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The Clinical Hemorheology & Microcirculation journal has established the A.L. Copley Best Paper Prize to recognize the best article published each year. The prize is named after Alfred Lewin Copley, the journal's founding editor. The winning paper for 2022 is titled "COVID-19 hemodynamic and thrombotic effect on the eye microcirculation after hospitalization: A quantitative case-control study" by Aristotle Koutsiaris and colleagues. The study investigates the impact of COVID-19 on the eye microcirculation of patients who received thromboprophylaxis after hospital discharge. The findings suggest that COVID-19 significantly reduces blood velocity and increases microthrombosis in the eye, potentially contributing to long COVID and indicating the presence of an unknown coagulation factor. [Extracted from the article]

Leukocyte activation, endothelial adhesion and functional capillary density were assessed by intravital microscopy of the bladder microcirculation following a single intravesical LPS administration with or without intravesical DIBI treatment. G. Hagn and colleagues received the B A.L. Copley Best Paper Prize b for their study about " B Anti-inflammatory iron chelator, DIBI, reduces leukocyte-endothelial adhesion and clinical symptoms of LPS-induced interstitial cystitis in mice b ". Four groups of female BALB/c mice were randomized into control group, IC group without therapy, IC group with DIBI therapy and control group with DIBI therapy. [Extracted from the article]

Whole blood and plasma viscosity were measured of 90 patients with chronic cerebrovascular disease (CVD) and 56 healthy individuals by Couette rotational viscometer Contraves Low Shear 30 at a steady flow. Plasma viscosity was measured with capillary viscometer of Ubbelohde type. Two subgroups of patients were investigated: 23 patients with transient ischemic attacks (TIAs) and 67 patients with chronic cerebral infarctions (CCI). They were compared with two control groups: 56 healthy individuals without risk factors for stroke and 37 randomly selected subjects with risk factors for stroke. It is established significant elevation of plasma viscosity in the patients with cerebral ischemia. The elevation of blood viscosity was most pronounced at shear rate of 94.5 s[sup -1]. This comparison is confirmed by the criterion, using blood rigidity number h defined by the formula of Whittington and Harkness. Conclusion is drawn from our study that chronic ischemic cerebrovascular disorders are characterized with chronic hyperviscosity. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the behaviour of circulating ET-1 in patients with carotid atherosclerosis, before and after carotid thromboendarterectomy (TEA), to test the hypothesis that plasma ET-1 decreases after removal of atherosclerotic lesion. Plasma immunoreactive ET-1 levels were determined in 17 patients with symptomatic and/or hemodynamically significant carotid atherosclerosis on the day before TEA, 48 h and 72 h after surgery and, in 11 of them, also after 8 h and 24 h. Compared to controls, ET-1 levels were significantly higher both before and after TEA; after carotid revascularisation (8 h) ET-1 increased; then, from the 24th h, ET-1 gradually decreased and at the 48th h and 72th h the decrease was significant in front of basal values. The increase of plasma ET-1 in the acute postoperative phase may reflect the degree of surgical stress and manipulation in diseased blood vessels; the following decrease may indicate the improvement of vascular dysfunction in the involved carotid site; the persistence of high ET-1 levels 72 h after surgery could suggest the presence of residual ischemia in the involved district and/or the involvement of other sites in ET-1 production. [ABSTRACT FROM AUTHOR]

Hypertension is the most significant cardiovascular risk factor to emerge in developing countries. 64 hypertensives (40 old hypertensives and 18 newly diagnosed hypertensives) and 40 age and sex matched normotensives controls were studied. Plasma fibrinogen concentration (PFC), euglobulin lysis time (ELT) and relative plasma viscosity (RPV) and relative whole blood viscosity (RWBV) were estimated. The PFC, RPV, RWBV and ELT were significantly higher in new and old hypertensives (P < 0.005), respectively, compared with controls, while the RPV was significantly higher (P < 0.005) in new hypertensives than old hypertensives. The significantly higher PFC, RPV and ELT in new hypertensives correspond to higher BP in the new hypertensives than old hypertensives. There were consistence significance levels in PFC, RPV and ELT in both female hypertensives and controls (P < 0.005), respectively, with higher BP in male than female. Though there were no significant mean differences between the hypertensive patients in the first two years of the disease, there were cumulative consistent increase in fibrinogen levels and euglobulin lysis time from two years; while RPV shows inconsistence variation until the 5th year. We conclude that a defective rheology and fibrin-clearing mechanism may contribute to aetiology of vascular complications in hypertensive patients especially in the long term. [ABSTRACT FROM AUTHOR]

Red blood cell (RBC) intercellular interactions, i.e., self-aggregation and adherence to endothelial cells (EC), play important roles in microcirculation. These RBC flow properties are determined by cell membrane components, which are prone to damaging reactive oxygen species (ROS) produced in oxidative stress (OS) states. Alterations in RBC aggregability and adherence have been linked to the pathophysiology in numerous diseases associated with OS. We investigated RBC intercellular interactions in four OS states — thalassemia, treatment of RBC with phenyl-hydrazine or H[sub 2]O[sub 2], and photodynamic virus inactivation of blood units. All these OS states increased RBC adherence to EC, but only part of them elevated their aggregability, while others abolished it. It is proposed that (1) different OS states might induce disparate effects on RBC intercellular interactions; (2) RBC aggregability and adherence to EC, although both intercellular interactions, are controlled by different cell surface factors. [ABSTRACT FROM AUTHOR]

Blood microrheology depends on the constituents of blood plasma, the interaction between blood cells resulting in red blood cell (RBC) and platelets aggregation, and adhesion of RBC, platelets and leukocytes to vascular endothelium. The main plasma protein molecule –actuator of RBC aggregation is fibrinogen. In this paper the effect of interaction between the endothelium and RBC at different fibrinogen concentrations on the RBC microrheological properties was investigated in vitro. Laser tweezers were used to measure the RBC-endothelium interaction forces. It was shown for the first time that the interaction forces between RBC and endothelium are comparable with the RBC aggregation forces, they increase with fibrinogen concentration and reach the saturation level of about 4 pN at the concentration of 4 mg/ml. These results are important for better understanding the mechanisms of RBC and endothelium interaction and developing the novel therapeutic protocols of the microrheology correction in different pathologies. [ABSTRACT FROM AUTHOR]

