraft thrombogenicity leads, together with anastomotic hyperplastic responses, to poor long-term outcomes. The large impact of successful translation of the current research to the achievement of full endothelialisation of long peripheral grafts in humans via transmural ingrowth (half a millimetre distance; thickness of the graft wall), is evident, and supported by the large improvements in clinical patencies achievable in by pre-seeding of ePTFE grafts with confluent endothelia. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies suggest that exercise and heat stress improve cutaneous endothelial function, caused by increases in shear stress. However, as vasodilatation in the skin is primarily a thermogenic phenomenon, we investigated if shear stress alone without increases in skin temperature that occur with exercise and heat stress increases endothelial function. We examined the hypothesis that repeated bouts of brief occlusion would improve cutaneous endothelial function via shear stress-dependent mechanisms.Methods: Eleven males underwent a shear stress intervention (forearm occlusion 5 s rest 10 s) for 30 min, five times·week-1 for 6 weeks on one arm, the other was an untreated control. Skin blood flow was measured using laser-Doppler flowmetry, and endothelial function was assessed with and without NOS-inhibition with L-NAME in response to three levels of local heating (39, 42, and 44 °C), ACh administration, and reactive hyperaemia. Data are cutaneous vascular conductance (CVC, laser-Doppler/blood pressure).Results: There were no changes in the control arm (all d ≤ 0.2, p > 0.05). In the experimental arm, CVC to 39 °C was increased after 3 and 6 weeks (d = 0.6; p ≤ 0.01). Nitric oxide contribution was increased after 6 weeks compared to baseline (d = 0.85, p < 0.001). Following skin heating to 42 °C and 44 °C, CVC was not different at weeks 3 or 6 (d ≤ 0.8, p > 0.05). For both 42 and 44 °C, nitric oxide contribution was increased after weeks 3 and 6 (d ≥ 0.4, p < 0.03). Peak and area-under-the-curve responses to ACh increased following 6 weeks (p < 0.001).Conclusions: Episodic increases in shear stress, without changes in skin or core temperature, elicit an increase in cutaneous microvascular reactivity and endothelial function. [ABSTRACT FROM AUTHOR]

Rammed earth constructions exhibit strength and deformation properties that evolve as a function of the relative humidity of the air in contact with the walls. This effect must be considered in the structural design of the construction. This work studies, through finite element simulation, the impact of the hygroscopic transfers through the wall on the structural response of a classical two-storey rammed earth building. The coupling between the mechanical and the hygroscopic behaviour is considered by the concept of effective stress for unsaturated soils, in order to reproduce the effect of suction on the strength, the stiffness and the volumetric variations of the rammed earth. The simulations show classical deformation of the structure due to distributed load on the floors while the hygroscopic changes in the rammed earth (essentially drying) induce additional displacements of the walls that remain in a very acceptable range. Finally, an extreme case is envisaged in which the loads on the floors are increased excessively in order to study the plastic response of the wall. [ABSTRACT FROM AUTHOR]

We examined the circulatory mechanisms underlying adaptive increases in thermogenic capacity in deer mice (Peromyscus maniculatus) native to the cold hypoxic environment at high altitudes. Deer mice from high- and low-altitude populations were born and raised in captivity to adulthood, and then acclimated to normoxia or hypobaric hypoxia (simulating hypoxia at ~4300m). Thermogenic capacity [maximal O2 consumption (VO2,max), during cold exposure] was measured in hypoxia, along with arterial O2 saturation (SaO2) and heart rate (fH). Hypoxia acclimation increased VO2,max by a greater magnitude in highlanders than in lowlanders. Highlanders also had higher SaO2 and extracted more O2 from the blood per heartbeat (O2 pulse=VO2,max/fH). Hypoxia acclimation increased fH, O2 pulse and capillary density in the left ventricle of the heart. Our results suggest that adaptive increases in thermogenic capacity involve integrated functional changes across the O2 cascade that augment O2 circulation and extraction from the blood. [ABSTRACT FROM AUTHOR]

