Increased Blood Viscosity Research Articles

Visualizing Sickle Cell Disease Whole Blood Flow and Viscosity through Modifications to Hemoglobin Levels from a Simple Blood Transfusion

Red cell transfusions are an effective part of a clinical care regiment in the treatment of chronic sickle cell disease; however, the understanding of the target hemoglobin levels has not been investigated past the standard hematocrit/hemoglobin (HgB) of 10 g/dL. A simple transfusion of packed red cells can be a beneficial clinical treatment of acute pain crisis or even stroke. Along with other transfusion-based complications, when performing a simple transfusion, the changes in blood velocity as a result of increased blood viscosity from the additional red cells can lead to complications of their own. Because of this, clinical treatment has hesitated to transfuse sickle patients above a HgB of 10 g/dL.The complications of sickle cell disease tend to be more pronounced on the microvascular scale than then macrovascular. Along with this, the overall slower blood flow caused by the increase in viscosity from a simple blood transfusion is more probable to lead to complications on the microvascular level. Our device allows us to target the changes in whole blood on multiple scales including down to arteriole sizes. Here, we have begun to investigate how transfusion could be more patient-specific by identifying the velocity profile of whole blood flowing through a “microvasculature-on-a-chip” device that mimics the microvascular geometry (Figure 1A). The devices were microfabricated using polydimethylsiloxane (PDMS) and then coated with 0.1% bovine serum albumin (BSA) to help prevent red cell adhesion to channel walls. To simulate various HgB levels, healthy whole blood samples were centrifuged to separate red cells. To simulate a simple clinical transfusion of a sickle patient, isolated red cells were added to sickle whole blood samples. Similar to a clinical setting, sickle samples were only transfused up to higher HgB levels. HgB levels were then confirmed on a differential hematology analyzer (Sysmex XN 330). 3.2mm CA+ was added to various HgB samples to defeat the citrate anticoagulant. Samples were loaded into syringes then perfused into the BSA coated devices (Figure 1B).During perfusion, a 450 frame video of flow was captured at 40x resolution and 163 fps. Following capture, videos parameters such as frame rate and pixel distance were defined in a custom MATLAB (Mathworks, Natick, MA) script. The script segmented videos into cropped frames of the desired regions of interest then a Kanade-Lucas-Tomasi (KLT) tracking algorithm detected red cell features in each frame across 4 frames (Figure 1 B&C). 12 equal spaced bins were created across the width of the channel in the direction of flow; Tracked velocities were assigned to their corresponding bin and averaged to create a velocity profile of function as the distance from the center of the channel (Figure 1 D&E).To create a case study, two patient samples were received with the same starting HgB of 6.8 g/dL and were transfused upwards incrementally to a HgB of 12 g/dL. One patient is currently on a hydroxyurea regiment and the other patient is not. At each HgB level, the perfused whole blood was tracked through several different arteriole-sized vessels (30, 40 & 60 um) at two appropriate flow rates. To quantify the differences in the flow, the average cell velocity (um/s) through the channel and the peak velocity (um/s) through channels were charted against the various HgB levels (Figure 2).Continuing this series of experiments, 2 additional sickle whole blood on hydroxyurea samples were transfused upwards from their respective starting hemoglobin (9.7 & 10 g/dL). The flow was tracked and averages were quantified across the channel through its distance from the center of the channel. As transfused sickle HgB levels were increased, the bluntness of the velocity profile, or the difference between the average flow velocity in the center of the channel and at the walls of the channel, became less dramatic. This could be primarily attributed to the increase in the viscosity from the addition of the red cells (Figure 3).Our data shows that viscosity plays an important factor in whole blood flow. HgB of 10 g/dL is an important target for sickle transfusions; however, this target HgB may be more patient-specific than previously stated. Understanding patient viscosity may prove to be more important than hemoglobin levels. As patient blood increases in viscosity, blood slows down on the microvascular level the most. This may be critical in understanding the appropriate transfusion. [Display omitted] DisclosuresLam: Sanguina, Inc.: Current holder of individual stocks in a privately-held company. Kemp: Parthenon Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Pathophysiological bases of maladjustment formation in high mountains and polar zones