This review spans a wide arc from the first observations of the early anatomists to the present day. William Harvey was the first to describe the heart as the centre of the large and small circulatory system. He thus replaced the previously valid system of Galenos, It was Marcello Malpighi who first described that the capillary system connects the arteries with the veins. In 1688 Antoni van Leeuwenhoek (1632–1686) confirmed these results with a paper on capillary perfusion in the caudal fin of the glass eel. It was then Hermann Boerhave (1668–1738, Leiden) who was the first to carry out microcirculation tests on patients. He studied the microcirculation in the human bulbar conjunctiva. Even today, microcirculation studies in the conjunctiva bulbi of patients are carried out today. Until 1831, it was never quite clear whether the observations reported belonged mainly to the field of microcirculation, which had not yet been defined. This was done in Great Britain by Marshall Hall (1790–1857). Technical Improvements allowed increasingly sophisticated studies of the morphological structure of the terminal vasculature. According to Gustav Ricker (1870–1948, Vienna), the terminal vasculature comprises the functional unit of the smallest arteries, arterioles, capillaries and venules. In 1921 it was still thought that the blood circulation was the sole response to the pumping action of the heart. Even the classic work by Bayliss on the myogenic hypothesis (later referred to as "blood flow autoregulation") initially received little attention. More strikingly, even the findings of August Krogh, for which he received the Nobel Prize in Medicine in 1920 (for his discovery of the mechanisms of capillary motor regulation), were ignored. During an outstanding autoregulation symposium held in 1963 a broad consensus was reached on active and passive mechanisms, which is more or less valid till today. The mechanisms of regulation of capillary blood flow are now largely understood, although not completely resolved. The development of video systems with recording capability and automated off-line recording of capillary erythrocyte velocities allowed the application of morphological and dynamic studies of cutaneous capillaries in humans. These reopened the field of physiological or pathophysiological questions again for many groups worldwide. Since 1955, many publications on "microcirculation (5423)" and "capillary microscopy (2195)" have been listed in pubmed. [ABSTRACT FROM AUTHOR]

Ultrasound is the most used interdisciplinary non-ionizing imaging technique in clinical pathologies of the testis. The testis may be affected by a plethora of different disorders such as vasculopathies, trauma, infections and manifestations of primary and secondary malignant masses. Conventional ultrasound represents the basic imaging modality of choice to assess scrotal disorders. Contrast-enhanced ultrasound (CEUS) can provide further information to distinguish between benign and malignant testicular mass lesions. The recent introduction of Super Resolution CEUS Micro-Vascular Imaging (MVI SR) and Time of Arrival (TOA SR) parametric mapping compliments the information provided by conventional CEUS, since these two new post-processing techniques improve the visualization of microvascular structures with slow blood flow and provide high-resolution images of the peak contrast enhancement and temporal perfusion patterns. This paper gives a comprehensive overview of differential diagnoses of the testicular disorder and their corresponding sono-morphologic correlates based on representative cases of the Interdisciplinary Ultrasound Center of the University Hospital Munich. [ABSTRACT FROM AUTHOR]

The greater the viscosity of the blood, the more difficult its flow becomes, leading to an increased incidence of diseases caused by blood circulation disorders. These diseases are commonly associated with the cardiovascular and cerebrovascular systems. High blood viscosity is a primary cause of circulatory system diseases. Studies have shown that accurately measuring blood viscosity and applying this data in clinical trials can help prevent circulatory system diseases. Viscosity data can vary depending on the measurement methods used, even when these methods are based on hydrodynamic principles. Despite using approved blood viscometers, the results often differ depending on the type of viscometer used, potentially causing confusion within the medical field. Informing the medical community about these differences and the level of error associated with each measurement method can help reduce this confusion. To our knowledge, the degree of difference in viscosity measurement results due to different measurement methods and the reasons for these differences have not yet been thoroughly explored. In this study, we selected three blood viscosity measurement methods registered with the Ministry of Food and Drug Safety of Korea to analyze the same canine blood. The viscosity measurements were carried out using each device and compared. The parallel plate and scanning capillary methods yielded similar viscosity values, while the cone plate method showed lower viscosity values. The viscosity of blood, as measured by the three viscometers, differed, indicating that more experimental data must be accumulated to evaluate the cause of these differences. In this paper, we identified several causes of inconsistency and suggested measures to avoid this confusion. However, confirming that the test results show systematic differences is expected to assist clinicians who diagnose and prescribe treatments based on blood viscosity results. The findings of this comparative study are anticipated to serve as a starting point for establishing guidelines or standards for blood viscosity measurement methods. [ABSTRACT FROM AUTHOR]

The words "Translational" and "Medicine" have been recently coupled to indicate a combination of disciplines, resources, expertise, and techniques aimed at enhancing prevention, diagnosis, and therapies. As stated in 2015 by the European Society for Translational Medicine, translational medicine is "an interdisciplinary branch of the biomedical field supported by three main pillars: benchside, bedside and community". By definition, Translational Medicine is a highly interdisciplinary field, which gathers several specialties aimed at improving the global healthcare system. With regard to the assessment of the microcirculatory function, it is worthwhile to mention the growing interest from both basic research and clinical practice. Microcirculation is where the exchange of substances between blood and tissues takes place. Thus, it plays a key role in the pathophysiology of many diseases. Nonetheless, a gap does exist between the theoretical analysis of the microcirculatory function and its clinical exploitation. This gap can be due to the weak dissemination of analytical methods and theoretical results within the clinical community, which also delays the establishment of specific operative guidelines. This paper aims at encouraging, and possibly accelerating, the translation of basic research outcomes on microcirculatory function assessment into clinical applications. [ABSTRACT FROM AUTHOR]

Some open access journals are believed to have devaluated the highly respected image of the scientific journal. This has been, it is claimed, verified. Yet the project we believe failed and we show why we think that it failed. The study itself was badly conducted and the report, which Science published, was itself a perfect example of 'bad science'. If the article that was published in Science were to be taken as one of the 'test' articles and Science as a victim journal (a perfect control though), the study would show the opposite of what author concluded in his paper: 100% of the controls (normal non-open access journals, in the present study this was Science) accepted the 'bait' paper for publication, while in the experimental group only about 60% (open access journals) accepted the bait paper for publication. The conclusion is that, with respect to non-open access and open access, the probability of accepting pseudoscience is well in favor of this being done by a non-open access journal. Since this interpretation is based on some facts that were not included in the project itself, the only warranted result of this study would be that nothing could be concluded from it. It is concluded that the method that Bohannon used was heavily flawed and in addition immoral; that the report that was published by Science was inconclusive and that the act of publishing such report cannot be morally justified either. Various methods to improve the quality of published papers exist but scientific fraud with 'good intentions' as a method to promote scientific publishing should be avoided. [ABSTRACT FROM AUTHOR]

Presents the guidelines for authors to follow when submitting research papers to the 'Clinical Hemorheology and Microcirculation' journal.