Aim Most guidelines provide people with Type 1 diabetes with pre- and post-meal capillary blood glucose ( CBG) targets to achieve optimal glycaemic control. We evaluated the proportion of daily CBG readings between 4 and 10 mmol/l in people achieving different HbA1c levels. Method We analysed CBG data from routine pump/meter downloads from 201 adults treated with continuous subcutaneous insulin infusion ( CSII) at a single hospital clinic. Exclusion criteria were CSII < 6 months, < 3 CBG/day, pregnancy, haemoglobinopathy and continuous sensor use. People were categorized into three groups based on HbA1c: < 58 mmol/mol, < 7.5% ( n = 58); 58-74 mmol/mol, 7.5-8.9% ( n = 107); and ≥ 75 mmol/mol, ≥ 9.0% ( n = 36). Results Participants had a mean age of 43 ± 13 years and mean HBA1c of 64 mmol/mol (8.0 ± 1.1%). 47% of people started CSII for raised HbA1c, 25% due to hypoglycaemia and the rest during pregnancy. Downloads contained a mean of 22 ± 6.8 days of data per participant. CBG frequency was similar between the three groups (5.6 ± 2.0, 5.6 ± 1.9 and 5.4 ± 1.2 CBG/day; P = 0.468). The proportion of CBG readings between 4 and 10 mmol/l (72-180 mg/dl) was 57.3 ± 25.4%, 50.6 ± 11.1% and 39.9 ± 16.5% ( P < 0.0001); < 4 mmol was 13.8%, 8.8% and 4.4% ( P < 0.0001) and > 10 mmol/l was 28.9 ± 16.5%, 40.6 ± 12.1% and 55.6 ± 17.9% ( P < 0.0001) in the three groups respectively. Conclusions Participants achieving HBA1c < 58 mmol/mol (< 7.5%) had ~ 60% of CBG readings in range (4-10 mmol/l), with up to 30% of readings > 10 mmol/l. This target of achieving 60% or more readings within target, and being permissive with up to 30% readings > 10 mmol/l may be a novel target for people with diabetes, and may reduce anxiety associated with readings out of range. [ABSTRACT FROM AUTHOR]