The pathophysiological features of the development of maladjustment under mountain-cold conditions as a manifestation of the syndrome of mutual burdening are considered. In this study, contents of various literary sources, characterizing a persons resistance to the effects of a complex of factors under high mountains and polar zones conditions, were analyzed. With the simultaneous exposure to hypoxia and hypothermia from a pathophysiological point of view, intersecting links of terminological paths, often having diametrically opposite dynamics of changes in the characterized concepts, will be significant. Thus, in the terminological mitochondrial pathway of energy metabolism, uncoupling proteins are present, which, to increase the resistance to hypothermia, should be activated to switch the energy metabolism to predominantly use fatty acids. However, hypoxic conditions should be suppressed to maintain the level of adenosine triphosphate acid available for cells. In the terminological tract of compensatory reactions in response to hypoxemia, the volume of pulmonary ventilation is released, which must increase to improve tolerance to hypoxia, which, under mountain-cold conditions, increased heat loss and promote the deterioration of the condition, i.e., tolerance to low temperatures. Under hypoxic and hypothermic conditions, a synergistic interaction can form, which can be manifested by the development of a syndrome of mutual burdening, which will result in a significant decrease in the functional capabilities of the body, result, and productivity. Maladjustment to mountain cold, with maximum probability, will manifest as disorders of the central nervous system, decreased physical performance, depletion of the functional and regulatory reserves of the body, functional immunodeficiency, decreased regenerative potential, and development of endogenous intoxication. With a high degree of probability, a significant synergistic interaction of hypoxia and hypothermia can be found in relation to the indicators of pulmonary ventilation, blood gases (hypercapnia), acidbase balance (gas alkalosis and lactic acidosis), heart rate (tachycardia), blood pressure (hypotension), central venous pressure (increase), blood viscosity (increase) and its coagulability (hypercoagulation), peroxide and free radical oxidation (activation), and protein catabolism (increase). These changes will negatively affect the functional state of specialists performing complex professional tasks in polar latitudes.

Leukostasis aggravated by red blood cell transfusion in a chronic lymphocytic leukemia patient

Abstract Introduction/Objective Leukostasis/symptomatic hyperleukocytosis is commonly seen in acute leukemias and is characterized by high blast counts and symptoms of decreased tissue perfusion with a one-week mortality of 20-40%, if left untreated. It is a rare complication in chronic lymphocytic leukemia (CLL) and is seen in CLL patients with white blood cell (WBC) counts > 500x10^9/L. Studies have shown that transfusion of blood products prior to decreasing the WBC count may lead to increased blood viscosity and worsen leukostasis. We report a CLL patient with a lower WBC count presenting with symptoms of leukostasis, further worsened by a red blood cell (RBC) transfusion prior to leukapheresis. Methods/Case Report A 73-year-old male with history of CLL for 5 years, hypertension and chronic kidney disease presented with acute dyspnea for 1 day. The WBC count was 208x10^9/L, hemoglobin was 6.5 g/dL, troponin I was 1.554 ng/mL, creatinine was 1.68 mg/dL and chest x-ray showed bilateral interstitial lung edema. The patient was diagnosed with acute hypoxic respiratory failure, acute kidney injury and myocardial infarction due to leukostasis. He received RBC transfusion, shortly after which his dyspnea worsened. There were no other signs or symptoms that could suggest a transfusion reaction. A single leukapheresis was performed following which there was a significant improvement in symptoms with a drop in WBC count to 123.1x10^9/L and creatinine to 1.3 mg/dL. Results (if a Case Study enter NA) NA Conclusion CLL may present with symptomatic hyperleukocytosis at lower leukocyte counts than has been described in the literature. Symptoms due to leukostasis can be precipitated/worsened by transfusion of blood products due to increased blood viscosity. It is critical to identify the signs and symptoms of this medical emergency as prompt diagnosis and management with leukapheresis significantly reduces the leukocyte count and blood products should be transfused slowly during or after leukapheresis.

Plasma D-Dimer Level Correlates with Age, Metastasis, Recurrence, Tumor-Node-Metastasis Classification (TNM), and Treatment of Non-Small-Cell Lung Cancer (NSCLC) Patients.