According to Wells classification, it is possible to distinguish the primary hyperviscosity syndromes in polycythemic, sclerocythemic and sieric and/or plasmatic. In polycythemia vera, multiple myeloma, Waldenström's macroglobulinemia, and monoclonal gammopathy of undetermined significance, we have observed an unexpected behaviour of the erythrocyte deformability. This data highlights that the hemorheological alteration present in polycythemia vera has not been related to the increase of RBC mass only, as well as that present in plasmacellular dyscrasias has not been attributable to the increase of plasma viscosity only. The aim of this paper is to suggest some starting points for an accurate reflection, emphasizing the need of a revision of the current classification of primary hyperviscosity syndromes. [ABSTRACT FROM AUTHOR]

Optical Coherence Tomography Angiography (OCTA) is a relatively new imaging technique in ophthalmology for the visualization of the retinal microcirculation and other tissues of the human eye. This review paper aims to describe the basic definitions and principles of OCT and OCTA in the most straightforward possible language without complex mathematical and engineering analysis. This is done to help health professionals of various disciplines improve their understanding of OCTA and design further clinical research more efficiently. First, the basic technical principles of OCT and OCTA and related terminology are described. Then, a list of OCTA advantages and disadvantages, with a special reference to blood flow quantification limitations. Finally, an updated list of the basic hardware and software specifications of some of the commercially available OCTA devices is presented. [ABSTRACT FROM AUTHOR]

Purpose: Abdominal thromboses are a poorly characterized thrombotic complication of COVID-19. The aim of this paper is to report multimodality ultrasound imaging findings of the abdomen in evaluation of thrombotic lesions in hospitalized patients with COVID-19. Patients & Methods: In this retrospective observational study, patients admitted to a single University Hospital from April 1, 2020 to April 30, 2022, who tested positive for COVID-19 and developed acute abdominal pain over the course of hospitalization were included. Abdominal ultrasound imaging studies performed in these patients were reviewed, including B mode ultrasound (BMUS), color-coded Doppler ultrasound (CCDS) and contrast enhanced ultrasound (CEUS). Thromboembolic findings on contrast enhanced computed tomography (CTA) were also recorded. Results: Finally, 13 cases of abdominal thrombosis in 226 with COVID 19 infections were included (mean age, 56.69±8.97 years; 10 men, 3 women). Thromboembolic events included: iliac thrombosis (n = 4), portal venous (PV) thrombosis (n = 3), superior mesenteric vein (VMS) thrombosis (n = 2), inferior vena cava (IVC) thrombosis (n = 5) and inferior mesenteric vein (VMI) thrombosis (n = 1). In all cases of abdominal thrombosis, during high resolution BMUS scan, intra-luminary hypoechogenic appositional thrombi could be detected. Meanwhile blood flow with reduced speed less than 20 cm/s could be observed by CCDS. High arterial flow speed was a sign of collateral flow changes with diffuse venous dilatation. On CEUS, changes of the microcirculation of the liver, spleen, kidneys or small bowel by infarctions or micro-emboli could be detected. In 3 cases of PV thrombosis and in 2 cases of IVC thrombosis, catheter interventions were successful performed for recanalization without relevant lumen reduction afterwards. In other cases, without interventional procedure, partial recanalization happened with venous flow speed over 15 cm/s and lumen reduction more than 50%. Conclusions: Our study highlights those thromboembolic complications can be seen in hospitalized patients with COVID-19. Multimodality ultrasound examinations is helpful for early and accurate diagnosis of these complications. [ABSTRACT FROM AUTHOR]