Compositional reservoir simulation plays a vital role in the development of conventional and unconventional reservoirs. Two major building blocks of compositional simulation are phasebehavior and fluid-transport computations. The oil and gas reserves and flow of reservoir fluids are strongly dependent on phase behavior. In conventional reservoirs, capillary pressure is relatively small and is typically ignored in phase-behavior calculations. The approach is accepted as the norm to perform phaseequilibria calculation to estimate the oil and gas in place and fluid properties. However, large capillary pressure values are encountered in tight formations, such as shales, and therefore, its effects should not be ignored in phase-equilibria calculations. Many parameters and uncertainties contribute to the accuracy of the estimation and simulation results. In this research, the focus is on the effect of capillary pressure, and neglecting the effects of capillary pressure on phase behavior can lead to an inaccurate estimation of original oil in place (OOIP) and original gas in place (OGIP) as well as recovery performance because of the inherent assumption of equal phase pressures in the phase-equilibria calculation. Understanding of the effect of capillary pressure on phase behavior in tight reservoirs is by no means complete, especially by use of compositional simulation for hydraulically fractured reservoirs. In this paper, we develop a new compositional reservoir simulator capable of modeling discrete fractures and incorporating the effect of capillary pressure on phase behavior. Large-scale natural and hydraulic fractures in tight rocks and shales are modeled with a technique called the embedded-discrete-fracture model (EDFM), where fractures are modeled explicitly without use of local-grid refinement (LGR) or an unstructured grid. Flow of hydrocarbons occurs simultaneously within similar and different porosity types. Capillary pressure is considered in both flow and flash calculations, where simulations also include variable pore size as a function of gas saturation to accurately reflect temporal changes in each gridblock during the simulation. We examine the effect of capillary pressure on the OOIP and cumulative oil production for different initial reservoir pressures (above and below the bubblepoint pressure) on Bakken and Eagle Ford fluids. The importance of capillary pressure on both flow and flash calculations from hydraulically fractured horizontal wells during primary depletion in fractured tight reservoirs by use of two fluid compositions is demonstrated. Phase-behavior calculations show that bubblepoint pressure is suppressed, allowing the production to remain in the single-phase region for a longer period of time and also altering phase compositions and fluid properties, such as density and viscosity of equilibrium liquid and vapor. The results show that bubblepoint suppression is larger in the Eagle Ford shale than for Bakken. On the basis of the reservoir fluid and model used for the Bakken and Eagle Ford formations, when capillary pressure is included in the flash, we found an increase in OOIP up to 4.1% for the Bakken crude corresponding to an initial reservoir pressure of 2,000 psia and 46.33% for the Eagle Ford crude corresponding to an initial pressure of 900 psia. Depending on the initial reservoir pressure, cumulative primary oil production after 1 year increases because of the capillary pressure by approximately 9.0 to 38.2% for an initial reservoir-pressure range from 2,000 to 3,500 psia for Bakken oil and 7.2 to 154% for an initial reservoir-pressure range from 1,500 to 3,500 psia for Eagle Ford oil. The recovery increase caused by capillary pressure becomes more significant when reservoir pressure is far less than bubblepoint pressure. The simulation results with hydraulically fractured wells give similar recovery differences. For the two different reservoir settings in this study, at initial reservoir pressure of 5,500 psia, cumulative oil production after 1 year is 3.5 to 5.2% greater when capillary pressure is considered in phase-behavior calculations for Bakken. As initial reservoir pressure is lowered to 2,500 psia, the increase caused by capillary pressure is up to 28.1% for Bakken oil for the case studied. Similarly, at initial reservoir pressure of 2,000 psia, the increase caused by capillary pressure is 21.8% for Eagle Ford oil. [ABSTRACT FROM AUTHOR]

Roughton and Forster (RF) proposed to split the lung diffusing capacity into two contributions describing first, diffusion to red blood cells (RBC), and second, capture by diffusion from the RBC surface and reaction with haemoglobin. Solving the diffusion-reaction equations for simplified capillary-RBC structures, we investigate the RF interpretation. This reveals first that the conventional extrapolation to zero pressure of 1/DLCO on PO 2 is not a correct measure of the diffusive component. Consequently the capillary volumes deduced from this extrapolation are erroneous. Secondly, capture mechanisms are different for CO and NO: while DLCO characterizes “volume absorption” in the RBC and is correlated with hematocrit, DLNO quantifies “surface absorption” and provide information about the morphology of the space between the alveolar surface and the RBC surfaces. In conclusion, the RF approach may lead to erroneous physiological interpretations of DLCO; nevertheless, the measurement of DLCO and DLNO bring different types of information that give the potential for a better understanding of respiratory diseases. [ABSTRACT FROM AUTHOR]

A new and rather accurate correlation for prediction of effective diffusion coefficient is proposed for the biological tissue in the brain. Blood flow in brain capillaries and mass diffusion process in the tissues as a porous media, surrounding the capillaries, are simulated by using the random nature of tissue structure and the lattice Boltzmann method. The present correlation which is obtained from the lattice Boltzmann method and is taken into account the effects of the pore or cell structure is validated by comparing it with that of theoretical, statistical and experimental data. A very good coincidence between experimental data and present results have been found. So, the results show that the new model for the effective diffusion coefficient is a good choice for normal and damaged brain tissue and it produces more accurate results than existing models. [ABSTRACT FROM AUTHOR]