Plasma D-Dimer Level Correlates with Age, Metastasis, Recurrence, Tumor-Node-Metastasis Classification (TNM), and Treatment of Non-Small-Cell Lung Cancer (NSCLC) Patients.

Chronic thromboembolic pulmonary hypertension in an obese patient with type 2 diabetes mellitus

Metabolic disorders represent a serious medical and social problem and are risk factors for the development of thromboembolic complications. Disturbances of both carbohydrate and fat metabolism contribute to an increase in blood viscosity, creating prothrombotic conditions, which are not always objectively assessed even by specialists. In addition, multiple comorbid conditions usually significantly complicate the prognosis. The article presents a clinical case of recurrent thrombosis of the right atrium and the orifices of the superior and inferior vena cava in a 39-year-old patient with type 2 diabetes mellitus, obesity, arterial hypertension, and varicose vein disease.

Effect of Diabetes Mellitus and Hypertension on Osmotic Fragility and Hemorheological Factors in Male Wistar Rats

Diabetes mellitus is a common risk factor for erythrocyte osmotic stress. This study was aimed at exploring the effect of streptozotocin (STZ)-induced diabetes mellitus and salt-induced hypertension on osmotic fragility and hemorheological variables in male Wistar rats. Thirty male rats were grouped into five groups of six animals each as follows: negative control (zero salt in diet); positive control (normal salt diet - 0.3% salt); high salt diet (8% salt) (HSD only); STZ induced diabetes and normal salt diet (STZ only); STZ induced diabetes and high salt diet (STZ + HSD). At the end of a 4 weeks period, hematological variables, osmotic fragility, rheology and cardiovascular responses were assessed. There was an increase (p<0.05) in the mean arterial pressure and heart rate of HSD, STZ and HSD + STZ groups indicating a salt induced hypertension. There was a decrease in the body weight of STZ and HSD +STZ groups. There was significant increase (p<0.05) in the haematocrit, platelets estimates and fibrinogen concentrations in the experimental groups when compared with the controls. The STZ and STZ + HSD groups showed a reduced clotting time which corresponded to the increased platelet estimates and fibrinogen concentration. The increase in haematocrit, platelet and plasma protein resulted in the increased blood viscosity and a decreased flow rate. The osmotic fragility test was also observed to be increased (p<0.05) in HSD, STZ only and STZ + HSD groups. Diabetes mellitus and hypertension increase the rate of hemolysis of erythrocyte, as well as increase blood viscosity.

Response to case report on myocarditis and pericarditis after COVID-19 vaccination.

We would like to comment on the publication “Myocarditis and pericarditis after vaccination for COVID-19.” Hudson et al reported on an interesting case study and concluded that, “Although the majority of reported cases are coming from the lay press as the number of reports increases there is growing concern for at least an association between COVID-19 vaccination and subsequent myocarditis.” 1 Hudson et al showed clinical data to support the existence of the cardiac problem. In the present case, a presumptive diagnosis of myocarditis is based on clinical history and laboratory findings. No cardiac imaging or pathological study is done. Based on the case report, the cardiac problem is confirmed, but the pathogenesis of the cardiac problem is not clear. Hudson et al discussed many potential mechanisms of the cardiac problem, including hypersensitivity, inflammatory process, or inappropriate immune activation.1 We agree that immunopathological processes might induce the problem. However, no laboratory evidence exists to confirm this. If there is a hypersensitivity problem, some basic laboratory findings, such as eosinophilia or basophilia, should be observed. For inflammatory process, there should be increased leukocyte count and elevated erythrocyte sedimentation rate. For inappropriate immune response, autoimmunity should be detected. Another possible explanation is hyperviscosity-induced cardiac problem.2 After vaccination, excessive increased blood viscosity might occur and it might cause further cardiac problems.3 The underlying mechanism of post COVID-19 vaccination hyperviscosity is a change of antibody level in plasma after vaccine stimulation. In the case of underlying high blood viscosity or previous COVID-19, the excessive increasing of antibody level might occur and can result in excessive blood viscosity and hyperviscosity.2, 3 Because hyperviscosity is a hypercoagulable state, there might be a clot and thrombosis of the heart and it can further result in acute myocarditis.4

Rheological Impact of GBT1118 Cessation in a Sickle Mouse Model.