BACKGROUND: In this paper, the method of steam vein occlusion for the treatment of the great/small saphenous vein (GSV/SSV) was analyzed in terms of a therapeutic influence on the dynamic parameters of global vein function, its effects on subjective symptoms based on chronic venous insufficiency (CVI) and the side effects of the steam vein sclerosis (SVS). It has been questioned whether the effects of this method lead to a recommendation for routine clinical practice. METHODS: The venous drainage and the venous refilling time (T0) of the leg treated were determined by photoplethysmography (Elcat, Wolfratshausen, Germany) before, six weeks and one year after the intervention to examine the effects on global venous function. Further changes of clinical symptoms and findings were assessed by the Venous Clinical Severity Score (VCSS), preoperatively and after one year, and the complication rate at 6-week follow-up was monitored. RESULTS: The SVS was performed on 167 veins (GSV: 124; SSV: 43) in a total of 156 patients. Eight patients (5.1%) did not attend the 6-week follow-up, while 29 patients (18.6%) were lost in the 1-year follow-up. Patients were suffering from symptoms such as leg pain and leg edema, which resulted in a VCSS of 9.4 (cumulated mean score of all patients) preoperatively. The T0 was reduced to mean values of 20.6 s (GSV cohort) and 21 s (SSV cohort). The VCSS improved to 6.0 after one year. This correlated with the hemodynamic parameters. The T0 increased in the GSV cohort after six weeks to 31.8 s, p < 0.001, and showed a nonsignificant improvement to 32.2 s, p = 0.509, in the 1-year check. The T0 also increased in the SSV cohort significantly after 6 weeks to 30.1 s, p < 0.001, and showed a nonsignificant reduction after one year, p = 0.289. A total of 71%of the GSV and 69.8%of the SSV of the patients involved no complications following the treatment. Light complications (grade 1) occurred (reddening, hematoma, hyperpigmentation) in the majority: 24.2%of the GSV and 18.6%of the SSV. We noticed one grade 3 complication with thrombosis in the SSV cohort, which led to a pulmonary embolism. Forty-seven complete questionnaires were analyzed (responder rate: 28.1%); 40.4%of the patients had light complaints after the treatment, such as pain, warmth or local pressure sensations (Fig. 7); 63%of those patients noticed only slight pain at a maximum of 3 out of 10. The majority (91%) would recommend this procedure. CONCLUSION: The SVS revealed endoluminal catheter-based intervention to abolish venous reflux of the G/SSV as safe. As one therapeutic target is to eliminate venous reflux, effectiveness of a method cannot be based on sonographic data alone; one must further assess patients' symptoms and dynamic venous function. This data shows an improvement of patients' symptoms which correlated well with the improvement of the venous function in digital photoplethysmography. The SVS can be recommended as a catheter-based treatment in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND: The incidence of postoperative microcirculatory flow alterations and their effect on outcome have not been studied extensively. OBJECTIVE: This systematic review and meta-analysis were designed to investigate the presence of sublingual microcirculatory flow alterations during the immediate and early postoperative period and their correlation with complications and survival. METHODS: A systematic search of PubMed, Scopus, Embase, PubMed Central, and Google Scholar was conducted for relevant articles from January 2000 to March 2021. Eligibility criteria were randomized controlled and non-randomized trials. Case reports, case series, review papers, animal studies and non-English literature were excluded. The primary outcome was the assessment of sublingual microcirculatory alterations during the immediate and early postoperative period in adult patients undergoing surgery. Risk of bias was assessed with the Ottawa-Newcastle scale. Standard meta-analysis methods (random-effects models) were used to assess the difference in microcirculation variables. RESULTS: Thirteen studies were included. No statistically significant difference was found between preoperative and postoperative total vessel density (p = 0.084; Standardized Mean Difference (SMD): –0.029; 95%CI: –0.31 to 0.26; I2 = 22.55%). Perfused vessel density significantly decreased postoperatively (p = 0.035; SMD: 0.344; 95%CI: 0.02 to 0.66; I2 = 65.66%), while perfused boundary region significantly increased postoperatively (p = 0.031; SMD: –0.415; 95%CI: –0.79 to –0.03; I2 = 37.21%). Microvascular flow index significantly decreased postoperatively (p = 0.028; SMD: 0.587; 95%CI: 0.06 to 1.11; I2 = 86.09%), while no statistically significant difference was found between preoperative and postoperative proportion of perfused vessels (p = 0.089; SMD: 0.53; 95%CI: –0.08 to 1.14; I2 = 70.71%). The results of the non-cardiac surgery post-hoc analysis were comparable except that no statistically significant difference in perfused vessel density was found (p = 0.69; SMD: 0.07; 95%CI: –0.26 to 0.39; I2 = 0%). LIMITATIONS: The included studies investigate heterogeneous groups of surgical patients. There were no randomized controlled trials. CONCLUSIONS: Significant sublingual microcirculatory flow alterations are present during the immediate and early postoperative period. Further research is required to estimate the correlation of sublingual microcirculatory flow impairment with complications and survival. [ABSTRACT FROM AUTHOR]

The coronary circulation is a complex system in which vascular resistances are determined by an interplay of forces in at least three compartments: the epicardial, the microvascular, and the venous district. Cardiologists, and particularly interventional cardiologists, normallly place the focus of their attention on diseases of the epicardial coronary circulation as possible causes of coronary syndromes and neglect the importance of the other two compartments of coronary circulation. The study of the coronary microcirculation, an increasingly recognized source of ischemia, has long been disregarded, but is witnessing a revival since the (re-)introduction of diagnostic tools in the better equipped catheterization laboratories. Unfortunately, to date our understanding of coronary microvascular disease remains incomplete and the numerous proposed classifications fail to reflect its complexity. Further, no specific therapy for these disorders is available. The coronary venous circulation is an even more neglected third vascular district. Its role in regulating coronary resistances is almost completely unexplored, but inital evidence suggests that the modulation of venous pressure might help improve coronary perfusion. Coronary sinus interventions are a group of invasive techniques (both surgical and catheter-based) that are designed to treat ischaemic heart disease by increasing coronary venous pressure and therefore redistributing coronary blood flow towards the endocardium. In this review paper, we revise the role of these interventions with particular focus on acute and chronic coronary microvascular disease. [ABSTRACT FROM AUTHOR]

In previous works, poly(D,L-lactide-co-εCL-poly(ethylene glycol) (poly(D,L-La-co-αPEGεCL) amphiphilic graftcopolymers were successfully synthesized according to a copper azide-alkyne cycloaddition (CuAAC) strategy. This paper aims at reporting on the behavior of this amphiphilic copolymer in water, which was not studied in the previous paper. Moreover, the ability of the copolymer to stabilize a PLA nanoparticles aqueous suspension is presented. For this purpose, dynamic light scattering (DLS) and transmission electron microscopy (TEM) are proposed to characterize the nanoparticles in solution. Otherwise, the strategy developed for the synthesis of the amphiphilic copolymers was adapted and extended to the synthesis of PLA-based degradable hydrogel, potentially applicable as drug-loaded degradable polymer implant. [ABSTRACT FROM AUTHOR]

Modeling blood coagulation has taken various directions in recent years, depending on the aspects that authors wish to emphasize. In this paper we want to address an issue that has been systematically ignored in the relevant literature, namely the effect of blood slip at the vessels wall. The presence of a slip results in an increased supply of activated platelets to the clotting site. We calculate such a contribution showing that, in extreme cases, it can be even dominant. Indeed, raising the concentration of activated platelets induces an acceleration of thrombin production and eventually of the whole clot progression. The model explains the difference between arterial and venous thrombi. We confine to the coagulation stage known as 'propagation phase' in the context of the so called cell based model. The paper is preparatory for a deeper analysis in which the clotting process is coupled to blood rheology and that will be carried out in the future by the same authors. At the present stage, the extremely complex biochemistry has been simplified adopting a leaner, though virtual, system of diffusion-convection-reaction equations, in the optics of providing 'modular' models, that can be reduced or enlarged so to meet specific modeling requirements. [ABSTRACT FROM AUTHOR]