Purpose: Capillary transit time heterogeneity, measured as CTH, may set the upper limit for extraction of substances in brain tissue, e.g., oxygen. The purpose of this study was to investigate the feasibility of dynamic contrast-enhanced T1 weighted MRI (DCE-MRI) at 3 Tesla (T), in estimating CTH based on a gamma-variate model of the capillary transit time distribution. In addition, we wanted to investigate if a subtle increase of the blood-brain barrier permeability can be incorporated into the model, still allowing estimation of CTH.Materials and Methods: Twenty-three healthy subjects were scanned at 3.0T MRI system applying DCE-MRI and using a gamma-variate model to estimate CTH as well as cerebral blood flow (CBF), cerebral blood volume (CBV), and permeability of the blood-brain barrier, measured as the influx constant Ki . For proof of principle we also investigated three patients with recent thromboembolic events and a patient with a high grade brain tumor.Results: In the healthy subjects, we found a narrow symmetric delta-like capillary transit time distribution in basal ganglia gray matter with median CTH of 0.93 s and interquartile range of 1.33 s. The corresponding residue impulse response function was compatible with the adiabatic tissue homogeneity model. In two patients with complete occlusion of the internal carotid artery and in the patient with a brain tumor CTH was increased with values up to 6 s in the affected brain tissue, with an exponential like residue impulse response function.Conclusion: Our results open the possibility of characterizing brain perfusion by the capillary transit time distribution using DCE-MRI, theoretically a determinant of efficient blood to brain transport of important substances.Level Of Evidence: 2 J. MAGN. RESON. IMAGING 2017;45:1809-1820. [ABSTRACT FROM AUTHOR]

Background: Capillary refill time (CRT) is a clinical test used to evaluate the circulatory status of patients; various methods are available to assess CRT. Conventional clinical research often demands large numbers of patients, making it costly, labor-intensive, and time-consuming. We studied the interobserver agreement on CRT in a nationwide study by using a novel method of research called flash mob research (FMR).Methods: Physicians in the Netherlands were recruited by using word-of-mouth referrals, conventional media, and social media to participate in a nationwide, single-day, "nine-to-five," multicenter, cross-sectional, observational study to evaluate CRT. Patients aged ≥ 18 years presenting to the ED or who were hospitalized were eligible for inclusion. CRT was measured independently (by two investigators) at the patient's sternum and distal phalanx after application of pressure for 5 s (5s) and 15 s (15s).Results: On October 29, 2014, a total of 458 investigators in 38 Dutch hospitals enrolled 1,734 patients. The mean CRT measured at the distal phalanx were 2.3 s (5s, SD 1.1) and 2.4 s (15s, SD 1.3). The mean CRT measured at the sternum was 2.6 s (5s, SD 1.1) and 2.7 s (15s, SD 1.1). Interobserver agreement was higher for the distal phalanx (κ value, 0.40) than for the sternum (κ value, 0.30).Conclusions: Interobserver agreement on CRT is, at best, moderate. CRT measured at the distal phalanx yielded higher interobserver agreement compared with sternal CRT measurements. FMR proved a valuable instrument to investigate a relatively simple clinical question in an inexpensive, quick, and reliable manner. [ABSTRACT FROM AUTHOR]

The effects of dihydroquercetin (50 mg/kg intragastrically daily for 6 weeks) on the density of capillary network (mean number of capillaries per mm), mean capillary diameter, structure of capillary network, capillary diameter distribution (<3, 3-5, 5-7, and 7-9 μ), and local cerebral blood flow (by laser Doppler) in the visual cortex were studied in SHR rats during the development of arterial hypertension (from the 6th to the 12th week of life). Normally, the systolic and diastolic BP progressively increased in SHR rats during this period. Dihydroquercetin did not affect the development of arterial hypertension. At the same time, the drug significantly increased the mean diameter of capillaries (by 11%), capillary network density (by 23%), and in the percentage of capillaries with a diameter of 3-9 μ (passable for erythrocytes; by 42%). Positive effects of dihydroquercetin on the structure of microcirculatory bed improved microcirculation: local cerebral blood flow in the visual cortex of SHR rats was significantly higher (by 36%) than in rats receiving no flavonoid and close to the value in Wistar-Kyoto rats. Dihydroquercetin improved microvascularization and microcirculation in the cerebral cortex of SHR rats during the formation of arterial hypertension. [ABSTRACT FROM AUTHOR]