In sickle cell disease (SCD), higher whole blood viscosity is a risk factor for vaso-occlusive crisis, avascular necrosis, and proliferative retinopathy. Blood viscosity is strongly impacted by hemoglobin (Hb) levels and red blood cell (RBC) deformability. Voxelotor is a hemoglobin S (HbS) polymerization inhibitor with anti-sickling properties that increases the Hb affinity for oxygen, thereby reducing HbS polymerization. In clinical trials, voxelotor increased Hb by an average of 1g/dl, creating concern that this rise in Hb could increase viscosity, particularly when the drug was cleared. To investigate this potential rebound hyperviscosity effect, we treated SCD mice with GBT1118, a voxelotor analog, and stopped the treatment to determine the effect on blood viscosity and RBC deformability under a range of oxygen concentrations. GBT1118 treatment increased Hb, improved RBC deformability by increasing the elongation index under normoxic (EImax) and hypoxic conditions (EImin), and decreased the point of sickling (PoS) without increasing blood viscosity. The anti-sickling effects and improvement of RBC deformability balanced the effect of increased Hb such that there was no increase in blood viscosity. Forty-eight hours after ceasing GBT1118, Hb declined from the rise induced by treatment, viscosity did not increase, and EImin remained elevated compared to control animals. Hb and PoS were not different from control animals, suggesting a return to native oxygen affinity and clearance of the drug. RBC deformability did not return to baseline, suggesting some residual rheological improvement. These data suggest that concerns regarding viscosity rise above pre-treatment levels upon sudden cessation of voxelotor are not warranted.

English

Chronic kidney disease (CKD) is becoming a major health concern due to its increasing incidence among adults. There are few studies that suggest the possible relation between hearing loss and chronic kidney disease. So far only a small number of large population - based studies have assessed the relation between CKD and hearing loss. The global prevalence of CKD was 9.1 % (697.5 million cases) in 2017. The age and sex wise global prevalence of CKD was higher in women (9.5 %) than in men (7.3 %). In India, prevalence of sensorineural hearing loss (SNHL) is around 28 % to 77 % among CKD patients. Studies found that the incidence was 77 % for mild to very mild hearing loss and the incidence was 46 % for moderate to severe hearing loss. Various theories behind SNHL in CKD patients are structural similarity between ear and kidney, increased blood viscosity because of hypertension and finally electrolyte imbalance which are all thought to play a role in development of SNHL in CKD patients. Major risk factors for SNHL in CKD patients are duration of CKD, hypertension, diabetes mellitus, serum urea and creatinine levels, electrolyte imbalance, packed cell volume (PCV), ototoxic drugs. CKD being a long-term illness and majority of cases of SNHL in CKD patients are permanent, it has a great negative impact on the patient’s quality of life adding to the disability burden.

Implication of Blood Rheology and Pulmonary Hemodynamics on Exercise-Induced Hypoxemia at Sea Level and Altitude in Athletes.

This study aimed to investigate the changes in blood viscosity, pulmonary hemodynamics, nitric oxide (NO) production, and maximal oxygen uptake (V˙O2max) during a maximal incremental test conducted in normoxia and during exposure to moderate altitude (2,400m) in athletes exhibiting exercise-induced hypoxemia at sea level (EIH). Nine endurance athletes with EIH and eight without EIH (NEIH) performed a maximal incremental test under three conditions: sea level, 1 day after arrival in hypoxia, and 5 days after arrival in hypoxia (H5) at 2,400m. Gas exchange and oxygen peripheral saturation (SpO2) were continuously monitored. Cardiac output, pulmonary arterial pressure, and total pulmonary vascular resistance were assessed by echocardiography. Venous blood was sampled before and 3min after exercise cessation to analyze blood viscosity and NO end-products. At sea level, athletes with EIH exhibited an increase in blood viscosity and NO levels during exercise while NEIH athletes showed no change. Pulmonary hemodynamics and aerobic performance were not different between the two groups. No between-group differences in blood viscosity, pulmonary hemodynamics, and V˙O2max were found at 1 day after arrival in hypoxia. At H5, lower total pulmonary vascular resistance and greater NO concentration were reported in response to exercise in EIH compared with NEIH athletes. EIH athletes had greater cardiac output and lower SpO2 at maximal exercise in H5, but no between-group differences occurred regarding blood viscosity and V˙O2max. The pulmonary vascular response observed at H5 in EIH athletes may be involved in the greater cardiac output of EIH group and counterbalanced the drop in SpO2 in order to achieve similar V˙O2max than NEIH athletes.