There is evidence that changes in intravascular volume influence long-term cardiovascular events, and that this effect is independent of blood pressure. Using the Poiseuille–Hagen equation for laminar flow through a cylinder, assuming that blood pressure remains unchanged despite any change in intra-arterial volume, and assuming that blood in the large arteries has a constant viscosity, then it can be shown that the rate of arterial blood flow changes according to the equation Q2=Q1[1+(ΔV/VTI)]2, where Q1 represents the original rate of flow, Q2 represents the new rate of flow, ΔV represents the change in intra-arterial volume, and VTI represents the total intra-arterial volume. Furthermore, if one is willing to extrapolate from a single artery to the entire circulatory system, such that Q1 represents the initial cardiac output, Q2 represents the new cardiac output, ΔV represents the change in intravascular volume, and VTI represents the total intravascular volume, then it can be demonstrated that even small changes in intravascular volume have hemodynamic consequences. Specifically, an intra-arterial volume change of 2.7 cc will alter cardiac output by approximately 1% in the average human, with hemodynamic consequences comparable to a 1 mm change in the mean arterial pressure. The calculations in this paper suffer from a number of weaknesses, and there are justifiable reasons to consider the assumptions and extrapolations employed in this paper to be invalid or overly simplistic. Despite these limitations, the primary rationale for believing the assumptions and extrapolations to have merit is that the conclusions that result are consistent with, and help explain, a considerable amount of current research literature. Based upon these calculations, even small changes in intravascular volume would be expected to change the pressure on endothelial cells at arterial branch points and bifurcations, thereby influencing the development of atherosclerosis. [ABSTRACT FROM AUTHOR]

Physiological studies on fetal blood in narrow glass tubes have suggested that fetal optimal hematocrit (hct) might be as high as 60%. A theoretical 'ideal' hct can also be predicted with a theoretical curve of hematocrit/viscosity (h/η) ratio vs hct constructed with Quemada's model. We used the database of one of our previous papers on fetal hemorheology to reinterpret its results with this concept. A series of 28 intrauterine cord punctures (between 19 and 33 weeks gestation) with doppler measurements of resistance in umbilical arteries was studied. The theoretical 'optimal hematocrit' was well correlated to actual (r = 0.857, p < 0.01) but systematically lower (Bland-Altman plot +12.1[8.52-15.7]) than the actual one. Umbilical artery resistance index is correlated with actual hematocrit (r = 0.407, p < 0.05), the discrepancy between ideal and actual (r = -0.542, p < 0.05) but not predicted ideal hematocrit, suggesting that the discrepancy between ideal and actual may reflect an adaptative decrease aiming at reducing vascular resistance. These findings indicate that prediction of ideal hematocrit with Quemada's equation makes sense in fetal blood, and suggest that a 'viscoregulatory mechanism' maintains hematocrit below this theoretical value in order to avoid excess vascular resistance. [ABSTRACT FROM AUTHOR]

The ideal hematocrit is the hematocrit (Hct) value resulting in the highest value of Hct/viscosity (h/η) ratio and can thus be predicted from viscometric measurements with the use of equations such as Quemada's one which yield the determination of the bell-shaped curve of h/η as a function of Hct. In a series of recent papers we applied this approach to various populations, using viscometry at high shear rate (1000 s–1). However the shape of this curve has been reported to be dependent on the shear rate, resulting in a right-shift in this top value when Hct increase. We present here in 11 young recreative athletes the evolution of the predicted top of the h/η curve and optimal theoretical Hct and the discrepancy between theoretical and optimal values over the range of shear rates 1 to 6000 s–1. Results show that the predicted optimal value of both h/η and Hct increases when shear rate increases and that the discrepancy between predicted laquooptimalraquo and actual values decreases and becomes almost asymptotic at very high shear (500 s–1). It is minimal at 2720 s–1. The correlation between predicted laquooptimalraquo and actual values of both parameters describes the same evolution. Therefore, it is better for assessing h/η and its agreement with theoretical values, and for determining the theoretical ideal hematocrit, to measure blood viscosity at shear rates equal or superior to 500 s–1. [ABSTRACT FROM AUTHOR]

This paper investigates the use of computerized fractal analysis for objective characterization by means of transmission electron microscopy of the complexity of circulating platelets collected from healthy individuals and from type 2 diabetic patients, a pathologic condition in which platelet hyperreactivity has been described. Platelet boundaries were extracted by means of automatically image analysis. Local fractal dimension by box counting (measure of geometric complexity) was automatically calculated. The results showed that the platelet boundary observed by electron microscopy is fractal and that the shape of the circulating platelets is significantly more complex in the diabetic patients in comparison to healthy subjects (p < 0.01), with 100% correct classification. In vitro activated platelets from healthy subjects show an analogous increase of geometric complexity. Computerized fractal analysis of platelet shape by transmission electron microscopy can provide accurate, quantitative, data to study platelet activation in diabetes mellitus. [ABSTRACT FROM AUTHOR]

INTRODUCTION: In clinical setting, Sidestream Dark Field (SDF) imaging has provided unprecedented insights into the gut microcirculation mainly by studying the intestinal mucosa of patients with ileostomies. Visualizing microvascular structure and function of ileal mucosa at the bedside brings unique opportunity for clinical research, particularly in critically ill patients. Several papers that were focused on intestinal microcirculation, used different methods of assessment because an accepted scoring systems does not exist so far and it is no surprise that it is rather difficult to compare the results from these studies. The present paper presents recommendations concerning specific aspects of image acquisition and proposes some parameters for the description of the intestinal microcirculation in human studies, as suggested by the participants of a round table meeting. METHODS: The round table meeting participants reviewed all relevant literature, discussed various aspects of image acquisition by SDF technology in patients with ileostomy and parameters for the description of intestinal mucosa microcirculation. Selected key conditions for high quality and reproducible image recordings were identified. To evaluate quality of intestinal microcirculation, selected parameters and scoring system were suggested and described. RESULTS: For image acquisition in ileostomies, five key points were proposed: optimal timing, optimal SDF device probe positioning, optimal stabilization, optimal number and length of acquired video recordings, and optimal avoidance of pressure artefacts. With regard to image analysis, simplified set of quantitative and qualitative parameters for the description of the intestinal mucosa microcirculation for the clinical studies has been proposed: vessels per villus, microvascular flow index, proportion of perfused villi, and borders of villi. The proposed parameters can be included in a semi-quantitative scoring system; however, this scoring system needs further validation. This simplified analysis does not require sophisticated software and can be performed manually on the video screen. CONCLUSION: We propose a simple methodology for image acquisition and suggest specific microvascular parameters to analyze SDF imaging studies of the intestinal mucosa microcirculation in patients with ileostomy. Proposed scoring system needs to be validated in further clinical studies. [ABSTRACT FROM AUTHOR]