Erythropoietin and derivatives: Potential beneficial effects on the brain.

Erythropoietin (Epo), the main erythropoiesis-stimulating factor widely prescribed to overcome anemia, is also known nowadays for its cytoprotective action on non-hematopoietic tissues. In this context, Epo showed not only its ability to cross the blood-brain barrier, but also its expression in the brain of mammals. In clinical trials, recombinant Epo treatment has been shown to stimulate neurogenesis; improve cognition; and activate antiapoptotic, antioxidant, and anti-inflammatory signaling pathways. These mechanisms, proposed to characterize a neuroprotective property, opened new perspectives on the Epo pharmacological potencies. However, many questions arise about a possible physiological role of Epo in the central nervous system (CNS) and the factors or environmental conditions that induce its expression. Although Epo may be considered a strong candidate to be used against neuronal damage, long-term treatments, particularly when high Epo doses are needed, may induce thromboembolic complications associated with increases in hematocrit and blood viscosity. To avoid these adverse effects, different Epo analogs without erythropoietic activity but maintaining neuroprotection ability are currently being investigated. Carbamylated erythropoietin, as well as alternative molecules like Epo fusion proteins and partial peptides of Epo, seems to match this profile. This review will focus on the discussion of experimental evidence reported in recent years linking erythropoietin and CNS function through investigations aimed at finding benefits in the treatment of neurodegenerative diseases. In addition, it will review the proposed mechanisms for novel derivatives which may clarify and, eventually, improve the neuroprotective action of Epo.

Global REACH 2018: the adaptive phenotype to life with chronic mountain sickness and polycythaemia.

Humans suffering from polycythaemia undergo multiple circulatory adaptations including changes in blood rheology and structural and functional vascular adaptations to maintain normal blood pressure and vascular shear stresses, despite high blood viscosity. During exercise, several circulatory adaptations are observed, especially involving adrenergic and non-adrenergic mechanisms within non-active and active skeletal muscle to maintain exercise capacity, which is not observed in animal models. Despite profound circulatory stress, i.e. polycythaemia, several adaptations can occur to maintain exercise capacity, therefore making early identification of the disease difficult without overt symptomology. Pharmacological treatment of the background heightened sympathetic activity may impair the adaptive sympathetic response needed to match local oxygen delivery to active skeletal muscle oxygen demand and therefore inadvertently impair exercise capacity. Excessive haematocrit and blood viscosity can increase blood pressure, cardiac work and reduce aerobic capacity. However, past clinical investigations have demonstrated that certain human high-altitude populations suffering from excessive erythrocytosis, Andeans with chronic mountain sickness, appear to have phenotypically adapted to life with polycythaemia, as their exercise capacity is comparable to healthy Andeans and even with sea-level inhabitants residing at high altitude. By studying this unique population, which has adapted through natural selection, this study aimed to describe how humans can adapt to life with polycythaemia. Experimental studies included Andeans with (n = 19) and without (n = 17) chronic mountain sickness, documenting exercise capacity and characterizing the transport of oxygen through blood rheology, including haemoglobin mass, blood and plasma volume and blood viscosity, cardiac output, blood pressure and changes in total and local vascular resistances through pharmacological dissection of α-adrenergic signalling pathways within non-active and active skeletal muscle. At rest, Andeans with chronic mountain sickness had a substantial plasma volume contraction, which alongside a higher red blood cell volume, caused an increase in blood viscosity yet similar total blood volume. Moreover, both morphological and functional alterations in the periphery normalized vascular shear stress and blood pressure despite high sympathetic nerve activity. During exercise, blood pressure, cardiac work and global oxygen delivery increased similar to healthy Andeans but were sustained by modifications in both non-active and active skeletal muscle vascular function. These findings highlight widespread physiological adaptations that can occur in response to polycythaemia, which allow the maintenance of exercise capacity.