The focus of this paper is the determination of endothelial dysfunction in patients with metabolic syndrome (MetS) and the establishment of a relationship between the traditional biomarkers of endothelial dysfunction and the vascular tone regulation indices obtained from indirect cold tests in MetS patients. Our investigation was conducted on 30 patients aged 45.5±9 years. The control group comprised 14 healthy subjects aged 48.2±2.4 years. The mechanism of vascular tone regulation was investigated using the wavelet analysis of skin temperature oscillations (WAST). The degrees of microvascular vasoconstriction and vasodilatation were determined during contralateral cold tests in the endothelial (0.02–0.0095 Hz), neurogenic (0.05–0.02 Hz) and myogenic (0.05–0.14 Hz) frequency ranges. In MetS patients, vasoconstriction indices were higher and vasodilatation indices were lower than in the subjects of the control group, which is indicative of disorders in the mechanisms of microvascular tone regulation. These indices correlate with the metabolic parameters and VEGF (vascular endothelial growth factor) levels. The correlation of vasoconstriction and vasodilatation indices with the main factors of the metabolic syndrome testifies that the biological and functional aspects of the endothelial dysfunction are closely related. [ABSTRACT FROM AUTHOR]

BACKGROUND: In weightlessness, alterations in organ systems have been reported. The microcirculation consists of a network of blood vessels with diameters of a few μm. It is considered the largest part of the circulatory system of the human body and essential for exchange of gas, nutrients and waste products. An investigation of the microcirculation in weightlessness seems warranted but has not yet been performed. OBJECTIVE: In this paper, we outline a study in which we will investigate the possible interrelations between weightlessness and microcirculation. We will induce weightlessness in the course of parabolic flight maneuvers, which will be conducted during a parabolic flight campaign. In this study protocol also an evaluation of a possible influence of parabolic flight premedication on microcirculation will be described. METHODS: The microcirculation will be investigated by sublingual intravital measurements applying sidestream darkfield microscopy. Parameters of macrocirculation such as heart rate, blood pressure and blood oxygenation will also be investigated. RESULTS: In our pre-study experiments, neither dimenhydrinate nor scopolamine altered microcirculation. CONCLUSIONS: As the application of motion sickness therapy did not alter microcirculation, it will be applied during the parabolic flight maneuvers of the campaign. Our results might deepen the understanding of microcirculation on space missions and on earth. [ABSTRACT FROM AUTHOR]

The aim of this study was the evaluation of the erythrocyte deformability in multiple myeloma (MM). We enrolled 29 MM patients and we evaluated, on fasting venous blood, the erythrocyte deformability, expressed as elongation index, and examined using the diffractometric method. By comparing normal controls and MM patients, a significant decrease in erythrocyte deformability, especially at low shear stresses, was found. In this research paper we evaluated all the hypothesis for a possible explanation of the behaviour of red blood cell deformability in MM, even considering how the alteration of erythrocyte deformability worsens the microcirculatory flow in these patients in association with the marked increase in plasma viscosity. [ABSTRACT FROM AUTHOR]

In surgical pathophysiology ischemia-reperfusion, inflammatory processes, sepsis, vascular interventions, tissue trauma, shock, all mean conditions in which hemorheological parameters show alterations. Despite of numerous clinical and experimental studies, the in vivo hemorheology is not completely understood yet, and several fundamental questions still need to be answered. Investigating these issues, experimental surgical models are important, in point of view of the translational research as well. In this paper we aimed to make an attempt on summarizing the possible factors and conditions that might have an effect on hemorheological results in experimental surgical studies. Hemorheological parameters show alterations in surgical pathophysiological processes in a complex way. However, the changes are dominantly non-specific. Standardized experimental conditions, related to the experimental animal (species, animal welfare) anesthesia-medications, operation, sampling and, if applicable, conditions of the postoperative period, are inevitable for a safe assessment of valuable (hemorheological) results. Parallel investigations – such as microcirculatory monitoring, imaging techniques, other laboratory methods, histomorphology– have great importance, together with individual analysis of changes, for a better understanding of the changes and for comparability with clinical results. [ABSTRACT FROM AUTHOR]

Fluid retention increases intravascular volume and pressure. The calculations in this paper demonstrate that fluid retention increases the likelihood that blood will flow in a turbulent manner, in part due to an increase in stroke volume, regardless of whether or not blood pressure is increased. Increased turbulence will promote endothelial dysfunction, thereby contributing to the development of atherosclerotic cardiovascular disease. Accordingly, fluid retention is predictably detrimental to the cardiovascular system. The reason that some medications, such as cyclo-oxygenase-2 inhibitors, nonselective nonsteroidal anti-inflammatory drugs, estrogens, progestins, and rosiglitazone, are associated with an increased risk of myocardial infarcts and strokes may be that they cause fluid retention. Increased stroke volume and/or edema formation may indicate that a medication increases the risk of adverse cardiovascular events. For drugs that increase the risk of adverse cardiovascular events, it may be possible to reduce or neutralize the increased risk by simultaneously administering a diuretic. [ABSTRACT FROM AUTHOR]