The vascular response to acute hyperglycaemia: What is the role of exercise capacity?

The vascular response to acute hyperglycaemia: What is the role of exercise capacity?

Acute Myocardial Infarction With Polycythemia Vera: A Rare Case

Introduction: Polycythemia Vera (PV) is one of the chronic myeloproliferative disorders that is rarely found, with a prevalence according to WHO around 2.3/100,000 inhabitants. The complication of PV is thrombosis, bleeding, and transformation into leukemia. Coronary events are common during the course of PV, approximately 11.4 % of patients had a myocardial infarction. Case: A 65-year-old male presented with complaints of chests pain accompanied by cold sweat, nausea, and vomiting. There was no organomegaly. Laboratory results showed Hb 23.2g/dL, HCT 72.1%, RBC 9.4 x106/uL, WBC 21,000/?L, PLT 470,000/uL. CKMB 56.1 U/L, Troponin T 1,751 pg/mL. ECG examination showed: ST elevation in lead V2-V4. The molecular result obtained the positive mutation of JAK2V617F. Discussion: Polycythemia Vera, in this case, was diagnosed based on the 2008 WHO criteria, which consisted of major criteria such as Hb> 18.5 g/dl in males and an increase in red blood cell volume; and the presence of JAK2V617F mutation, while Acute myocardial infarction (AMI) diagnosis in this case was based on the elevation of cardiac markers and ECG result. Acute myocardial infarction in PV was largely due to high RBC mass which increased blood viscosity. Conclusion: This patient was diagnosed with polycythemia vera and acute myocardial infarction based on clinical examination, laboratory results, and ECG. One of the aims of good management in PV is reducing cardiovascular events which is the main cause of morbidity and mortality.

Relationship Between Blood Viscosity and No-Reflow Phenomenon in St-Segment Elevation Myocardial Infarction Performed in Primary Percutaneous Coronary Interventions

Background: This study aimed to analyze the associations between no-reflow (NR) phenomenon development and whole-blood viscosity in patients with ST-elevated myocardial infarction. Methods: A total of 217 patients with ST-elevated myocardial infarction were included. whole-blood viscosity values were assessed using hematocrit and total protein values, and low shear rate (LSR) and high shear rate (HSR) were calculated. Results: The average LSR and HSR values of the study group were significantly higher than the control group (p<0.001). Multivariate logistic regression analysis showed that both HSR (odds ratio: 4.957; p<0.001) and LSR (odds ratio: 1.114; p<0.001) were independent predictors for NR development. Conclusion: This study found that increased blood viscosity was an independent predictor for NR development.

Flow Dynamic Analysis by Contrast-Enhanced Imaging Techniques of Medium Cutoff Membrane Hemodialyzer

Introduction: Medium cutoff (MCO) membranes represent an interesting innovation in the field of hemodialysis. Given the correlation between large (PM >25 kDa) middle molecules (LMM) and clinical outcomes, the possibility to broaden the spectrum of solutes removed in hemodialysis with MCO membranes introduces a new perspective for end-stage kidney disease patients. Due to low diffusion coefficients of LMM, the use of convection is required to maximize extracorporeal clearance. High convective rates are achieved with high-flux membranes in hemodiafiltration, a technique not available in the US. In case of the MCO membrane, remarkable clearances of LMM are achieved combining the permeability of the membrane with a significant amount of internal convection. The mechanism of filtration-backfiltration inside the dialyzer enables effective removal of LMM in a technique called expanded hemodialysis (HDx). Given such theoretical explanation, it is important to demonstrate the blood and ultrafiltration rheology inside the MCO dialyzer. Method: This study for the first time describes flow dynamic parameters and internal cross-filtration, thanks to specific radiology and nuclear imaging techniques. Results: Flow dynamic analysis of the blood and dialysate compartment confirms excellent distribution of velocities and an excellent matching of blood and dialysate. Average blood flow velocity allows for wall shear rates adequate to avoid protein stagnation at the blood membrane interface and increase in blood viscosity. Cross-filtration analysis demonstrates a remarkable filtration/backfiltration flux reaching values >30 mL/min at a blood flow of 300 mL/min and zero net filtration. Conclusion: The MCO dialyzer Theranova 400 appears to have a design optimized to perform expanded hemodialysis (HDx).