Nitroglycerin (GTN) has been shown, in both human and animal studies, to induce a protective phenotype that limits tissue damage after ischemia and reperfusion. This phenomenon is similar to ischemic preconditioning, and several reports suggest that also the molecular pathways involved in this protective effect of nitrates are the same that determine ischemic preconditioning. Our group conducted a series of studies aimed at investigating, using a human model of endothelial IR injury, the mechanism of nitrate-induced preconditioning and particularly the role of reactive oxygen species formation and of the opening of mitochondrial permeability transition pores. Our data demonstrate that GTN protects the endothelium against postischemic endothelial dysfunction in a mechanism that is mediated by oxygen free radical release and opening of mitochondrial permeability transition pores. In contrast, the protective effect of pentaerithrityl tetranitrate appears to be independent of these mechanisms, and it seems to be mediated by induction of antioxidant genes. Finally, isosorbide mononitrate seems to be devoid of a significant protective effect. These data are summarized and discussed in the present paper. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to provide a scientific basis for a unified standard of the reference value of old people's hematocrit in China. The reference values of healthy old people's hematocrit have been collected according to the Wintrobe methods; the relationship between the reference values of old people's hematocrit and altitude has been tested in this paper. It has been found that the reference value of old people's hematocrit increases when the altitude gradually increases, and such relationship is quite significant. The method of mathematical univariate regression analysis is used to deduce two regression equations: $\widehat{Y}$[sub 1] =44.1+0.00351x±4.5, $\widehat{Y}$ [sub 2] =39.5+0.00298x±4.1. If the altitude value of a particular area of China is known, the reference value of old people's hematocrit there can be calculated by means of the regression equations. Furthermore, depending on the altitude, China can be divided into three districts: Qingzang District, Central District and Eastern District. [ABSTRACT FROM AUTHOR]

This paper aimed to evaluate the significance of nitric oxide (NO) in the physiology of the penis. Pudendal arteries and penile cavernous tissue of the Macaca nemestrina pertaining to NO were examined in the view of molecular biology and physiology. The results showed that potential resources of NO were in the neuron, sinusoidal endothelium and corporal smooth muscle cells of the penis. NO exerted a host of functional roles by binding with specific molecular targets. It was concluded that NO exerts a significant role in physiology, especially in the microcirculation of the penis, as the principal mediator of erectile function. [ABSTRACT FROM AUTHOR]

INTRODUCTION: In the field of cardiovascular diseases an ergometer test is a common diagnostical method in which a change in microcirculation can be reached. In this paper cardiac frequency and cutaneous microcirculation during and after exercising will be compared with each other. MATERIALS AND METHODS: The cutaneous microcirculation of 6 healthy volunteers (2 females, 4 males) is measured. As an instrument the PeriFlux 5000 combined with a Laser-Doppler-Flow(LDF)-Probe (Perimed Instruments) is used. The cardiac frequency (CF) is measured by the POLAR T31 sensor and as an ergometer the ERGO-FIT® 457 is used. RESULTS: The mean initial LDF (97,7±57,3 PU) decreases at the beginning (64,5±21,7 PU), increases during the exercise, reaches its maximum (247,8±82,1 PU) after the end of the exercise and drops to lower values (256,4±69,5 PU) after a few minutes. Contrasting to the LDF the mean initial CF (86±22/min) increases at the beginning (97±9/min), furthermore during the whole exercise (103±9/min) and then falls after having finished the exercise (96±3/min). Furthermore, during regeneration, one can see the CF decreasing towards its initial value, while LDF reaches its maximum. CONCLUSION: In further studies, realized with volunteers with well-known levels of physical condition, a direct connection between cutaneous microcirculation and physical condition might be found. [ABSTRACT FROM AUTHOR]

Patients suffering from diabetes or hypertension commonly exhibit increased blood viscosity compared with healthy controls. This is primarily the result of elevated plasma fibrinogen concentration. Cigarette smokers also exhibit raised blood viscosity but in their case the main cause is a raised haematocrit. In this paper the effects of concurrent hypertension, diabetes and cigarette smoking on blood viscosity is reviewed. Evidence is presented that the haemorheological disturbances associated with each of these modalities are additive when present together in a subject. [ABSTRACT FROM AUTHOR]

The article discusses the importance of microcirculation as the platform to reveal the mechanism of diseases. The author defined angiogenesis as the growth of new blood vessels, which is also considered important due to its natural process occurring in the body, both in health and in disease. In addition, he also cited that microvasculature has become a key target for proteomics.

Most human tissues do not regenerate spontaneously, which is why "cell therapy" are promising alternative treatments. The Principe is simple: patients' or donors' cells are collected and introduced into the injured tissues or organs directly or in a porous 3D material, with or without modification of their properties. This concept of regenerative medicine is an emerging field which can be defined as "the way to improve health and quality of life by restoring, maintaining, or enhancing tissue and organ functions". There is an extraordinarily wide range of opportunities for clinical applications: artheropathies, diabetes, cartilage defects, bone repair, burns, livers or bladder regeneration, organs reconstruction (lung, heart, liver . . . ) neurodegenerative disorders, sepsis . . . Different stem cells (SC) with different potential can be used and characterised (totipotent, mesenchymal of different origins, especially those present in tissues. . . ). Today it is undeniable that cells like bone marrow, adipose tissue or Wharton Jelly stem cells, are of potential interest for clinical applications because they are easily separated and prepared and no ethical problems are involved in their use. In this paper some potential clinical applications in the vascular field are considered: peripheral arteriopathy in diabetic patients, cardiac insufficiency, traitment of erectile dysfunction, or organ regeneration with liver as example. But the regeneration of tissue or organ is and will remain a challenge for the future development of cell therapy. Many problems remain to be solved that could lead to the development of innovative strategies to facilitate cell differentiation, increase the yield of cells and ensure a standardised product, overcome the risks of teratogenic effects and/or immune reactions, enable grafting via direct cell or biotissue transplantation and avoid legal issues involved in national regulations. [ABSTRACT FROM AUTHOR]

An obvious candidate for the seminal event in the history of haemorheology is Harvey's presentation of the concept of the circulation of the blood. Prior to this, the ideas concerning the movement of blood were based, in Europe and Middle East, largely on the principles laid down by Galen, and these had been, in effect, dogma for nearly a millennium and a half. These principles were basically that blood is formed in the liver, thence it travels to the bodily organs and is consumed - hence there is one-way flow and no circulation of the blood at all. Harvey's revolutionary idea that blood circulates repeatedly around the cardiovascular system laid the foundation for haemorheology because once that idea was accepted then the fluidity of the blood immediately became potentially of crucial importance - and haemorheology was conceived. In this paper the ideas that preceded Harvey will be presented, i.e. those of Galen, Ibn al-Nafis, Vesalius, Fabricius and Colombo etc. Harvey's awareness of this background, due mainly to time spent in Padua, triggered his many experimental investigations and discoveries. Ultimately, these led to his astonishing insights published in De Mortu Cordis in 1628 which changed the understanding of the cardio-vascular system forever. [ABSTRACT FROM AUTHOR]