Compensatory depression of arterial pressure and reversal of ECG abnormalities by Annona muricata and Curcuma longa in hypertensive Wistar rats.

Increasing hypertension incidence in Sub-Sahara Africa and the current cost of management of the metabolic disorder has necessitated research on medicinal plants employed in African Traditional Medicine for hypertension. Thus, this study evaluated antihypertensive effect of Annona muricata leaves or Curcuma longa rhizomes in experimentally-induced hypertensive male Wistar rats (n=70) which were unilaterally nephrectomized and daily loaded with 1% salt. Cardiovascular and haematological changes, as well as urinalysis were determined. Rats were uninephrectomized and NaCl (1%) included in drinking water for 42days. Extract-treated hypertensive rats were compared to normotensive, untreated hypertensive and hypertensive rats treated with lisinopril (5mg/70kg) or hydrochlorothiazide (12.5mg/70kg). A.muricata extract or C.longa extract were administered at 100, 200 or 400mg/kg. Blood pressure (systolic, diastolic and mean arterial) and electrocardiogram was measured on day 41. Twenty-four-hour urine samples were collected from day 42. Blood samples were collected on day 43 for haematology (PCV, red cell indices, WBC and its differentials, and platelets). A.muricata or C.longa extracts caused a decline in elevated blood pressure of hypertensive rats. Heart rate and QT segment reduction coupled with prolonged QRS duration were reversed in extract-treated rats, with significant increases in hemogram parameters indicating increased blood viscosity. Also, leukocyturia, proteinuria and ketonuria with increased urine alkalinity, urobilinogen and specific gravity which are classical indicators of poor prognostic outcomes in hypertension were reversed in extract-treated rats. In conclusion, A.muricata and C.longa have cardioprotective effect with reversal of derangements in haemogram and urinalysis associated with hypertension.

Tam Kan Akışkanlığı ile Alt Ekstremite Periferik Arter Hastalığı Şiddeti Arasındaki İlişki

Aim: Increased blood viscosity (BV) has good correlaton with lower extremity peripheral artery disease (LEAD). However, the relationship between BV and peripheral arterial disease (PAD) severity has not been studied adequately so far. The aim of the present study was to assess the relationship between whole blood viscosity (WBV) and LEAD severity. Methods: The study included 240 consecutive patients with suspected PAD who had lower extremity peripheral angiography between March 2016 and March 2020. A Transatlantic İntersociety Consensus II (TASC II) A-B lesion was defined as simple LEAD, and a TASC II C-D lesion was defined as prevalent and complex LEAD. Symptom severity of all patients were categorized from 0 to 6 according to Rutherford classification. WBV was assessed using a validated calculation formula derived from hematocrit and total plasma protein levels, both at low (LSR) and high (HSR) shear rate. Results: TASC II C-D group presented significantly higher WBV values both at LSR (40.2 ± 9.5 vs. 46.5 ± 13.2; p &amp;lt; 0.001) and HSR (15.9 ± 0.5 vs. 16.5 ± 0,7; p &amp;lt; 0.001). In ROC analysis, a cut-off value of 16.1 WBV at HSR had 73.4% sensitivity and 68.0% specificity for predicting TASC II C-D (AUC: 76.2%, p &amp;lt; 0.001) and a cut-off value of 42.9 WBV at LSR had 73.4% sensitivity and 66.6% specificity for predicting TASC II C-D (AUC: 74.2%, p &amp;lt; 0.001). In multivariate analysis, both high WBV at LSR (OR: 2.121, 95% CI: 1.079 – 3.164, p &amp;lt; 0.001) and high WBV at HSR (OR: 2.737, 95% CI: 1.671 – 4.483, p &amp;lt; 0.001) were independent predictors for TASC II C-D. There was a significant positive correlation between WBV at LSR and Rutherford symptom category (0-6) (r = 0.412, p &amp;lt;0.001) and WBV at HSR and Rutherford symptom category (0-6) (r = 0.402, p &amp;lt;0.001). Conclusion: Our data suggests that; increased WBV values may be associated with TASC II C-D lesions, which indicated more prevalent and complex LEAD. Also WBV values positively correlated with Rutherford symptom severity.

Brain injury pathophysiology study by a multimodal approach in children with sickle cell anemia with no intra or extra cranial arteriopathy

Despite its high prevalence in children with sickle cell anemia (SCA), the pathophysiology of silent cerebral infarcts (SCI) remains elusive. The main objective of this study was to explore the respective roles of major determinants of brain perfusion in SCA children with no past or current history of intracranial or extracranial vasculopathy. We used a multimodal approach based notably on perfusion imaging arterial spin labeling (ASL) magnetic resonance imaging (MRI) and near infra-red spectroscopy (NIRS), as well as biomarkers reflecting blood rheology and endothelial activation. Out of 59 SCA patients (mean age 11.4±3.9 yrs), eight (13%) had a total of 12 SCI. Children with SCI had a distinctive profile characterized by decreased blood pressure, impaired blood rheology, increased P-selectin levels, and marked anemia. Although ASL perfusion and oximetry values did not differ between groups, comparison of biological and clinical parameters according to the level of perfusion categorized in terciles showed an independent association between high perfusion and increased sP-selectin, decreased red blood cell deformability, low hemoglobin F level, increased blood viscosity and no -thalassemia deletion. NIRS measurements did not yield additional novel results. Altogether, these findings argue for early MRI detection of SCI in children with no identified vasculopathy and suggest a potential role for ASL as an additional screening tool. Early treatment targeting hemolysis, anemia and endothelial dysfunction should reduce the risk of this under diagnosed and serious complication.

A Comparative Analysis of Erythropoietin and Carbamoylated Erythropoietin Proteome Profiles.

In recent years, erythropoietin (EPO) has emerged as a useful neuroprotective and neurotrophic molecule that produces antidepressant and cognitive-enhancing effects in psychiatric disorders. However, EPO robustly induces erythropoiesis and elevates red blood cell counts. Chronic administration is therefore likely to increase blood viscosity and produce adverse effects in non-anemic populations. Carbamoylated erythropoietin (CEPO), a chemically engineered modification of EPO, is non-erythropoietic but retains the neurotrophic and neurotrophic activity of EPO. Blood profile analysis after EPO and CEPO administration showed that CEPO has no effect on red blood cell or platelet counts. We conducted an unbiased, quantitative, mass spectrometry-based proteomics study to comparatively investigate EPO and CEPO-induced protein profiles in neuronal phenotype PC12 cells. Bioinformatics enrichment analysis of the protein expression profiles revealed the upregulation of protein functions related to memory formation such as synaptic plasticity, long term potentiation (LTP), neurotransmitter transport, synaptic vesicle priming, and dendritic spine development. The regulated proteins, with roles in LTP and synaptic plasticity, include calcium/calmodulin-dependent protein kinase type 1 (Camk1), Synaptosomal-Associated Protein, 25 kDa (SNAP-25), Sectretogranin-1 (Chgb), Cortactin (Cttn), Elongation initiation factor 3a (Eif3a) and 60S acidic ribosomal protein P2 (Rplp2). We examined the expression of a subset of regulated proteins, Cortactin, Grb2 and Pleiotrophin, by immunofluorescence analysis in the rat brain. Grb2 was increased in the dentate gyrus by EPO and CEPO. Cortactin was induced by CEPO in the molecular layer, and pleiotrophin was increased in the vasculature by EPO. The results of our study shed light on potential mechanisms whereby EPO and CEPO produce cognitive-enhancing effects in clinical and preclinical studies.