Rheopheresis is an extracorporal selective double-filtration procedure. In the first part of the treatment the blood is passes through the plasma filter, which separates blood cells from the plasma. Then the plasma flow to a second filter called MONET (Membranefiltration Optimised Novel Extracorporal Treatment). The MONET filter retains high molecular weight proteins such LDL, Lp(a), fibrinogen, α2 macroglobulin, vWF and IgM. Hereby the whole blood and plasma viscosity decrease, improves microcirculation, and has a positive effect on lipid profile as well. Accorging to ASFA recommendation rheopheresis is a first line treatment in age-related dry macular degeneration and in sudden sensorineural hearing loss. There are other clinical situations in which rheopheresis has been used effectivly. But only few data are available and large clinical trials have not been done in these diseases. In this paper we describe a case history and laboratory findings of a patient who suffers from age related dry macular degeneration and was successfully treated by rheopheresis. [ABSTRACT FROM AUTHOR]

Red blood cell rheology and adhesiveness play a key role in the occurrence of vaso-occlusive like events in sickle cell anemia. The present paper reviews counter-intuitive findings supporting that rigid and serrated sickle red blood cells do not initiate vaso-occlusion. Instead, the less rigid red blood cells could initiate vaso-occlusion because of their increased adhesiveness to the vascular wall. We suspect that stiffness of sickle erythrocytes and the topography of RBC membrane are factors affecting adhesion to the endothelium. [ABSTRACT FROM AUTHOR]

Wall shear stress (WSS) is a very important hemodynamic parameter implicated in many physiological and pathological phenomena. In order to study these phenomena, it is more convenient to use in vitro models before testing on animals and humans. Dynamic in vitro cerebrovascular models are considered capable of simulating the in vivo hemodynamic conditions, but only few of them seem to meet the criteria for this task. It is now clear that in the human eye microcirculation a significant pulsation exists at the pre-capillary arterioles with average WSS values more than twice those in the venular side, for the same diameters. WSS heterogeneity is in support of segmental heterogeneity i.e. the endothelial phenotypic and functional difference among arterioles, capillaries and venules. In this review paper, the importance of WSS is described in detail and two more microvascular segments are proposed: a pre-capillary arteriolar and a post-capillary venular segment. The accurate hemodynamic simulation in all microvascular segments seems to be a prerequisite step in the development of dynamic in vitro blood brain barrier (BBB) models and microfluidic platforms on chip. Endothelial cells in the cardiovascular system seem to have sophisticated role acting like cardiovascular processing sensors (CPSs). [ABSTRACT FROM AUTHOR]

The incidental finding of a liver lesion with basic ultrasound is one of the most common clinical issues. Some of the liver lesions which present typical morphological B-mode features (e.g. cysts, typically localized focal fatty sparing/ accumulations, hyperechoic hemangiomas) can be easily diagnosed by conventional ultrasound without the need of further diagnostic procedures. Others frequently necessitate further investigation with contrast-enhanced imaging techniques or biopsy in order to differentiate benign from malignant lesions and obtain a final diagnosis. This paper will discuss differences between vascular phases of different cross-sectional contrast-enhanced methods, as well as their subsequent benefits for focal liver lesions (FLLs) assessment, adding also a particular emphasis on small FLLs detection and characterization. [ABSTRACT FROM AUTHOR]

Standard of care in the therapy of chronic venous insufficiency (CVI) is the use of graduated elastic stockings (GECS). This paper is based on a prospective, mono-centric, open randomised, controlled and cross over study and discusses the hemodynamic effects of GECS and inverse graduated compression stockings (PECS) in 32 healthy volunteers and 32 patients with CVI and the consecutive impact on comfort. The application of stockings was performed sequentially, the allocation of the first stocking was randomized and double blind, wearing period for each stocking type about 7 days with one week of break between wearing periods. Measurements of the interface pressure were carried out by Picopress®(Microlab Elettronica, Italy) and the venous drainage were registered by strain gauge plethysmography. Mean interface pressure: GECS (level B1): 27.3 mmHg; GECS (level C): 19,6 mmHg; PECS (level B1): 17,8 mmHg; PECS (level C): 24,7 mmHg. Significant increase of EF and decrease of VFI by wearing both types of compression stockings, comparatively GESC resulted in a significantly greater improvement of EF than the PECS. PECS were significantly easier to don and put on compared to the GECS, the PECS tended to slip towards the foot more often. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pregnancy is a dynamic process associated with changes in vascular and rheological resistance. Maternal maladaptation to these changes is the leading cause of pregnancy complications such as preeclampsia. OBJECTIVE: This study aimed to assess the hemorheological alterations in pregnancies with a high risk for preeclampsia in the first trimester. METHODS: Ninety-two pregnant women were allocated into the high preeclampsia risk group (37 cases) and control groups (55 cases). Plasma and whole blood viscosity and red blood cell morphodynamic properties, including deformability and aggregation were assessed by Brookfield viscometer and laser-assisted optical rotational cell analyzer (LORRCA) at 11–14 gestational weeks. RESULTS: Whole blood viscosity was significantly higher in the high-risk group at all shear rates. Plasma viscosity and hematologic factors showed no differences between the groups. Hematocrit levels positively correlated with high blood viscosity only in the high-risk group. There were no significant changes in the other deformability and aggregation parameters. CONCLUSIONS: Changes in the whole blood viscosity of pregnant women with high preeclampsia risk refer to impaired microcirculation beginning from the early weeks of gestation. We suggest that the whole blood viscosity is consistent with the preeclampsia risk assessment in the first trimester, and its measurement might be promising for identifying high-preeclampsia-risk pregnancies. [ABSTRACT FROM AUTHOR]